SURGICAL INFECTIONS Volume 16, Supplement 1, 2015 ª Mary Ann Liebert, Inc. DOI: 10.1089/sur.2015.9982.abstracts
PROGRAM AND ABSTRACTS Thirty-ﬁfth Annual Meeting of the Surgical Infection Society
Westlake Village, California April 15–18, 2015 Accreditation Statement This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education through the joint providership of the American College of Surgeons and the Surgical Infection Society. The American College Surgeons is accredited by the ACCME to provide continuing medical education for physicians. AMA PRA Category 1 Credits The American College of Surgeons designates this live activity for a maximum of 21 AMA PRA Category 1 Credits. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Disclosure Information Paragraph In compliance with ACCME Accreditation Criteria, the American College of Surgeons, as the accredited provider of this activity, must ensure that anyone in a position to control the content of the educational activity has disclosed all relevant financial relationships with any commercial interest. All reported conflicts are managed by a designated official to ensure a bias-free presentation. Please see the insert to this program for the complete disclosure list. Learning Objective: This activity is designed for physicians, research scientists, nurses, nurse practitioners, and pharmacists. Learning Objective(s)–At the end of this activity, participants will be able to: Summarize results on the latest research relevant to the diagnosis and treatment of surgical infections Use antimicrobials for empiric treatment of sepsis in trauma patients Debate current controversies in the diagnosis and treatment of surgical infections Use antimicrobials for a set course in the treatment of surgical infections Discuss recent developments in the study of cellular and molecular mechanisms in the pathogenesis of surgical infections Understand current treatment for secondary bacterial peritonitis
American College of Surgeons, Division of Education
Wednesday, April 15, 2015 19:00–21:30
Presidential Dinner (By invitation)
Thursday, April 16, 2015 06:30–07:30
Executive Council Breakfast (By invitation)
Executive Council Meeting (By invitation)
SURGICAL INFECTION UPDATE SYMPOSIUM
07:30–07:45 07:45–08:00 08:00–08:15 08:15–08:30 08:30–09:45
BIOLOGY OF SEPSIS and PHARMACOLOGY Microbiology of surgical pathogens: Gram-positive cocci Biology and metabolism of sepsis Organ physiology and multiple organ failure/dysfunction Antimicrobials and antibiotic PDs: Anti-staphylococcal drugs Q and A session
Lena Napolitano Matthew Rosengart John Marshall Pamela Lipsett
08:45–09:05 09:00–09:15 09:15–09:30 09:30–09:45 09:45–10:00
RISK PREVENTION/PROPHYLAXIS New intra-abdominal infection guidelines Clostridium difficile infections Antibiotic stewardship Q and A session BREAK
John Mazuski Brian Zuckerbraun Robert Sawyer
SPECIFIC INFECTIONS Necrotizing soft tissue infections DEBATE: Acute cholecystitis: Operate? Drain percutaneously? Soumitra Eachempati vs. Saman Arbabi DEBATE: Acute diverticulitis: Lavage or resect? Anastomose or divert? Lillian Kao vs. Christine Cocanour DEBATE: Acute appendicitis: Antibiotics or appendectomy? Therese Duane vs. E. Patchen Dellinger Q and A session
Nominating Committee (By invitation)
LUNCHEON SYMPOSIUM (Industry-sponsored; not part of scientific program)
PLENARY SYMPOSIUM The Art and Science of Surgical Infections (Papers 1–10) Moderators: Nicholas Namias, MD, MBA, and John C. Alverdy, MD
10:00–10:15 10:15–10:35 10:35–10:55 10:55–11:15
O1. Pathway Analysis of the Intestinal Transcriptome of Mice Rescued from Sepsis via a Fecal Microbiota Transplant Demonstrates a Role for IL22. Monika Krezalek (Resident), presenting. University of Chicago. Discussant: Michaela West, MD, PhD O2. Statewide Evaluation of Intra-wound Antibiotics in Spine Surgery Patients: A Report from the SCOAP-CERTAIN Collaborative. Anne Pugel, (Resident) presenting. University of Washington. Discussant: Robert G. Sawyer, MD O3. Microbial Changes in Opioid-Induced Colonic Anastomotic Leak. Baddr Shakhsheer (Resident), presenting. University of Chicago. Discussant: Philip S. Barie, MD, MBA O4. Colonic Lavage for the Treatment of Severe C. difficile Infections: The London Protocol. Kalvin Lung, (Resident) presenting. University of Western Ontario. Discussant: Pamela A. Lipsett, MD, MHPE O5. Hepatocytes Are a Dominant Source Of HMGB1 in the Innate Immune Response During Sepsis. Meihong Deng, (New Member) presenting. University of Pittsburgh. Discussant: Henri R. Ford, MD, MHA O6. Obesity Is Not Associated with Antimicrobial Treatment Failure for Intra-Abdominal Infection. Zachary Dietch (Resident), presenting. University of Virginia. Discussant: E. Patchen Dellinger, MD O7. Deficiency in Oncostatin M Receptor Results in Improved Survival in Older Mice Following Sepsis Through Down-Regulation of IL-10. Saad Salim (New Member), presenting. University of Alberta. Discussant: Brian Zuckerbraun, MD O8. Novel Predictors of Burn Wound Infections in Severely Burned Children. Arham Ali (Resident), presenting. University of Texas Medical Branch. Discussant: Basil A. Pruitt, Jr., MD O9. Repair of the Enteric Nervous System through Vagal-Mediated Expansion of Neural Stem Cells. Simone Langness (Resident), presenting. University of California, San Diego. Discussant: William G. Cheadle, MD O10. Risk-Adjustment for Determining Surgical Site Infection in Colon Surgery: Are We Using Appropriate Variables? Sydne Muratore, presenting. University of Minnesota. Discussant: Donald E. Fry, MD
SIS Antibiotic Duration Study-Robert G. Sawyer, MD
Surgical Infections Editorial Reception (By Invitation)
SIS Foundation Board Meeting (By Invitation)
Waterfall Friday, April 17, 2015
Breakfast Symposium (Industry-sponsored; not part of scientific program)
PARALLEL SESSION I Clinical Research (Papers 11–15) Moderators: Daithi S. Heffernan, MD, and Sandra Swoboda, RN, MSN
O11. RibScore: A Novel Radiographic Score Based on Fracture Pattern that Predicts Pneumonia, Respiratory Failure, and Tracheostomy. Brandon Chapman (Resident), presenting. University of Colorado-Denver. Discussant: Addison K. May, MD O12. Top Guns: The Maverick and Goose of Empiric Therapy. Stephen Davies (Resident), presenting. University of Pittsburgh. Discussant: Jeffrey L. Johnson, MD O13. Contact Isolation in Trauma Patients: An Analysis of Infectious Complications. Mark Hamill, presenting. University of Virginia. Discussant: Sandra M. Swoboda, MSN, RN O14. Comparing Readmissions and Infectious Complications of Blunt Splenic Injuries Using a Statewide Database. Olubode Olufajo presenting. Brigham and Women’s Hospital. Discussant: Daithi S. Heffernan, MD O15. Impact of Type of Insurance on Infection Rates after Trauma. Jaswin Sawhney (Resident), presenting. Brown University. Discussant: Amy A. McDonald, MD
PARALLEL SESSION II Basic Science (Papers 16–20) Moderators: Carl Hauser, MD and Brian Eliceiri, PhD
O16. Hypothermia Prolongs the Survival of Rats with Severe Septic Shock by Inhibiting the Splenic Release of Neutrophils and Monocytes. Rhett N. Willis (Resident), presenting. University of Virginia. Discussant: Kevin P. Mollen, MD O17. Listeria monocytogenes Inhibits Th17 Responses Through TLR2 Signaling. Song Liu, presenting. Medical School of Nanjing University. Discussant: Meihong Deng, MD O18. Mitochondrial ROS Induces Cardiac Inflammation via Damage in Mitochondrial DNA and Stimulation of RAGE Pathway in a Pneumonia-related Sepsis Model. Qun (Sophia) Zang, presenting. University of Texas- Southwestern. Discussant: Carl Hauser, MD O19. Blue Light Reduces Organ Injury During Critical Illness. Du Yuan (Resident), presenting. University of Pittsburgh. Discussant: Nicholas Namias, MD, MBA O20. The Collagenolytic Activity of Fecal Enterococcus faecalis Predicts Anastomotic Leak: Development of a Novel Assay to Clinically Track the Collagenolytic Phenotype. Kristina Guyton (Resident), presenting. University of Chicago. Discussant: Matthew R. Rosengart, MD, MPH
BREAK-Visit the Exhibits
William A. Altemeier Memorial Lecture ‘‘Evolving Epidemiology of MOF into PICS’’ Frederick A. Moore, MD, FACS, MCCM Professor and Chief of Acute Care Surgery, University of Florida Health
Surgical Infection Society Presidential Address ‘‘Let’s Go Far’’ John C. Alverdy, MD The Sara and Harold Lincoln Thompson Professor and Executive Vice Chair Department of Surgery, University of Chicago Medicine
LUNCHEON SYMPOSIUM (Industry-sponsored; not part of scientific program)
UPDATE SYMPOSIUM I International Topics in Surgical Infections Moderator: Joseph Solomkin, MD
Topic 1: Strategies to Prevent SSI in Japan
Topic 2: Approach to Surgical Site Infection in Nicaragua
Topic 3: Surgical Infections in the Deployed Setting
Topic 4: Surgical Site Infection Rates following Cesarean Section in Sub-Saharan Africa: A Focus Point for Guideline-Based Intervention
Break-Visit the Exhibits
PARALLEL SESSION III Clinical Research (Papers 21–26) Moderators: Samir S. Awad, MD and Heather L. Evans, MD, MS
O21. Preoperative Antisepsis Protocol Compliance and the Effect on Bacterial Load Reduction. Alison Smith (Resident), presenting. Tulane University. Discussant: Jared Huston, MD O22. Necrotizing Enterocolitis: Does Perforation Matter? Varun Bhalla, presenting. Children’s National Medical Center. Discussant: Catherine J. Hunter, MD O23. Abdominal Compartment Syndrome, Cerebral Infarction, and Acute Respiratory Distress Syndrome Are the Biggest Modifiable Risk Factors for Surgical Site Infections in Blunt Traumatic Hemorrhagic Shock. John Hwabejire (Resident), presenting. Howard University. Discussant: Lena M. Napolitano, MD O24. Do Polymicrobial Intra-Abdominal Infections Have Worse Outcomes than Monomicrobial Intra-Abdominal Infections? Puja M. Shah (Resident), presenting. University of Virginia. Discussant: Lillian Kao, MD O25. The Influence of Beta-Lactam Prescribing Patterns on Resistance Rates among Various Adult ICU Populations. Sara E Parli, presenting. University of Kentucky. Discussant: Jeffrey M. Tessier, MD O26. Prophylactic Gentamicin Is Not Associated with Acute Kidney Injury in Patients with Open Fractures. Jeffrey M. Tessier, presenting. JPS Health Network. Discussant: Heather L. Evans, MD, MS S-5
PARALLEL SESSION IV Basic Science (Papers 27–32) Moderators: Matthew R. Rosengart, MD, MPH and Todd W. Costantini, MD
O27. Paucity of Bacteria Implicated in Pathogenesis of Experimental Necrotizing Enterocolitis. Joanna Lim (Resident), presenting. Children’s Hospital Los Angeles. Discussant: Michael J. Morowitz, MD O28. Pre-B Cell Colony Enhancing Factor (PBEF)/Nampt Phosphorylation by PI3 Kinase Is Indispensable for the Inhibition of Neutrophil (PMN) Apoptosis in Patients with Sepsis. Song Jia (New Member), presenting. Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, Toronto. Discussant: John Mazuski, MD, PhD O29. Acute Appendicitis in Children is Associated with an Abundance of Bacteria from the Genus Fusobacterium. Matthew Rogers (New Member), presenting. Children’s Hospital of Pittsburgh. Discussant: Jose J. Diaz, MD O30. Effect of Remote Ischemic Preconditioning on LPS-Induced Pulmonary Inflammation in Mice. So Jung Choi (New Member), presenting. University of Toronto. Discussant: Brian Eliceiri, PhD O31. Latent Cytomegalovirus Infection Predisposes Immune Competent Hosts to Pro-Inflammatory Pulmonary Immune Responses. Varun Dwivedi, presenting. The Ohio State University. Discussant: Ori Rotstein, MD O32. Defining the Mitochondrial DAMP Repertoire: Formyl Peptides Are Not All Created Equal! Carl Hauser, presenting. Center for Vascular Biology Research, Harvard Medical School, BI Deaconess Medical Center. Discussant: Gary C. An, MD
Annual Business Meeting (Members only)
Saturday, April 18, 2015 07:00–08:00
Executive Council Meeting (By invitation)
UPDATE SYMPOSIUM II Ballroom BCD What to Do with the Darned Sub-specialists: Common Practices in Surgical Infections Moderator: Jeffrey Claridge, MD
Topic 1: Thoracic Surgery Topic 2: Orthopedic Surgery
Daniel Raymond Antonia Chen
UPDATE SYMPOSIUM III PRO-CON DEBATES Moderator: John Mazuski, MD, PhD DEBATE: Nutritional Support: Does It Matter? Patricia Byers vs. Michael Morowitz DEBATE: Fever-Suppress or Let It Ride? Carl Schulman vs. Kaysie Banton
FELLOWSHIP AWARD RECIPIENT PRESENTATIONS Moderators: Philip S. Barie, MD, MBA and Kevin P. Mollen, MD S-6
SIS Foundation Basic or Translational Research Training Fellowship-2014 Anthony J. Lewis, MD. University of Pittsburgh SIS Foundation Clinical Research Training Fellowship-2014 Elinore J. Kaufman, MD. Weill Medical College of Cornell University SIS Foundation Junior Faculty Fellowship-2014–2015 Heather L. Evans, MD, MS. University of Washington 10:15–10:30
BREAK–Visit the Exhibits
PARALLEL SESSION V Clinical Research (Papers 33–38) Moderators: Mary R. Kwaan, MD, MPH and David P. Blake, MD, MPH
O33. Does Circadian Rhythm Affect the Risk for Post-Operative Infectious Complications? Christopher Guidry (Resident), presenting. University of Virginia. Discussant: Christine S. Cocanour, MD O34. WITHDRAWN O35. Obesity Paradox in Patients with Soft Tissue Infections Nationwide. Elissa Lin, presenting. Brigham and Women’s Hospital. Discussant: David P. Blake, MD, MPH O36. Developing an SSI Risk Score Incorporating Daily Objective Wound Assessments Using Machine Learning. Heather L. Evans, presenting. University of Washington. Discussant: Donald E. Fry, MD O37. Component Separation versus Bridged Repair for Large Ventral Hernias: A Multi-Institutional Risk-Adjusted Comparison. Julie Holihan (Resident), presenting. University of Texas Health Science Center at Houston. Discussant: Kamal M. F. Itani, MD O38. Clinical Diagnosis of Infection in SICU: You Are Not as Good as You Think! Madhu Subramanian (New Member), presenting. University of Texas, Southwestern. Discussant: Patrick J. O’Neill, PhD, MD
PARALLEL SESSION VI Basic Science (Papers 39–43) Moderators: Gary C. An, MD and Rachel Khadaroo, MD, PhD
O39. Characterization of the Murine Septic Response Using Wireless Telemetry Technology. Anthony Lewis (Resident), presenting. University of Pittsburgh. Discussant: Tina S. Mele, MD O40. Lactobacillus Probiotic Species Strengthen Intestinal Barrier Function and Tight Junction Integrity. Brian Blackwood (Resident), presenting. Northwestern University Feinberg School of Medicine. Discussant: John Marshall, MD O41. Mesenchymal Stem Cells Reverse Anemia and Bone Marrow Dysfunction Following Trauma, Hemorrhagic Shock, and Chronic Stress. Amy Gore (Resident), presenting. Rutgers-New Jersey Medical School. Discussant: Todd W. Costantini, MD
O42. Remote Ischemic Preconditioning Plasma Prevents Neutrophil Infiltration by Increased Anti-oxidative Capacity in the Zebrafish. Chung Ho Leung, presenting. University of Toronto. Discussant: Brian Zuckerbraun, MD O43. Pseudomonas aeruginosa Infection Augments Burn-Induced Hepatic ER Stress. Mile Stanojcic´ (Resident), presenting. Sunnybrook Research Institute, University of Toronto, Toronto, Canada. Discussant: Steven E. Wolf, MD
LUNCHEON SYMPOSIUM (Industry-sponsored; not part of scientific program)
PARALLEL SESSION VII: The Surgical Infection Society-Supreme Court (Papers 44–48) Ballroom BCD Moderators: Pamela A. Lipsett, MD, MHE, John C. Alverdy, MD, John C. Marshall, MD, Robert G. Sawyer, MD, and William G. Cheadle, MD
O44. Computed Tomography Versus Ultrasound for the Diagnosis of Acute Cholecystitis. D. Dante Yeh, presenting. Harvard Medical School, Massachusetts General Hospital. O45. Comparison of Screening Tools’ Ability to Detect Sepsis Accurately. Richard Wawrose, presenting. University of Texas Health Science Center at Houston. O46. Pulmonary Microbiome and Cytokine Analysis of Bronchoalveloar Lavage in Mechanically Ventilated Trauma Patients? Ryan M. Huebinger, presenting. University of Texas Southwestern. O47. The Transition from a Rural to Urban Environment in Africa Alters the Expression of Genes Involved in Cholesterol Metabolism: Potential Implications for Susceptibility to Infectious Diseases. Radhames Lizardo, presenting. University of California, San Diego. O48. Impact and Progression of Organ Dysfunction in Patients with Necrotizing Soft Tissue Infections; A Multicenter Study. Eileen M. Bulger, presenting. University of Washington.
POSTER SESSION (Posters 1–52) Basic and Clinical Studies in Surgical Infection
Group 1: Cell Biology 1 (P1–P6) Michael Cripps, MD and Catherine J. Hunter, MD Group 2: Cell Biology II (P7–P11) Kevin P. Mollen, MD and Celeste C. Finnerty, PhD Group 3: Outcomes I (P12–P17) Patrick J. O’Neill, PhD, MD and Michael K. Liang, MD Group 4: Outcomes II (P18–P23) Soumitra R. Eachempati, MD and Charles A. Adams Jr., MD Group 5: Pathogens I (P24–P29) Jeffrey W. Shupp, MD and Barbara Trautner, MD, PhD Group 6: Pathogens II (P30–P35) Howard Belzberg, MD and Philip Chang, MD Group 7: Wounds and Incisions I (P36–P40) Christine S. Cocanour, MD and Jose J. Diaz, MD Group 8: Wounds and Incisions II (P41–P45) Weidun Alan Guo, MD and Kamal M. F. Itani, MD
New Member Reception
Oral Presentation Abstracts
O01. PATHWAY ANALYSIS OF THE INTESTINAL TRANSCRIPTOME OF MICE RESCUED FROM SEPSIS VIA A FECAL MICROBIOTA TRANSPLANT DEMONSTRATES A ROLE FOR IL-22 Monika Krezalek, Jennifer DeFazio, Sangman Kim, Nikolai Khodarev, Alexander Zaborin, Scott Christley, Baddr Shakhsheer, Kristina Guyton, Bana Jabri, Olga Zaborina, John Alverdy, The University of Chicago Background: Post-surgical sepsis due to hospital acquired pathogens (PSS-HAP) is one of the most common causes of death in the surgical ICU. We recently demonstrated that PSS-HAP pathogenesis is driven by a critical loss of the intestinal ‘‘microbiome’’ leading to systemic immune dysregulation and mortality which can be reversed by a fecal microbiota transplant (FMT). Hypothesis: Here we hypothesize that the rescue effect of FMT is mediated in part by its ability to suppress IL-22. Methods: We modeled lethal gut-derived sepsis using mice subjected to a 30% hepatectomy followed by cecal inoculation with HAPs consisting of a multi-drug resistant human pathogen community isolated from the stool of a septic ICU patient. Mice showing signs of sepsis on POD1 were administered a fecal microbiota transplant (FMT) consisting of homogenized pooled mouse cecal contents versus control material consisting of autoclaved (AC) pooled cecal contents. Whole-genome transcriptional profiling was performed on cecal tissues using Illumina MouseRef-8 v2 arrays with functional analysis of differentially expressed genes using Ingenuity pathway analysis and DAVID software. Results: In the control AC group we noted systemic activation of pathways associated with adaptive and innate immunity, including TLR4/Myd88-dependent pro-inflammatory pathways. These pathways were significantly associated with over-expression of up-stream pro-inflammatory mediators: IL-1ß (13-fold), TNF-a (43-fold) and IL-17A (60-fold). We also noted increased expression of STAT3 (2.5-fold) and its downstream target genes (up to 140-fold). Treatment by FMT led to significant attenuation of these pathways on POD2 compared to AC. Given that STAT3 controls IL-22 expression and given the known relationship of IL-22 production to TLR4 signaling, we directly assayed IL-22 in these experiments via ELISA and qRT-PCR and observed that FMT suppresses IL-22 production compared to AC controls (2.5- and 8-fold reduction via ELISA and qRT-PCR respectively p < 0.01). In order to determine the role of IL-22 in the FMT-mediated rescue effect, we treated septic mice with anti-IL22 antibody on POD1 and observed a significant reduction in mortality (AC = 73%, anti-IL-22 = 40%, p < 0.01), although FMT provided the lowest mortality (13%; p < 0.001, n = 15/group). Conclusions: Taken together, these studies suggest that FMT can rescue mice from severe post-surgical sepsis due to hospital-acquired pathogens via mechanisms involving, in part, IL-22 expression.
O02. STATEWIDE EVALUATION OF INTRA-WOUND ANTIBIOTICS IN SPINE SURGERY PATIENTS: A REPORT FROM THE SCOAP-CERTAIN COLLABORATIVE Anne Pugel, Sara Khor, Neal Shonnard, Rod Oskouian, Jr., Rajiv Sethi, Amy Cizik, Michael Lee, Samuel Bederman, E. Patchen Dellinger, David Flum, University of Washington Background: Surgical site infection (SSI) after spine surgery is classified as a never event but occurs up to 10% of the time, often with devastating consequences. Intrawound antibiotics (IWA) have been proposed to reduce the incidence of spine SSI. Robust evidence to support IWA use is lacking. Hypothesis: We hypothesize that rates of SSI will differ between patients who did and did not receive IWA. Methods: We evaluated IWA use in a prospective cohort undergoing spine fusion surgery at 20 Washington State hospitals ( July 2011-March 2014) participating in the Surgical Care and Outcomes Assessment Program Spine Program (Spine SCOAP). Patient, hospital, and operative covariates associated with SSI and IWA use during index hospitalizations were analyzed. Effects of IWA on SSI were examined using a random effects logistic model adjusting for patient and hospital characteristics. A pro-
pensity score-matching analysis was also performed independently to confirm our findings. Results: 9,646 cervical or lumbar fusions were completed during the study period (mean age 58 y, 90% white, 54% female). Nearly all (99%) received antibiotics on time, and 97% were normothermic in the recovery room. Overall, the infection rate was 1.1%. Those with SSI were more likely to be non-white (22% vs. 13%, p < 0.01), older (64 vs. 58 years, p < 0.01), to have diabetes mellitus (32% vs. 17%, p < 0.01), and more frequently underwent lumbar versus cervical fusion (76% vs 52%, p < 0.01). The unadjusted rate of SSI was 0.8% for those who received IWA and 1.5% for those who did not (OR: 0.56; p < 0.01). The use of IWA varied widely across hospitals (10%-98.2%, p < 0.01), but increased use of IWA was not correlated to SSI (r2 = 0.16). In the randomeffects logistic model clustering by hospital, those who received IWA had similar odds of SSI (OR 0.7, 95% CI 0.46-1.07; p = 0.097). A separate propensity score analysis demonstrated no significant difference in SSI between those who did and did not receive IWA (1.01% vs. 1.41%, p = 0.12). Conclusions: Whereas unadjusted analyses indicate a nearly 50% reduction in SSI using IWA, once multivariable adjustment of patient, provider, and hospital characteristics was used the rate of SSI was not significantly lower. It remains to be determined if IWA should be promoted as a quality improvement intervention. A large trial is needed to determine the effectiveness of this treatment. Nearly 32,000 subjects would be needed to study IWA effectively given the low incidence of SSI and am estimated 30% risk reduction.
O03. MICROBIAL CHANGES IN OPIOID-INDUCED COLONIC ANASTOMOTIC LEAK Baddr Shakhsheer, James Luo, Scott Christley, Jennifer DeFazio, Robin Klabbers, Kristina Guyton, Monika Krezalek, Natalia Belogortseva, Alexander Zaborin, Olga Zaborina, John Alverdy, University of Chicago Background: Opioid analgesics are ubiquitously used following gastrointestinal surgery and have many undesirable effects such as delayed intestinal transit, intestinal bacterial overgrowth, and increased incidence of surgical site infections. Previous work from our lab demonstrated that opioids can induce intestinal bacteria to express enhanced virulence against the intestinal epithelium. Hypothesis: Opioids alter anastomotic healing, leading to leakage via their effect on the intestinal microbiota-agents we have recently shown play a key and causative role in anastomotic leak. Methods: Rats underwent distal colectomy with anastomosis and were implanted with a slow-release morphine or placebo pellet in the subcutaneous neck. Rats were sacrificed on post-operative day six and autopsied for gross signs of anastomotic leak. Local anastomotic tissues were examined by high-magnification microscopy. Composition and function of microbial populations in anastomotic tissues was determined by 16S rRNA and PICRUST analyses. Recovered bacterial species were tested for collagenolytic activity. Results: Morphine-treated rats developed a *50% leak rate compared with a 3% leak rate in the placebo group. High-powered imaging of the anastomotic site showed visible disruption of the anastomoses with mucosal ulceration in the morphine group but not in placebo group. 16S rRNA analysis revealed a bloom in abundance of Escherichia/ Shigella (avg. 0.56% at POD0 vs. 32% at POD6) and Bacteroides (avg. 3.9% at POD0 vs. 24% at POD6) in both placebo and morphine post-operative groups. PICRUST analysis predicted a shift of microbial population metabolism at POD6 to synthesis of lipopolysaccharides, sphingolipid and lipoic acid metabolism, leading to production of bioactive signaling lipid molecules involved in the apoptosis and adhesion regulation. There were no significant differences in microbial composition and function in postoperative tissues between groups. Only Enterococcus faecalis and Proteus mirabilis were able to produce high collagenase activity in vitro. In all cases where both collagenase-producing E. faecalis and P. mirabilis were not recovered, there was no leak, suggesting them as critical players when in combination. Conclusions: Anastomotic leak in rats under morphine treatment is associated with colonization of anastomotic tissues by a pair of high-collagenase-producing strains of E. faecalis and P. mirabilis at the background of a profound distortion of microbial composition and function.
ORAL PRESENTATION ABSTRACTS
O04. COLONIC LAVAGE FOR THE TREATMENT OF SEVERE C. DIFFICILE INFECTIONS: THE LONDON PROTOCOL Kalvin Lung, Greig McCreery, Neil Parry, Daryl Gray, Chris Vinden, Ken Leslie, Tina Mele, University of Western Ontario Background: Severe Clostridium difficile infection (CDI) is associated with high mortality and may require subtotal colectomy. Based on encouraging results of colonic irrigation via ileostomy (‘‘Pittsburgh protocol’’ [PP]), we developed a non-invasive protocol of colonic irrigation via nasojejunal (NJ) tube (‘‘London protocol’’ [LP]) to use in poor surgical candidates with severe CDI. Our objective was to compare patient outcomes with these 2 treatment approaches. Hypothesis: We hypothesized that colonic lavage via the London Protocol is safe, effective treatment of severe CDI patients. Methods: This was a retrospective cohort study of consecutive CDI patients refractory to medical therapy referred for surgical consultation. In addition to antibiotics, the LP group received 8 L of polyethylene glycol over 48 h via NJ tube. The PP and LP were used at our tertiary hospital in the last 2 years. Consulting surgeons decided whether to use PP or LP and proceeded to colectomy if PP or LP had failed. Patients who went directly to colectomy over the last 5 years were used as a comparison group. Intention-to-treat analysis, Fisher exact test, and ANOVA were used. Results: Thirteen, 9 and 17 patients underwent LP, PP, and direct colectomy, respectively. There were no differences between groups with respect to age, gender, ASA class, ICU admission, vasopressor use, presence of peritonitis, hypotension, tachycardia, WBC > 20K or < 4K, mean lactate or creatinine at time of surgical consultation (all, p > 0.05). More PP patients failed and required colectomy compared to LP (5/9 vs. 1/13, p = 0.02). In-hospital mortality rates were 15% (2/13), 44% (4/9) and 41% (7/17) for the LP, PP, and direct colectomy groups, respectively (p = 0.26). Of the 2 mortalities in the LP group, both had early deviations from protocol. One patient had active care withdrawn by family the day after LP was initiated, and died that day. The second patient started LP at a delayed stage, could not tolerate NJ irrigation on the first day of LP and thus, had immediate colectomy and died within 48 h. Mortality rates, excluding these 2 deaths, were significantly lower in the LP group (p = 0.03). Conclusions: Colonic irrigation via NJ tube in the context of the LP appeared to be safe and effective in management of severe CDI. We found no significant differences in disease severity between groups. Per-protocol analysis shows mortality reduction with use of this approach. Intention-to-treat analysis shows that this approach does not lead to increased mortality.
O05. HEPATOCYTES ARE A DOMINANT SOURCE OF HMGB1 IN THE INNATE IMMUNE RESPONSE DURING SEPSIS Meihong Deng, Melanie Scott, Timothy Billiar, University of Pittsburgh Background: High-mobility group protein B1 (HMGB1) is a nucleus-DNA binding protein, which is secreted into extracellular milieu as an inflammatory cytokine during sepsis. However, the dominant source of circulating HMGB1 in sepsis is unknown. Hypothesis: We hypothesized that hepatocytes (HCs) are one important source of circulating HMGB1 during sepsis. Methods: To test the hypothesis, we generated HC-specific HMGB1-/- mice. C57BL/6 (WT), cell-specific knockout control (Flox), and hepatocyte-specific HMGB1-/- (HC-HMGB1-/-) mice underwent cecal ligation and puncture (CLP) for 18 h. Results: In WT mice, HMGB1 translocated from nucleus to cytoplasm in HC visualized by immunofluorescence staining with a dramatic increase of circulating HMGB1 level assessed by ELISA after CLP. Surprisingly, specific deletion of HMGB1 in HC resulted in more than 75% reduction in the plasma HMGB1 level (HC-HMGB1-/-: 11.8 – 3.3 ng/mL) compared to the control mice (WT: 59 – 7.3 ng/mL, Flox: 53 – 15.04 ng/mL) after CLP, suggesting that HC-HMGB1 was the major source of circulating HMGB1 during sepsis. Importantly, specific deletion of HMGB1 in HC significantly lowered bacterial load in peritoneum compared to controls (HC-HMGB1-/-: 7.0x105 – 6.0x105 vs. WT: 1x107 – 1.5x106 CFU/mL and Flox: 7.33x107 – 3.06x106CFU/ mL, p < 0.05) at 18 h after CLP, with a decrease in systemic inflammation indicated by significantly lower circulating IL-6 and IL-1b. Furthermore, fewer peritoneal apoptotic PMNs (Ly6G + ve, and TMR + ve cells) were detected by flow cytometry in HCHMGB1-/- (3.12 – 0.21%) mice than in control mice (WT: 8.43 – 0.67% and Flox: 6.98 – 0.53%). This correlated with the HMGB1 levels in peritoneal lavage fluid and inversely correlated with the bacterial load. These results suggested that the release of HMGB1 from HC might contribute to cell death in PMNs during sepsis. To test whether HC release HMGB1 actively or passively from necrotic process, liver histology and ALT levels were determined. No obvious necrotic areas were seen in liver section in any mice strain after CLP. ALT levels elevated after CLP; however no significantly difference was detected among the strains. It suggested that HMGB1 was not released passively from necrotic HCs. Conclusions: Together, these results suggest that HMGB1 released by HCs during sepsis may be an active process that regulates bacterial clearance via induction of cell death in peritoneal PMNs.
O06. OBESITY IS NOT ASSOCIATED WITH ANTIMICROBIAL TREATMENT FAILURE FOR INTRA-ABDOMINAL INFECTION Zachary Dietch, Puja M. Shah, Brandy Edwards, Stephen Davies, Guidry, Robert Sawyer, University of Virginia Health System
Background: Obesity and commonly associated comorbidities are known risk factors for the development of infections. However, the intensity and duration of antimicrobial treatment are rarely conditioned on body mass index (BMI). In particular, the influence of obesity on failure of antimicrobial treatment for intra-abdominal infection (IAI) remains unknown. Hypothesis: We hypothesized that obesity is associated with recurrent infectious complications in patients treated for IAI. Methods: 518 patients randomized to treatment in the Surgical Infection Society Study to Optimize Peritoneal Infection Therapy (STOP-IT) trial were evaluated. One patient was excluded from analysis because of missing data. Patients were stratified by obese (BMI ‡ 35 kg/m2) versus non-obese (BMI < 35) status. Descriptive comparisons were performed using Chi-square, Fisher exact, or Wilcoxon rank-sum tests as appropriate. Multivariable logistic regression using a priori selected variables was performed to assess the independent association between obesity and treatment failure in patients with IAI. Results: Overall, 100 (19.3%) of patients were obese (BMI ‡ 35) versus 417 (80.7%) who were non-obese. Mean antibiotic days and total hospital days were similar between groups. Unadjusted outcomes of surgical site infection (10.0% vs. 7.2%, p = 0.35), recurrent intra-abdominal infection (15.0% vs. 14.6%, p = 0.92), death (2.0% vs. 0.7%, p = 0.25), and a composite of all complications (25.0% vs. 21.0%, p = 0.40) were also similar between groups. After controlling for appropriate demographics, comorbidities, severity of illness, treatment group, and duration of antimicrobial therapy, obesity was not independently associated with treatment failure (c-statistic: 0.70) (Table). Conclusions: Obesity is not associated with antimicrobial treatment failure among patients with IAI. These results suggest that obesity may not independently influence the need for longer duration of antimicrobial therapy in treatment of IAI versus non-obese patients.
O07. DEFICIENCY IN ONCOSTATIN M RECEPTOR RESULTS IN IMPROVED SURVIVAL IN OLDER MICE FOLLOWING SEPSIS THROUGH DOWN-REGULATION OF IL-10 Nour AlMalki, Saad Salim, Thomas Churchill, Rachel Khadaroo, University of Alberta Background: Sepsis and septic shock are leading causes of multiple organ failure. The role of the anti-inflammatory response in sepsis is not clearly understood. Oncostatin M (OSM) is a novel cytokine part of the IL-6 cytokine family. It has been shown to increase during sepsis and recently was linked to influencing interlukin 10 (IL-10) levels in other disease processes. IL-10, a powerful endogenous anti-inflammatory cytokine, decreases the severity of inflammation by blocking recruitment of inflammatory cells to the site of injury. Hypothesis: To further understand OSM and IL-10’s role in sepsis, we used OSM receptor (OSMR) knockout mice. We hypothesized that OSMR deficiency regulates the inflammatory, and more specifically, the anti-inflammatory process during sepsis in older mice.
ORAL PRESENTATION ABSTRACTS Methods: Sepsis was induced in 50–70 wk mice via intra-peritoneal injection of cecal slurry (CS) at LD30 of 1.3 mg/mg. Mice were observed every 2 h for 18 h. Euthanasia and necropsy were performed. Cytokine levels in organ homogenates were measured using Meso Scale Discovery (MSD) multiplex. Results: 70% of the OSMR knockouts mice had died after 24 h of CS injection, while none of the WT mice did. Cytokine levels from tissue homogenates in the two groups showed IL-10 expression had remarkably decreased in OSMR-/- mice. Serum, lung and kidney homogenates of the CS-treated OSMR -/- group had significantly lower levels of IL-10 than WT. Although levels were not significant in peritoneal lavage and liver homogenates, they had the same trend of being lower in OSMR -/- than WT. Conclusions: OSMR deficiency results in attenuated lung and kidney IL-10 levels. That OSMR deficiency down-regulates the anti-inflammatory response is important in promoting survival in elderly mice following sepsis. Further understanding of the antiinflammatory response in sepsis will be beneficial in developing novel approaches to therapy.
S-11 barrier function, with increased intestinal permeability seen in vagotomized animals at 48 h post-injury compared to I/R alone. Conclusions: The ENSC population within the gut undergoes expansion following acute injury through a vagus-dependent pathway. Given that an intact ENS is required to maintain intestinal barrier function, augmenting repair of the ENS by stimulating or recruiting ENSC may result in improved kinetics of injury resolution.
O10. RISK-ADJUSTMENT FOR DETERMINING SURGICAL SITE INFECTION IN COLON SURGERY: ARE WE USING APPROPRIATE VARIABLES? Sydne Muratore, Catherine Statz, JJ Glover, Mary Kwaan, Greg Beilman, University of Minnesota
O08. NOVEL PREDICTORS OF BURN WOUND INFECTIONS IN SEVERELY BURNED CHILDREN Arham Ali, Hyunsu Ju, James Gwosdz, David Herndon, Celeste Finnerty, University of Texas Medical Branch/Shriner’s Hospital for Children Background: The ability to identify infections early during hospital admission following burn injury has been augmented by genomic and proteomic techniques. The aim of this study is to identify novel early predictors of gram negative or positive wound infections in children. Hypothesis: We hypothesize that early identification of gram-negative or -positive infections can be accomplished using serum markers. Methods: Data from 63 children (age < 18 y) with burns covering ‡ 30% of the total body surface area (TBSA) was analyzed in this study. The American Burn Association definition of burn wound infections (BWIs) was used: Wound biopsies growing > 105 bacteria/g of tissue with the identification of a pathogen. Pathogens were divided based on gram stain into gram-positive and gram-negative species. Cytokines, serum metabolites, and various clinical outcomes were identified as possible predictors of BWIs. Data were analyzed using a multivariable logistic regression model. Odds ratio estimates and Wald confidence intervals of each predictor were evaluated for statistical significance with a two-sided significance level of 0.05. Results: Average age at the time of burn injury was 9 – 5 y. Children endured large (64 – 16 %TBSA) and severe (56 – 21% TBSA 3rd) burns and were admitted on average at 2 – 1 d post = burn. Each child acquired 6 – 7 BWIs up until hospital discharge. Development of gram-positive BWI was significantly related to interleukins (IL)-1b and -7, cytokine G-CSF, transferrin, a1-acid glycoprotein, and hyperglycemia (p = 0.02, p = 0.02, p = 0.03, p = 0.01, p = 0.02, and p = 0.02 respectively). Conversely, IL-8, TNF-a, MIP-1b, complement factor C3, and total number of operationa were significantly associated with BWI from gram-negative bacteria (p = 0.01, p < 0.01, p < 0.01, p < 0.01, and p = 0.01 respectively). Conclusions: Inflammatory markers are unique to gram- positive and gram-negative colonizing pathogens in children with severe burn injury. These predictors may be used for early identification of BWis or may be useful in guiding early, appropriate antibiotic therapy.
Background: Surgical site infection (SSI) rates after colon surgery are being used as a hospital quality measure in the Medicare Hospital Value-Based Purchasing (VBP) program. Reliable reporting and risk adjustment are increasingly debated as VBP assigns greater weight to clinical outcomes. Hypothesis: We expect to identify a discrepancy between two discrete riskadjustment models generated through the Center for Disease Control’s (CDC’s) National Health and Safety Network (NHSN). Methods: We used prospective, clinical data on complex SSIs reported to NHSN from 2012–2014 for a metropolitan health system (6 hospitals, 1,596 procedures). We compared expected quarterly SSIs generated by risk-adjustment models utilized by Centers for Medicare and Medicaid Services (CMS) versus NHSN. The CMS model includes age and ASA classification. The NHSN model includes age, ASA classification, operative length, endoscope or laparoscope, medical school affiliation, hospital bed size, and wound classification. Comparisons were performed using nonparametric statistics. Results: Patients who developed SSIs had the following NHSN risk factors: 92% open procedures, 49% no medical school affiliation, 85% age < 75, 46% ASA > 2, 21% contaminated/dirty wound classification, and 87% OR length ‡ 100 min. Comparison of expected complex SSI rates in colon surgery for all hospitals (1,596 procedures) showed lower rates predicted by CMS vs. NHSN (4.54 vs 4.84, p = 0.003). This difference was again evident when comparing rates within an academic medical center (640 procedures; 1.86 vs. 2.25, p = 0.003) and a community hospital (469 procedures; 1.30 vs. 1.42, p = 0.005). Conclusions: The current risk-adjustment model using only age and ASA classification by CMS predicts consistently lower rates of expected SSI in colon surgery cases throughout a metropolitan health system when compared to expected rates using expanded criteria supported by NHSN. This may lead to lower reimbursement due to limited assessment of risk factors. Further efforts to elucidate appropriate risk adjustment measures without burdening hospitals unnecessarily with expensive data collection are vital to ongoing efforts at quality improvement in US hospitals.
O09. REPAIR OF THE ENTERIC NERVOUS SYSTEM THROUGH VAGALMEDIATED EXPANSION OF NEURAL STEM CELLS Simone Langness, Brian Eliceiri, Raul Coimbra, Todd Costantini, University of California, San Diego Background: The enteric nervous system (ENS) is composed of enteric glia cells and enteric neurons and is a key regulator of epithelial function within the gut as well as an important mediator of the gut response to injury. In order to restore gut barrier function after injury, epithelial cells and cells of the ENS must be repaired or replaced. We have previously shown that the vagus nerve alters the ENS response to injury via direct innervation of the gut. Recently, a population of multipotent progenitor cells called ‘‘enteric neural stem cells’’ (ENSC) have been identified in the intestine that are capable of differentiating into enteric neurons and enteric glia cells. The ability of these ENSCs to respond to intestinal injury and the role of the vagus nerve in mediating their expansion is unknown. Hypothesis: We hypothesized that intestinal ischemia/reperfusion (I/R) injury would result in an expansion of the gut ENSC population and that the ENSC response to injury would be mediated by the vagus nerve. Methods: Mice were subjected to intestinal I/R injury by superior mesenteric artery occlusion (SMAO) for 30 min. In a separate cohort, abdominal vagotomy was performed prior to SMAO. Terminal ileum was harvested at several time points after injury. Gut barrier function was evaluated by measuring in vivo permeability to FITC-Dextran. Quantification of gut ENSCs was accomplished using flow cytometry by measuring the CD49b + lineage population. Results: Intestinal I/R injury caused histologic gut injury at 4 and 24 h post-injury, and was associated with a significant increase in the ENSC population compared to sham at 2, 4, and 8 h after injury. Maximum ENSC increase occurred at 4 h post-injury (2.1% vs. 4.6%, p < 0.001) and returned to baseline by 24 h. Vagotomy prevented the injury-induced increase in the ENSC population seen at 4 h after I/R with ENSC percentage similar to sham. Vagotomy was associated with delayed restoration of gut
O11. RIBSCORE: A NOVEL RADIOGRAPHIC SCORE BASED ON FRACTURE PATTERN THAT PREDICTS PNEUMONIA, RESPIRATORY FAILURE, AND TRACHEOSTOMY Brandon Chapman, Benoit Herbert, Jennifer Salotto, Maridi Rodil, Robert Stovall, Walter Biffl, Jeffrey Johnson, Clay Burlew, Carlton Barnett, Charles Fox, Ernest Moore, Gregory Jurkovich, Frederic Pieracci, University of Colorado, Denver Health Medical Center Background: There is currently no scoring system for rib fractures that relates detailed anatomic variables to patient outcomes. The purpose of this study was to develop and validate a radiographic rib fracture scoring system based on initial CT chest findings. Hypothesis: A radiographic rib fracture score will predict adverse pulmonary outcomes.
ORAL PRESENTATION ABSTRACTS O13. CONTACT ISOLATION IN TRAUMA PATIENTS: AN ANALYSIS OF INFECTIOUS COMPLICATIONS Mark Hamill, Christopher Reed, Sandy Fogel, Eric Bradburn, Kinga Powers, Katie Love, Christopher Baker, Bryan Collier, Virginia Tech Carilion School of Medicine
Methods: We reviewed our trauma registry from Sept 2012-April 2014 for all blunt trauma patients with ‡ 1 rib fracture visualized on CT chest. We identified six candidate radiographic variables and tested their individual associations with pneumonia, defined as clinical suspicion plus quantitative microbiology: 1) ‡ 6 rib fractures, 2) bilateral fractures, 3) flail chest, 4) ‡ 3 severely (bi-cortical) displaced fractures, 5) first rib fracture, and 6) at least one fracture in all three anatomic areas (anterior, lateral, and posterior). Using these variables, we developed the ‘‘RibScore,’’ which ranges from 0–6, and assigns one point for each of the aforementioned variables. The RibScore was then validated among the sample. Our primary outcome measure was pneumonia; secondary outcomes were acute respiratory failure and tracheostomy. Statistics: chi-square, alpha = 0.05. Results: A total of 385 patients with ‡ 1 rib fracture were identified; 274 (71.2%) males, mean age 48.4 y, and mean Injury Severity Score 19.5 points. Of these patients,156 (40.5%) had ‡ 6 rib fractures,120 (31.2%) had bilateral fractures, 46 (11.9%) had flail chest, 32 (8.3%) had ‡ 3 severely displaced fractures, 91 (23.6%) had a first rib fracture, and 58 (15.1%) had fractures in all three anatomic areas. Each of the RibScore component variables was associated individually with pneumonia by univariate analysis (p < 0.05 for each). The median RibScore was 1 (range 0–6). Only 2 patients (0.5%) had a RibScore of 6 and were excluded from analysis. The distribution of the rib score was: Zero (39.2%); one (23.6%); two (16.9%); three (10.1%); four (8.3%); and five (1.3%). RibScore was associated both linearly and significantly with pneumonia (p < 0.01), acute respiratory failure (p < 0.01), and tracheostomy (p < 0.01) (Figure). Conclusions: The RibScore successfully predicted adverse pulmonary outcomes, including pneumonia. The RibScore represents a standardized assessment of fracture severity that may be used for communication and prognostication of the severely injured trauma patient.
Background: Recent studies have demonstrated that contact isolation (CI) may have a significant impact on patient outcomes. We sought to characterize the relationships among CI, victims of trauma, and infectious sequelae at our Level I trauma center. Hypothesis: The use of CI in the trauma population is associated with increases in pneumonia (PNA) and urinary tract infection (UTI) rates. Methods: An existing database of all trauma patients admitted to our Level I trauma center during 2011 and 2012 was queried. Data were collected including demographics, injury severity score (ISS), comorbidities, CI status, and infections. Diagnosis of PNA or UTI was based on clinical documentation in the medical record. A chart review revealed the reason for CI, including specific organisms. Infections were excluded if the CI was the direct result of a new infection. Due to differences in demographics among groups, logistic regression was performed. Results: A total of 4,423 patients were admitted over this period. Of these, 4,317 (97.6%) had complete records and were included in the subsequent analysis. CI was in place in 251 (5.8%) patients; 4,066 (94.2%) were not isolated. 176 (70.1%) had CI initiated for MRSA nasal colonization. 22 (8.8%) had no reason for CI documented. PNA occurred in 193 (4.5%); 58 (23.1%) in the CI group vs. 135 (3.3%) in the non-CI group. UTI was diagnosed in 167 (3.9%); 48 (19.1%) in the CI group vs. 119 (2.9%) in the non-CI group. Using logistic regression, CI, ISS, and gender were significantly associated with PNA and UTI. COPD, alcohol abuse, and obesity were also associated with PNA. Age was significantly associated with UTI. Conclusions: PNA and UTI risks in trauma patients were significantly associated with the use of CI. As the majority of these patients had CI precautions for asymptomatic colonization, the CI provided them no direct benefit. As CI is associated with multiple negative outcomes, its use in the trauma population needs to be carefully reevaluated.
O12. TOP GUNS: THE MAVERICK AND GOOSE OF EMPIRIC THERAPY Stephen Davies, Christopher Guidry, Rhett N. Willis, Zachary Dietch, Puja M. Shah, Robert Sawyer, University of Virginia Health System Background: Vancomycin and piperacillin-tazobactam (P-T) are commonly used first ‘‘guns’’ in the empiric management of critically ill patients. Current studies suggest an increased prevalence of acute kidney injury (AKI) with concomitant use; however, these studies are few and limited by small sample size. The purpose of this study was to compare the prevalence of nephrotoxicity following treatment with vancomycin alone, and concomitant vancomycin and P-T treatment at our institution. Hypothesis: Concomitant vancomycin and P-T treated patients will experience a greater prevalence of nephrotoxicity compared to vancomycin alone-treated patients. Methods: This was a retrospective cohort of patients treated with vancomycin for gram-positive or mixed infections in our facility from 2005–2009, not receiving hemodialysis at time of admission. Included patients were stratified by treatment with vancomycin, vancomycin/P-T, or vancomycin/an alternative gram-negative rod (GNR) antibiotic. P values for categorical variables were computed using chi-square while continuous variables were computed using Kruskal-Wallis. Variables deemed statistically significant (p < 0.0001) were included in the multivariable, log-binomial regression model. Relative risk (RR) and 95% confidence intervals (CI), and p values were computed using a generalized estimating equation (GEE) approach with robust standard errors (i.e., Huber White ‘‘sandwich variance’’ estimates) to accommodate for a correlated data structure corresponding to multiple episodes of infection per individual. Results: A total of 530 patients, with 1,007 episodes of infection, were treated with vancomycin (150), vancomycin/P-T (213), or vancomycin/GNR alternative (167). Patient demographics, comorbidities, sites of infection, and organisms of infection were compared among groups. After adjusting for statistically significant variables, neither vancomycin/P-T (RR = 1.08, 95% CI 0.97-1.2; p = 0.16) nor vancomycin/GNR alternative (RR = 1.08, 95%CI 0.96-1.2; p = 0.21) were found to be associated with an increased risk for nephrotoxicity compared with vancomycin alone. Conclusions: A difference in nephrotoxicity was not observed between vancomycin and vancomycin/P-T-treated patients at our institution. Concomitant use as empiric therapy is appropriate, although larger sample sizes are needed to closely analyze this relationship among ‘‘at-risk’’ subsets of this population.
O14. COMPARING READMISSIONS AND INFECTIOUS COMPLICATIONS OF BLUNT SPLENIC INJURIES USING A STATEWIDE DATABASE Olubode Olufajo, Arturo Rios Diaz, Zara Cooper, Joaquim Havens, Jonathan Gates, Allan Peetz, Ali Salim, Reza Askari, Harvard Medical School, Brigham & Women’s Hospital Background: Conservative management options of blunt splenic injuries (BSI), including the use of splenic artery embolization (SAE) are well described and an acceptable management strategy. However, to date, long-term outcomes of readmission rates and infectious complications comparing different management strategies are lacking. Hypothesis: SAE does not reduce the risk of infectious complications when compared with operative interventions. Methods: Patients ages 18–64 y who sustained BSI were identified in the California State Inpatient Database (2007–11), Healthcare Cost and Utilization Project (HCUP), and categorized into three modes of management: Non-operative (NOM), SAE, and operative management (OM). The cumulative incidence of infections (surgical site infections, pneumonia, urinary tract infections, and sepsis) requiring readmission at different time points after injury were calculated for each mode of treatment and differences were identified using chi-square. Patient and management factors associated with infectious readmissions were determined using multivariable logistic regression models.
ORAL PRESENTATION ABSTRACTS
Results: Among a total of 4,666 BSI patients, 2,830 (60.7%) had NOM, 281 (6%) underwent SAE, and 1,555 (33.3%) had OM. Overall 30-day readmission rate was 8.45%, and 20% were due to infections. Table 1 shows the cumulative incidence of infectious complications during admission, at 30 d and 1 y after injury across all management options. There were no statistically significant differences in the infectious complications between the SAE and OM groups at any given time (Table 2). Multivariable analyses showed Charlson score ‡ 2, length of index admission > 7 d, and both OM and SAE (compared to NOM) were associated with infectious readmissions at 30 d and at 1 y. Conclusions: Although infectious complications are equally common for BSI despite management strategies during the initial admission, infections after SAE and OM are dramatically higher than NOM by 30 d after injury. Interestingly, infectious complications with SAE and OM are equal throughout follow-up.
O15. IMPACT OF TYPE OF INSURANCE ON INFECTION RATES AFTER TRAUMA Jaswin Sawhney, Andrew Stephen, Stephanie Lueckel, Michael Connolly, Charles Adams, Jr., David Tobin Harrington, William Cioffi, Daithi Heffernan, Brown University Background: We have previously shown that insurance, specifically government insurance, affects trauma-related outcomes. Insurance status often affects diagnosis and management of medical conditions. Infection risk is often related to pre-injury management of comorbidities. Despite the Affordable Care Act (ACA) of 2010, with increased government insurance, disparities in access to care and management of baseline health status continue to exist. Hypothesis: Type of insurance will affect infection risk after trauma. Methods: A 10-y retrospective review of blunt trauma patients. Data reviewed included demographics, comorbidities, and injury severity score (ISS). Infections were either clinically evident (e.g., abscess, cellulitis) or culture-based (e.g., UTI, catheter, pneumonia via bronchoalveolar lavage). We divided insurance types into Private/ Commercial (PC), Medicare (MCare), Medicaid (MAid) and Self Pay (SP). Analyses were undertaken for younger (18–45 y) and older ( ‡ 65 y) patients. To assess health care access and maintenance, pre-trauma HbA1c was reviewed in known diabetics. Results: A total of 20,633 patients were included–6,203 PC, 7,636 MCare, 2,798 MAid and 3,996 SP. Among patients aged 18–45 y, SP were youngest (SP = 29.3; PC = 29.8; MAid = 30.3; MCare = 33.9 y; p < 0.05) and had highest ISS (11.4 vs. 10.9 vs. 9.9 vs. 10.5; p < 0.05). Rates of comorbidities were highest in MCare patients (28.1%) vs. PC (16.7%), MAid (19.9%) and SP (12.9%); p < 0.05. Specifically pre-trauma HbA1c was highest in MAid patients (8.8%) vs. PC(7.7%), MCare (7.2%) and SP (7.3%); p < 0.05. Rates of infections were highest in MAid patients (7.7%) vs. PC (5.6%), MCare (6.3%) and SP (4.3%); p < 0.05. Across all insurance groups, the presence of comorbidities was associated with increased risk of infections (OR 4.1; 95%CI 3.2-4.9). Adjusting for age, gender, ISS and number of comorbidities, MAid was associated with a significantly increased risk of infection (OR 1.6; 95%CI 1.1-2.3). This held true across individual specific comparisons, MAid vs. PC (OR 1.9; 95%CI 1.5-2.5), vs. MCare (OR 2.01; 95%CI 1.2-3.2) and vs. SP (OR 2.2; 95%CI 1.7-2.9). Similar finding were noted in the older ( ‡ 65 y) patients. Conclusions: Not all insurance is created equally. Insurance type, specifically MAid, is associated with increased risk of trauma-related infections. Despite the advent of the ACA with potentially more government-insured patients, factors related to reasons for insurance, access, and utilization of health care will continue to exist and affect trauma-related infections.
O16. HYPOTHERMIA PROLONGS THE SURVIVAL OF RATS WITH SEVERE SEPTIC SHOCK BY INHIBITING THE SPLENIC RELEASE OF NEUTROPHILS AND MONOCYTES Rhett N. Willis, Christopher Guidry, Robert Sawyer, Zequan Yang, University of Virginia Health Science Center
Background: Severe sepsis following bacteremia can result in diffuse end-organ damage and increased mortality. The spleen is an important defense organ to fight against bacteremia but could worsen the septic shock by exaggerating inflammatory responses. Hypothesis: We hypothesize that hypothermia therapy will increase overall survival in rats with severe septic shock by inhibiting the splenic release of inflammatory neutrophils and monocytes. Methods: Severe sepsis rat model by cecal ligation and incision (CLI). Hypothermia was induced using cooling blanket to cool the rectal temperature to 31C. 1 h after CLI, rats were assigned to normothermic or hypothermic groups for 4 h with 2 h additional rewarming for hypothermia. Survival was the endpoint. In an additional 2 groups, the spleen was harvested at 1 h after hypo- or normothermic treatment. Results: Survival duration was 2.70 – 0.79 h in normothermic rats (n = 8) and 8.30 – 0.42 h in hypothermic rats (n = 8, p < 0.0001) (Kaplan-Meier). The spleen weight was significantly lower in normothermic rats (0.72 – 0.07 g) than in hypothermic rats (0.81 – 0.10 g, p < 0.05) (Kaplan-Meier). as expressed in Fig. 1. Immunostaining for the expression of formyl peptide receptors (FPR), indicating the presence of neutrophils/ monocytes in the spleen, was considerably higher in hypothermic rats than in the normothermic rats (Fig. 2). Conclusions: Hypothermia therapy significantly prolongs the survival of rats with severe septic shock. Hypothermia dampens the inflammatory response during septic shock by preventing the spleen from releasing activated monocytes/neutrophils into the blood.
O17. LISTERIA MONOCYTOGENES INHIBITS TH17 RESPONSES THROUGH TLR2 SIGNALING Song Liu, Xiuwen Wu, Gefei Wang, Guosheng Gu, Dong Hu, Jianan Ren, Medical School of Nanjing University, China Background: Intestinal pathogens shape mucosal immune responses and determine clinical outcome. Listeria monocytogenes (Lm) can cause severe infection in human
ORAL PRESENTATION ABSTRACTS Hypothesis: Mitochondrial ROS-dependent damage in mtDNA induces cardaic inflammation after sepsis. Methods: Sepsis was induced in SD rats by intratracheal injection of S. pneumoniae (4x106 CFU/rat). Mito-Vit-E (21.5 micromol/kg) or vehicle was administered 30 min post-inoculation and heart tissue was harvested 24 h later for analysis. Results: Sepsis reduced intact mtDNA by 30%, increased mtDNA oxidative modifications, and decreased mitochondria-localized DNA repair enzymes including DNA polymerase gamma, AP endonuclease, 8-oxoguanine glycosylase, and uracil-DNA glycosylase. These changes were not detected in infected animals receiving Mito-Vit-E, indicating mtROS-dependent mtDNA damage in septic hearts. Mito-Vit-E also prevented sepsis-induced defects in mitochondrial respiratory activities and membrane integrity. Furthermore, we detected dramatic increases in cytosolic mtDNA (a type of mitochondrial DAMPs), expression of TLR9 pathway factors MYD88 and RAGE, and interaction between RAGE and one of its ligands TFAM in septic animals. Attenuation of these responses by Mito-Vit-E suggests that mtROS induce inflammation through TLR9. Mito-Vit-E’s anti-inflammatory effect was further demonstrated by decreases in NF-kappa B activation and expression of inflammasome component ASC and cytokine IL-1 beta. Cardiac protection by Mito-Vit-E was shown by reduction in myocardial injury marker troponin-I and amendment of heart morphology after sepsis. Conclusions: Data suggest that mtROS cause mtDNA damage and induce the activation of TLR9-RAGE pathway, at least partially leading to cardiac inflammation and impairment during sepsis. In addition, the data also suggest that mitochondria-targeted antioxidants represent a potential therapeutic approach for sepsis.
O19. BLUE LIGHT REDUCES ORGAN INJURY DURING CRITICAL ILLNESS Du Yuan, Richard Collage, Hai Huang, Xianghong Zhang, Benjamin Kautza, Brian Zuckerbraun, Derek Angus, Allan Tsung, Matthew Rosengart, University of Pittsburgh
beings (listeriosis). Immunologic mechanism of host defenses against Lm has been elusive. Hypothesis: We hypothesize that Th17 responses in listeriosis anticipate Immunological details of how Th17 is regulated by Lm in intestine. Methods: We observed the localization of Lm in small intestine lamina propria and mesenteric lymph nodes using GFP-labeled Lm. We infected IL-17A-GFP mice with Lm for 3 d, and analyzed the Th17 responses in intestine using flow cytometry. We employed TLR2-/- mice, and isolated CD11c + CD103 + dendritic cells (DCs) and CD3 + CD4 + T cells from small intestine lamina propria after Lm infection, then measured Ifnb1 mRNA expression in CD103 + DCs and IL-17A production by CD4 + T cells after co-stimulation by anti-CD3 and anti-CD28 antibodies for 3 d. Results: Lm was detected in the small intestinal lamina propria by confocal microscopy 3 d after infection and thus was able to invade the small intestinal lamina propria (Fig. a, b). We found that during Lm infection, Th17 cells significantly decreased in the lamina propria of small intestine whereas Th17 cell numbers in MLNs remained similar to those found in healthy mice (Fig. c). In support of a direct modulation of mucosal DCs function by Lm, we found that CD103 + DCs expressed significantly higher Ifnb1 mRNA 3 d after Lm infection. Importantly, Lm was unable to prevent the induction of Th17 cells in Tlr2-deficient mice (Fig. d). Conclusions: L. monocytogenes inhibits intestinal Th17 responses dependent on TLR2 signaling. Considering that Lm produces lipoprotein that is predominantly recognized by TLR2 signaling, we assume a potential interaction between lipoprotein and Th17 responses, which has not been fully explored.
O18. MITOCHONDRIAL ROS INDUCES CARDIAC INFLAMMATION VIA DAMAGE IN MITOCHONDRIAL DNA AND STIMULATION OF RAGE PATHWAY IN A PNEUMONIA-RELATED SEPSIS MODEL Qun (Sophia) Zang, Xiao Yao, Deborah Carlson, Steven Wolf, Joseph Minei, University of Texas-Southwestern Medical Center Background: We have previously shown that sepsis impairs cardiac mitochondria, resulting in compromised membrane integrity, an increase in oxidative stress, and a decrease in antioxidant defense using a pneumonia-related sepsis model in rats. Further, when a mitochondria-targeted antioxidant, mitochondria-targeted vitamin E (MitoVit-E), was used in this sepsis model, evidence was collected to support that mtROSmediated mitochondria impairment plays a causative role in myocardial inflammation and cardiac dysfunction during sepsis. Our recent investigation revealed that an important mechanism underling the deteriorative action of mtROS involves damage in mitochondrial DNA (mtDNA) and the activation of TLR9-mtDNA-RAGE pathway in septic hearts.
Background: The current biological evidence suggests that the photoperiodicity of light profoundly influences the physiologic capacity with which an organism responds to stress. However, the ramifications of light intensity and wavelength on the course of critical illness remain to be determined. Hypothesis: We hypothesized that a light of optimal spectrum and illuminance can be identified and broadly applied to modify the biology of critical illness. Methods: Mice (C57BL, 12 wks) were assigned to one of 3 models of septic or sterile insult: 1) 1 cm ligation, 21-g double puncture CLP; 2) segmental hepatic I/R; and 3) unilateral kidney I/R. For 24 h prior to I/R or after CLP, mice were exposed to one of 3 lighting conditions: 1) 1,400 lumens BLUE (peak 442 nm) spectrum; 2) 1,400 lumens, RED (peak 617 nm) spectrum; or 3) AMBIENT white fluorescent light. For CLP, peritoneal lavage fluid and blood were collected to determine bacteria clearance. Acute kidney injury (AKI) was quantified using serum cystatin C concentration. Systemic inflammation was quantified by assaying serum IL-6, IL-10 and TNF-a concentrations. For I/R, liver injury was quantified by assaying serum ALT concentration, and AKI by cystatin C. Serum HMGB1 was measured by immunoblot. Organs were subjected to H & E to quantify the degree of cellular necrosis. Organ myeloperoxidase (MPO) activity was quantified to assess neutrophil concentration. These experiments were repeated using Vsx2or-J/J mice, which undergo optic nerve degeneration. Results: Compared with RED or AMBIENT light, exposure to BLUE light after CLP enhanced peritoneal bacterial clearance (p = 0.07), reduced bacteremia (p < 0.05) and reduced inflammation: IL-6 (p < 0.05), IL-10 (p < 0.05) and TNF-a (p < 0.05). This correlated with reduced AKI and cystatin C (p = 0.06). BLUE light prior to I/R reduced liver and kidney injury: ALT (p < 0.05) and Cystatin C (p < 0.05). In both I/R models BLUE light reduced organ neutrophil influx and MPO (p < 0.05), cellular necrosis (p < 0.05) and the release of HMGB1 (p < 0.05), a key mediator in the pathogenesis of I/R. The protection afforded by BLUE light occurred independent of significant alterations in melatonin or corticosterone concentrations; yet, did involve an optic pathway, as mice experiencing optic nerve degeneration were not protected. Conclusions: These data suggest that high-illuminance BLUE spectrum light can reduce organ injury in critical illness by comparison to RED spectrum or standard low illuminance, ambient, white fluorescent light.
O20. THE COLLAGENOLYTIC ACTIVITY OF FECAL ENTEROC OCCUS FAECALIS PREDICTS ANASTOMOTIC LEAK: DEVELOPMENT OF A NOVEL ASSAY TO CLINICALLY TRACK THE COLLAGENOLYTIC PHENOTYPE Kristina Guyton, Baddr Shakhsheer, Robin Klabbers, James Luo, Monika Krezalek, Lynn Hancock, Olga Zaborina, John Alverdy, University of Chicago Background: Anastomotic leakage is a feared and poorly understood complication of intestinal surgery. We have recently demonstrated that collagenolytic properties of the Enterococcus faecalis gelatinase (GelE) play a key and causative role in anastomotic leak in rats. Hypothesis: Here we hypothesize that the predominance of a collagenolytic phenotype in intestinal E. faecalis predicts anastomotic leak. Methods: Adult rats (n = 17) underwent distal colon resection, local devascularization and recto-sigmoid anastomosis, and were sacrificed six days later and evaluated for evidence of anastomotic leakage (41% leak rate). Pre- and post-operative luminal contents were harvested for analysis. To count individual collagenolytic E. faecalis colonies, we developed a high-throughput method using esculin bile plates complemented with skim milk. Collagenolytic Colony Forming Unit (CCFU) was measured by enumerating enterococcal colonies surrounded by a zone of milk clearing normalized
ORAL PRESENTATION ABSTRACTS
to dry stool weight. Stool CCFU/g was determined at the day of operation (POD0) and the day of sacrifice (POD6) and the difference reflects the in vivo change during anastomotic healing. The novel assay was validated by comparing with the degradation of fluorescent gelatin using wild-type rat intestinal strains, a clinical VRE isolate (V583), and its mutants deficient of, or complemented with, the gelE/sprE operon that expresses quorum-sensing dependent gelatinase activity. Results: Enterococci hydrolyzed esculin producing a black pigment surrounding the colony and many also displayed areas of milk clearing reflecting casein hydrolysis. The area of milk clearing correlated with the level of gelatinase activity in E. faecalis rat intestinal isolates as measured by the fluorescent-labeled gelatin method (n = 24, R2 = 0.80, p < 0.0001). Compared to the lab strain V583, no milk clearing was seen with the gelE deletion mutant. In contrast, over-expression of gelE from a multi-copy plasmid enhanced the zone of clearance. In stool, the lowest change in CCFU/g was observed in rats with minimal leak (Dlog = 0.01) and the highest CCFU/g change was observed in rats with severe leaks (Dlog = 0.92) (p < 0.05). The change in concentration of collagenolytic enterococci in stool correlated with higher clinical leak rate (n = 12, R2 = 0.61, p < 0.005). Conclusions: Microbial collagenolytic activity in stool may be a useful marker to predict anastomotic leak. In addition to E. faecalis, this phenotype association may exist in other intestinal bacteria and is under investigation.
O21. PREOPERATIVE ANTISEPSIS PROTOCOL COMPLIANCE AND THE EFFECT ON BACTERIAL LOAD REDUCTION Peter Lundberg, Alison Smith, Jiselle Heaney, Ronald Nichols, James Korndorffer Jr., Tulane University Medical Center Background: Adequate skin preparation is essential to preventing surgical site infection. Many products are available, each with specific manufacturers’ directions. This lack of standardization may lead to incorrect use of the agents and affect the bacterial load reduction. Hypothesis: A lack of adherence to utilization protocols for surgical skin antiseptics affects bacterial load reduction. Methods: Thirty subjects who routinely perform surgical skin preparation were recruited from 4 hospitals. They completed a questionnaire of both demographics and familiarity with 2 of the most common skin prep formulas: chlorhexidine gluconate/ isopropyl alcohol (CHG/IPA) and povidone-iodine (PVI) scrub and paint. Randomly selecting one formula, subjects performed skin preparation for ankle surgery on a healthy standardized patient. This was repeated using the second formula on the opposite ankle. Performance was recorded and reviewed by two independent evaluators using standardized dichotomous checklists created against the manufacturer’s recommended application. Swabs of the patients’ first interweb space and medial malleolus were obtained before, 1 min after, and 30 min after prep and plated on Luria Bertani agar. Bacterial loads were measured in colony forming units (CFUs) for each anatomical site. Data were analyzed using ANOVA and a univariate linear regression. Results: Subjects had an average of 12.7 – 2.2 years operating room experience and 8.8 – 1.5 years of skin prep experience. Despite this, nobody performed 100% of the manufacturers’ steps correctly. All essential formula-specific steps were performed 90% of the time for CHG/IPA and 33.3% for PVI (p = 0.0001). No correlation was found between experience or familiarity and number of correct steps for either formula. Average reduction in CFUs was not different between CGH/IPA and PVI at 30 min for all anatomical sites (75.2 – 5.4% vs. 73.7 – 4.5% p = 0.7662). Bacterial reductions at 30 min following skin prep were not significantly correlated with operator experience, protocol compliance, or total prep time for either formula. Conclusions: This study demonstrates problems with infection prevention as those tasked with preoperative skin preparation do so with tremendous incongruence according to manufacturer guidelines. No effect on bacterial load was identified, however with a larger sample size this may be noted. Standardization of the prep solutions as well as simplification and education of the correct techniques may enhance protocol compliance.
O22. NECROTIZING ENTEROCOLITIS: DOES PERFORATION MATTER? Varun Bhalla, Gezzer Ortega, Gillian Abrams, Margaret McGuire, Seth Goldstein, Vanessa Pinard, Mariam Said, Faisal Qureshi, Children’s National Medical Center Background: Necrotizing enterocolitis (NEC) continues to cause significant mortality and morbidity in neonates despite evolving surgical management over the last decade. The aim of our study was to evaluate the early ( < 30 d) outcomes of management strategies at a single referral institution. Hypothesis: We hypothesized that premature newborns with intestinal perforation had a higher mortality rate than those without perforation. Methods: We performed a 3-y retrospective review (2011–2014). Inclusion criteria were neonates diagnosed with NEC > stage I or perforation. Patients were grouped by peritoneal drainage (PD), exploratory laparotomy (EXLAP), and non-operative (NOP) management. Demographic data, birth weight, age, and age at perforation were extracted. The primary outcome was mortality. Results: 163 patients were evaluated (58.9% male) with an average age at admission of 16.9 d, birth weight of 1139.9 g, and gestational age of 27.8 wk. 53.4%(n = 87) presented with perforation. These were smaller, more premature, and presented earlier than non-perforated (p < 0.02). 54% (n = 47) underwent PD, 40% (n = 35) EXLAP, and 6%(n = 5) had no intervention. Of the non-perforated patients (n = 76, 46.6%), 75%
(n = 57) required no surgical intervention and 25% (n = 19) had an ex-lap. Overall early mortality was 20.2% (n = 33) with 27.6% (n = 24) in the perforated group and 12% (n = 9) in those non-perforated (p = 0.001). Patient characteristics and outcomes based on management are seen in Table 1. Neonates without perforation but requiring laparotomy had the highest mortality rate (p = 0.002). On adjusted analysis, neonates with perforation had a higher likelihood of death (OR 2.81, 95%CI 1.16-6.84). Conclusions: Smaller and more premature neonates presented with perforation and had a higher mortality. Exploratory laparotomy was preferred in the older, larger newborns that presented later with perforation but had no difference in mortality. Neonates without perforation failing medical management presented late and may be reflective of delayed referral.
O23. ABDOMINAL COMPARTMENT SYNDROME, CEREBRAL INFARCTION, AND ACUTE RESPIRATORY DISTRESS SYNDROME ARE THE BIGGEST MODIFIABLE RISK FACTORS FOR SURGICAL SITE INFECTIONS IN BLUNT TRAUMATIC HEMORRHAGIC SHOCK John Hwabejire, Christine Nembhard, Tolulope Oyetunji, Theodros Seyoum, Olumayoma Pitan, Suryanarayana Siram, Edward Cornwell III, Wendy Greene, Howard University Hospital Background: Infections are key contributors to the trimodal distribution of traumatic deaths. However, the factors that increase surgical site infection (SSI) risks after operative interventions in traumatic hemorrhagic shock (HS) are incompletely defined. We identified variables that increase SSI risks in blunt traumatic HS. Hypothesis: Modifiable factors after HS are associated with increased SSI risks. Methods: The ‘‘glue grant’’ database was analyzed. Patients age ‡ 16 y who had surgery and survived were included. Those who developed an SSI (SSIs) were compared with those who did not (No-SSIs). Univariate and multivariable analyses were used to determine predictors of developing an SSI. Results: 1,552 patients were included, of whom 240 (15.5%) had an SSI. There was no difference in age, gender, race, pre-injury comorbidities or Injury Severity Score between SSIs and No-SSIs. Compared to No-SSIs, SSIs had a higher initial heart rate (114 – 27 vs. 110 – 26, p = 0.012), lactate (4.7 – 2.5 vs. 4.1 – 2.4, p = 0.001), INR (1.5 – 0.7 vs. 1.4 – 0.4, p < 0.001), multiple organ failure score (6.1 – 2.5 vs. 4.8 – 2.2, p < 0.001), volume of transfused blood (3,252 – 3,086 mL vs. 2,152 – 2,250, p < 0.001), volume of crystalloids (12,994 – 7,290 mL vs.10,210 – 5,202, p < 0.001), hospital length of stay (d) (41 – 36 vs. 24 – 20, p < 0.001), ICU days (21 – 17 vs. 13 – 11, p < 0.001), and ICU ventilation days (16 – 15 vs. 9 – 10, p < 0.001). SSIs also had a higher incidence of abdominal compartment syndrome, ACS (13.8% vs. 3.3%, p < 0.001), acute respiratory distress syndrome (ARDS) (38.3% vs. 19.9%, p < 0.001), cerebral infarction (5.4% vs. 1.6%, p = 0.001), extremity compartment syndrome (5.4% vs. 2.8%, p = 0.038), and rhabdomyolysis (7.5% vs. 2.1%, p < 0.001). Laparotomy (Pearson R = 0.081, p = 0.001), soft tissue debridement (Pearson R = 0.197, p < 0.001) and thoracotomy (Pearson R = 0.097, p < 0.001) correlated positively with SSI. Independent predictors of having an SSI include cerebral infarction (OR, 2.92; 95%CI 1.31-6.50, p = 0.009), ACS (OR 2.37, 95%CI 1.33-4.23, p = 0.004), ARDS (OR 1.63, 95%CI:1.12-2.39, p = 0.012), laparotomy (OR 1.47, 95%CI 1.04-2.08, p = 0.031), soft tissue debridement (OR 2.87, 95%CI:2.034.05, p < 0.001), and thoracotomy (OR1.94, 95% CI:1.18-3.21, p = 0.009). The rate of SSI was 43.4% in patients with ACS, 38.2% in those with cerebral infarction and 26.1% in those with ARDS. Conclusions: ACS, ARDS, and cerebral infarction are the major modifiable risk factors for the development of SSIs after life-saving surgical interventions for blunt traumatic HS, and represent targets for reduction of SSI-associated morbidity and mortality.
S-16 O24. DO POLYMICROBIAL INTRA-ABDOMINAL INFECTIONS HAVE WORSE OUTCOMES THAN MONOMICROBIAL INTRA-ABDOMINAL INFECTIONS? Puja M. Shah, Brandy Edwards, Zachary Dietch, Robert Sawyer, University of Virginia Health Science Center Background: Numerous studies have demonstrated microorganism interaction through signaling molecules, some of which are recognized by other bacterial species. This interspecies synergy can ultimately be detrimental to the human host in polymicrobial infections. Hypothesis: We hypothesize polymicrobial intra-abdominal infections (IAI) have worse outcomes than monomicrobial infections. Methods: Data from STOP-IT, a prospective, multicenter, randomized controlled trial was reviewed for all occurrences of IAI with culture results available. Patients in STOP-IT were randomized to receive four days of antibiotics versus antibiotics until clinical symptom resolution plus an additional 2 d. Patients with polymicrobial and monomicrobial infections were compared by univariate analysis using Wilcoxon rank sum, Chi-square, and Fisher exact tests. Results: Culture results were available for 328 of 518 (63%) patients in the original study. Overall, duration of antibiotic therapy between polymicrobial (n = 219) and monomicrobial IAI (n = 109) were equal (p = 0.97). Univariate analysis demonstrated similar demographics between the two populations. 35 patients with inflammatory bowel disease (11%), had a higher association with polymicrobial IAI (p = 0.03). Polymicrobial infections were not associated with higher risk of surgical site infection, recurrent IAI, or death (Table 1). Conclusions: Contrary to our hypothesis, polymicrobial IAI are not associated with worse outcomes when compared to monomicrobial infections. These results suggest polymicrobial IAI can be treated similarly to monomicrobial IAI.
O25. THE INFLUENCE OF BETA-LACTAM PRESCRIBING PATTERNS ON RESISTANCE RATES AMONG VARIOUS ADULT ICU POPULATIONS
ORAL PRESENTATION ABSTRACTS Methods: We collected drug consumption data of meropenem use across three ICU populations including trauma/surgical, cardiovascular, and medicine ICUs in 2013. Antibiotic usage was classified using the World Health Organization definition of defined daily dose (DDD). These DDD were further categorized by ICU per 1,000 patient/ days (pt/d). The susceptibility rates of piperacillin-tazobactam to Pseudomonas aeruginosa was also collected for each unit. Results: The total DDD by ICU per 1,000 pt/d was 21.97, 101.62, and 157.35 for trauma/surgical, cardiovascular, and medicine ICUs respectively, in 2013. Susceptibility rates of piperacillin-tazobactam to P. aeruginosa were 94%, 67%, and 64% for trauma/ surgical, cardiovascular, and medicine ICUs, respectively. Pearson correlation coefficient was r = - 0.97, p = 0.157. Conclusions: Meropenem usage is inversely correlated to piperacillin-tazobactam susceptibility to P. aeruginosa. Further analysis should be done to investigate other correlations of increased antibiotic use to gram-negative bacterial resistance. When possible, meropenem should be reserved for known or suspected multi-drug-resistant bacterial infection.
O26. PROPHYLACTIC GENTAMICIN IS NOT ASSOCIATED WITH ACUTE KIDNEY INJURY IN PATIENTS WITH OPEN FRACTURES Jeffrey Tessier, Billy Moore, Therese Duane, JPS Health Network, Fort Worth Background: Data on antimicrobial prophylaxis for open fractures are limited, with many protocols based on expert opinion from 50 y ago. These protocols include aminoglycosides (AGs), particularly for fractures associated with significant soft tissue injury, and these drugs are associated with an increased risk of acute kidney injury (AKI) in other settings; this risk has not been defined for open-fracture prophylaxis. Hypothesis: The purpose of this trial was to evaluate the risk of AKI with the use of AGs for prophylaxis of open fractures. Methods: We performed a retrospective study of trauma registry data from May 2012 to October 2014 at our Level 1 trauma center. Patients with open fractures were evaluated for demographics, location/type of fracture, injury severity, and receipt of an AG. Patients with and without AG prophylaxis were compared for rates of AKI, infection, and outcomes. Groups were compared statistically using Student t-test; and logistic regression was used to calculate odds ratios for risk factors associated with AKI. Results: There were 167 patients with open fractures during the study period (119 males, mean age 42 – 17 y), with 80 (48%) receiving an AG (gentamicin) for prophylaxis (AG + group). AG + and AG - patients had similar sites of fracture and injury severity scores (ISS,12.6 – 9.9 AG + ; 15.9 – 13.2 AG - , p = 0.07), but were more likely to have blunt trauma (96% AG + ; 77% AG - , p < 0.001) or receive iv contrast £ 48 h from admission (75% AG + ; 56% AG - , p = 0.01). In a multivariable logistic regression model, receipt of gentamicin was not associated with AKI (OR 0.2, 0.02-2.44, p = 0.22), whereas hypotension on admission (OR 10.7, 1.42-80.93, p = 0.02) and ISS (OR 1.1, 1.01-1.20, p = 0.02) were both associated with AKI during the incident admission. All patients with AKI had received iv contrast £ 48 h from admission. Only 4 fracture site infections were identified, all in the AG - group. Overall mortality was higher in the AG - group (3.8% AG + , 12.6% AG - , p = 0.04). Conclusions: Gentamicin is not associated with AKI when used for prophylaxis of open fractures. Not surprisingly, hypotension on admission and higher ISS were associated with an increased risk of AKI in patients with open fractures. Only 4 fracture site infections were identified in this study, all in patients who did not receive AGs. Gentamicin was not associated with an increased risk for AKI in this study, but the use of nephrotoxic agents should be limited in open fracture patients presenting with hypotension or high injury severity.
Sara Parli, Wilbur Rutter, Daniel Davenport, Phillip Chang, University of Kentucky Background: Current knowledge exists that overuse of antibiotics leads to increased bacterial resistance to drug therapy. Gram-negative bacterial resistance is increasing in prevalence, with clinicians at heightened concern, especially in the intensive care unit (ICU). Meropenem has been described in the management of intra-abdominal infection, specifically in moderate-to-severe infection. Meropenem has also been reported to induce chromosomal beta-lactamases, specifically in vitro. Limited data is published regarding this resistance pattern and meropenem usage in the adult ICU patient population. Hypothesis: Increased use of meropenem leads to increased resistance of other betalactams to gram-negative bacteria.
O27. PAUCITY OF BACTERIA IMPLICATED IN PATHOGENESIS OF EXPERIMENTAL NECROTIZING ENTEROCOLITIS Joanna Lim, Gene Jang, Brandon Bell, Jamie Golden, Jordan Bowling, Jin Wang, Larry Wang, Anatoly Grishin, Henri Ford, University of Southern California, Children’s Hospital of Los Angeles Background: Although the etiology of necrotizing enterocolitis (NEC) is not clear, abnormal bacterial colonization of the gastrointestinal tract may play a critical role in its pathogenesis. Consistent with this theory, prompt administration of broad spectrum antibiotics remains a cornerstone of clinical management of NEC. However, administration of antibiotics to vulnerable infants could predispose to the development of NEC by altering the intestinal microbial flora. Hypothesis: We hypothesize that antibiotic administration predisposes to the development of NEC by altering the intestinal microbiota. Methods: We induced NEC in neonatal rats by subjecting them to formula feeding and hypoxia thrice daily. There were six treatment groups: Formula feeding/hypoxia alone; or with early (starting day of life #1); or late (starting day of life #3) ampicillin administration; addition of the opportunistic pathogen Cronobacter muytjensii alone; or in combination with early or late ampicillin administration. Animals were sacrificed on day of life #4. The terminal ileum was scored histologically (NEC ‡ 2). Microbiota was characterized by culture-based 16S rRNA sequencing. Results: Formula feeding and hypoxia alone caused a NEC incidence of 29%. As expected, C. muytjensii increased the incidence of NEC to 69% (p = 0.0013 compared to baseline). However, the total bacterial load in this group was low, 102-105/mL specimen. When ampicillin was given early with C. muytjensii, the incidence of NEC decreased to 25% (p = 0.0185 compared to C. muytjensii alone) but the total bacterial load was higher, ranging 107-109/mL. Late administration of ampicillin with C. muytjensii resulted in an incidence of 71% (p = 0.0047 compared to baseline) and a low total bacterial load of less
ORAL PRESENTATION ABSTRACTS
than 102/mL. Ampicillin alone, regardless of timing, produced a high incidence of NEC (early 67%, late 75%) and low bacterial load of less than 102/mL. Conclusions: C. muytjensii not only exacerbates NEC but decreases colonization of other bacterial species, possibly by competition. Ampicillin is beneficial when administered early together with a susceptible opportunistic pathogen. This beneficial effect is associated with increased colonization by other bacteria. Thus, early, targeted antibiotic administration against an opportunistic pathogen may limit its growth while allowing subsequent colonization of commensal bacteria. However, antibiotic administration in the absence of a putative pathogen could be detrimental and lead to the development of NEC.
O28. PRE-B CELL COLONY ENHANCING FACTOR (PBEF)/NAMPT PHOSPHORYLATION BY PI3 KINASE IS INDISPENSABLE FOR THE INHIBITION OF NEUTROPHIL (PMN) APOPTOSIS IN PATIENTS WITH SEPSIS Song Jia, Jean Parodo, John Marshall, University of Toronto, St. Michael’s Hospital Background: We have reported that delayed apoptosis of PMN from patients with sepsis requires expression of PBEF/Nampt, the rate-limiting enzyme in a salvage pathway of NAD biosynthesis, and the activity of PI3 kinase (PI3K). Hypothesis: We hypothesize that PBEF/Nampt activity is dependent on PI3-kinasemediated serine phosphorylation. Methods: We studied PMN from healthy controls or ICU patients with severe sepsis (n = 9), and HEK293 cells stably transfected with WT or mutant PBEF-myc. Apoptosis was quantified by flow cytometry as the uptake of propidium iodide, and NAD was measured by thiazylol blue assay. Phosphodeficient PBEF was created by mutation of Ser199 to Ala (A), and phosphomimetic PBEF by Ser199 mutation to Glu (D). PI3K activity was inhibited by Ly294002 (20 mM), and PBEF/Nampt activity by APO866 (10 nM). Results: Compared with controls, septic PMN apoptosis was delayed (4.7 – 3.5 vs .50.0 – 8.6%, p < 0.001), and intracellular NAD increased (17.2 – 6.2 vs. 4.5 – 2.2 pMol, p < 0.001). Both Ly294002 (25.2 – 8.0%, p < 0.01) and APO866 (20.1 – 5.6%, p < 0.01) increased septic MPN appoptosis and reduced NAD levels (Ly 4.4 – 3.8, APO 5.3 – 3.8 pMol, p < 0.01). Intracellular NAD was increased in HEK293 cells transfected with rPBEF or S199D phosphomimetic PBEF (5.4 – 1.3 pMol to 16.2 – 2.4 and 16.2 – 2.9 pMol; p < 0.01). Phosphodeficient S199A PBEF had no effect on NAD levels, but increased spontaneous apoptosis from 1.4 – 1.1% in controls to 11.3 – 2.3% (p < 0.01). Western blots of septic PMN (n = 4) revealed increased expression of the active p110 subunit of PI3K; Ly294002 induced time-dependent serine dephosphorylation of PBEF (Figure). Coimmunoprecipitation studies showed that PBEF bound the PI3K p110 subunit, but not the p85 regulatory subunit in septic PMN; this interaction was blocked by Ly294002. PBEF dimerized in HEK293 cells transfected with myc- and GFP-tagged WT or S199D, but not S199A PBEF; Ly294002 prevented the dimerization of WT PBEF. Conclusions: PI3 kinase serine phosphorylates PBEF, promoting its dimerization and Nampt activity, and supporting prolonged PMN survival in septic patients. Inhibition of this process restores the normal kinetics of PMN apoptosis, and potentially supports the resolution of PMN-mediated inflammation in sepsis.
O29. ACUTE APPENDICITIS IN CHILDREN IS ASSOCIATED WITH AN ABUNDANCE OF BACTERIA FROM THE GENUS FUSOBACTERIUM Matthew Rogers, Rachel Brower-Sinning, Brian Firek, Min Shi, Diana Zhong, Michael Morowitz, University of Pittaburgh, Children’s Hospital of Pittsburgh Background: Although luminal obstruction has typically been viewed as the cause of appendicitis, recent evidence suggests that the disease results from invasion by specific pathogens. Recently, we reported an abundance of bacteria from the genus Fusobacterium in appendices of patients with acute appendicitis (AA). Here we expand our sample size to validate these preliminary findings. Hypothesis: We hypothesize that appendices of children with AA are enriched with Fusobacterium relative to children without appendicitis. Methods: Appendix swabs were collected from children < 18 y undergoing ileocecectomy for IBD (n = 7), incidental appendectomy for reasons other than appendicitis (n = 11), or appendectomy for AA (n = 59). Appendicitis specimens were characterized as simple (n = 39), perforated (n = 12), or interval (n = 8). After isolation of bacterial DNA, 16S ribosomal RNA gene sequences were sequenced on the Roche 454 or Illumina Miseq platforms. Computational analysis of the sequencing reads was performed with UPARSE and QIIME. Results: Species richness was similar, but taxonomic composition was markedly different between AA and non-appendicitis samples. As shown, swabs from AA patients
harbored an increased abundance of members of the genus Fusobacterium relative to incidental and ileocecectomy samples (Wilcoxon rank-sum test. p = 0.002). Conversely, Bacteroides was markedly depleted in appendicitis groups (p = 0.015). We also identified several low-abundance taxa (e.g., Campylobacter) that were present mainly in AA samples. Subgroup analysis of appendicitis specimens suggests an enrichment of Clostridiales in perforated AA specimens, suggesting a shift towards anaerobic metabolism in the progression from simple to perforated appendicitis. Conclusions: Our results strongly support an association between AA and alterations in the appendiceal microbiome, specifically an increase in Fusobacterium and a decrease in Bacteroides. Follow-up studies are required to determine how this knowledge can be leveraged to improve the diagnosis or treatment of patients with acute appendicitis.
O30. EFFECT OF REMOTE ISCHEMIC PRECONDITIONING ON LPS-INDUCED PULMONARY INFLAMMATION IN MICE So Jung Choi, Ori Rotstein, University of Toronto, St. Michael’s Hospital Background: Remote ischemic preconditioning (RIPC) is an intervention that involves application of multiple cycles of ischemia/reperfusion to an extremity. It prevents pulmonary inflammation when applied prior to hemorrhagic shock and resuscitation. The protective effect of RIPC in part comes from the release of a humoral factor(s) that reduces neutrophil migration to the site of injury. As an effective intervention, RIPC may not be limited to ischemia/reperfusion injury, but also exert its protective effects on other inflammatory diseases such as acute lung injury (ALI). Hypothesis: RIPC treatment is expected to have a protective effect against lipopolysaccharide (LPS)-induced pulmonary inflammation and injury. Methods: Male C57BL/6 mice (9–12-wk-old) were anesthetized via intraperitoneal injection of sodium pentobarbital (70 mg/kg) and subjected to RIPC or sham treatment. RIPC involved 4 cycles of 5-min ischemia and 5-min reperfusion being applied to the right hind limb using a tourniquet. Following the intervention or sham treatment, 50 mcL of LPS (800 mcg/kg) or phosphate-buffered saline was administered intratracheally. Mice were sacrificed and bronchoalveolar lavage (BAL) was performed at 4 h post-injection. BAL fluid (BALF) was assessed for quantification of immune cell populations and protein content. Results: Intratracheal LPS administration caused massive neutrophil infiltration into the alveolar space by 4 h. BALF neutrophil count was significantly reduced in mice that were conditioned prior to LPS administration (R-LPS = 1.52*105 cells/mL, n = 8) compared to that of LPS-only mice (LPS = 3.79*105 cells/mL, n = 8, p < 0.05). It was decreased by 25% in the RIPC-LPS group relative to LPS-only group (R-LPS = 49%, LPS = 74%, n = 8, p < 0.05). Total leukocyte counts did not differ significantly between groups (sham = 4.13*105, LPS = 4.90*105, R-LPS = 2.83*105, n = 4-8, p > 0.05). LPS treatment caused a modest increase in BALF protein content in both groups at 4 h. Although it did not differ significantly between RIPC-LPS (R-LPS = 0.095 mcg/mcL, n = 8) and LPS-only (LPS = 0.124 mcg/mcL, n = 8, p = 0.48) groups, the results exhibited a trend consistent with the hypothesis. Conclusions: RIPC significantly reduced pulmonary inflammation following challenge with LPS at 4 h post-injection. Its protective effect may allow application of RIPC as an intervention for the treatment and prevention of ALI as well as other conditions involving inflammation.
O31. LATENT CYTOMEGALOVIRUS INFECTION PREDISPOSES IMMUNE COMPETENT HOSTS TO PRO-INFLAMMATORY PULMONARY IMMUNE RESPONSES Varun Dwivedi, Joanne Trgovcich, Sara Mansfield, Sara Byrd, Charles Cook, Harvard University
S-18 Background: Cytomegalovirus (CMV) is a ubiquitous virus infecting most human beings and developing persistent latent infections. CMV is an accepted life-threating pathogen in immune suppressed patients that is increasingly being recognized as a potential pathogen in critically ill immune-competent patients. We have observed the occurrence of CMV reactivation in the lungs of *33% of immune-competent patients during critical illness, associated with roughly doubled durations of mechanical ventilation. Hypothesis: We previously have shown that bacterial sepsis can cause CMV reactivation in immuno-competent hosts. We hypothesized that latent CMV infection alters the cellular composition and immune function of cells in the lungs in a manner that worsens lung injury during sepsis. Methods: BALB/c mice were infected with 1 · 106 PFU of Smith strain murine CMV and isolated lung mononuclear cells (LMNC) were characterized by flow cytometry, and also stimulated in vitro with LPS to model their in vivo septic response. In a separate experiment, naı¨ ve and latent CMV mice underwent cecal ligation and puncture (CLP) to induce sepsis in vivo. Mice were evaluated by flow cytometry at 24, 48 and 72 h post-CLP for immune cell composition. Results: We found that unstimulated LMNC from CMV latent mice excrete more TNF-a and IL-6 than naı¨ ve mice, and latent LMNC also respond more vigorously to LPS and Con-A than naı¨ ve LMNC. This was associated with significant increases in the LMNC frequency of CD4 + , CD8 + T cells and Gr1 + cells compared to naı¨ ve mice. Cells resembling myeloid-derived suppressor cells (MDSC, Gr1 + CD11b + ) were unchanged during acute infection, but were significantly increased during latency. Intracellular flow cytometry showed that Gr1 + cells were major TNF-a producers. Further, using our murine sepsis model we found that CMV-latent mice had higher cellular accumulation of CD14 + and CD11b + cells in lungs compared to naı¨ ve mice at 24 h post-CLP. However, at later time points 48, 72 h post-CLP, both naı¨ ve and latent mice showed similar lung cellular infiltration. Conclusions: Our findings suggest that CMV infection dramatically alters the lung immune environment. During latency there is a persistent pro-inflammatory lung immune environment as evident by elevated TNF-a and IL-6 levels. In-vitro this TNF-a responsiveness is associated with GR1 + cells. In-vivo, CMV latent mice show an early, more aggressive recruitment of CD14 + and CD11b + cells during bacterial sepsis that may contribute to immune-mediated pathology.
O32. DEFINING THE MITOCHONDRIAL DAMP REPERTOIRE: FORMYL PEPTIDES ARE NOT ALL CREATED EQUAL! Elzbieta Kaczmarek, Michael Marusich, Nicola Sandler, Yan Campbell, Christopher Barrett, Michael Yaffe, Leo Otterbein, Kiyoshi Itagaki, Carl Hauser, Harvard Medical School, Beth Israel Deaconess Medical Center Background: Mitochondria-derived damage-associated molecular patterns (mtDAMPs) are released from injured tissues by trauma and activate innate immunity. Mitochondrial DNA codes for 13 n-formyl peptides (mtFP) that are presumed to be neutrophil (PMN) chemoattractants and activators like canonical bacterial FPs (e.g., fMLP). If, like fMLP, wound mtFPs create chemoattractant local gradients and suppress PMN expression of other chemotactic receptors, they may be critical modulators of systemic bacterial clearance after trauma. Hypothesis: Individual mtFPs may have important functional differences that that will inform their value as biomarkers or therapeutic targets. Methods: The n-terminal peptides of all 13 mtFP were synthesized as were homologous non-formylated mt-peptides. The activity of each peptide was assayed as intracellular calcium flux ([Ca2 + ]i) in FURA-2AM labeled human PMN and as PMN chemotaxis (CTX) in transwells. Crosstalk with other chemoattractant receptors (BLT1, CXCR2) was assayed as heterologous suppression of responses to LTB4 and GROa. Results: Five mtFP induced concentration-dependent [Ca2 + ]i flux and CTX in native PMN; eight did not. Only mtFPs that induce [Ca2 + ]i flux induce CTX. Nonformylated mtFP neither induce [Ca2 + ]i flux/CTX, nor block PMN response to active mtFPs. Cyclosporine H (an inhibitor of FP receptor-1) blocks responses to all mtFP.
ORAL PRESENTATION ABSTRACTS Exposure to any active mtFP desensitizes PMN [Ca2 + ]i flux and CTX response to LTB4, GROa and fMLP. Mice were inoculated with active mtFPs and monoclonal antibodies were generated: mAbs thus created recognize the mtFP sequence alone, in Western blots using the parent protein, and blocked [Ca2 + ]i responses only to that specific mtFP. Conclusions: Only five of the 13 mtFP are involved in activation of PMN by tissue injury. These DAMP motifs can act locally as PMN chemoattractants toward dead and dying tissues but they may simultaneously desensitize PMN chemotactic receptors that are needed for systemic innate immune functions. To the extent that this renders the host susceptible to infection, active mtFPs may therefore prove good biomarkers for the severity of trauma and infection risk. The active mtFPs may be key targets for diagnostic and therapeutic agents.
O33. DOES CIRCADIAN RHYTHM AFFECT THE RISK FOR POSTOPERATIVE INFECTIOUS COMPLICATIONS? Christopher Guidry, Stephen Davies, Rhett N. Willis, Zachary Dietch, Puja M. Shah, Robert Sawyer, University of Virginia Health Sciences Center Background: Surgical care is delivered 24 h/d, 7 d/wk at most institutions. Alarmingly, some authors have found that operative start times may be associated with increased morbidity and mortality. This effect has been noted in both the public and private sector. Although some of these differences may be related to process, they may also be related to the human circadian rhythm and changes in host defense. Hypothesis: We hypothesized that the time of day would significantly impact the frequency of post-operative infectious complications. Methods: Cases at a single tertiary-care center reported to NSQIP over a 10-y period were identified. Operative start times were divided into 6-h blocks with the time period from 6 AM to Noon serving as the reference. Standard univariate techniques were used. Multivariable logistic regression with mixed effects modeling was used to determine the relationship between operative start times and infectious outcomes controlling for surgeon clustering. For the purposes of this analysis, significance was set at p < 0.01. Results: A total of 21,985 cases were identified. 2,764 (12.6%) were emergent. Overall 9.7% (n = 2,142) experienced some form of infectious or post-operative complication. Seventy percent of these infections (n = 1,506) were surgical site infections. By univariate analysis considering all cases, nighttime and evening operations had higher rates of post-operative infections compared to those in occurring during the day (9.1% from 6 AM to Noon; 9.7% from Noon to 6 PM; 14.8% from 6 PM to Midnight; and 14.4% from Midnight to 6 AM; p < 0.001). By multivariable analysis, operative start time was not associated with risk of post-operative infection even when emergent cases were considered independently (Table). Conclusions: Our data suggest operative start times have no correlation with postoperative infectious complications. Further work is required to identify the source of the time-dependent outcome variability observed in previous studies.
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O35. OBESITY PARADOX IN PATIENTS WITH SOFT TISSUE INFECTIONS NATIONWIDE Elissa Lin, Katherine Williams, Wei Jiang, Vihas Patel, Naomi Shimizu, Zara Cooper, Joaquim Havens, Ali Salim, Reza Askari, Harvard University, Brigham & Women’s Hospital Background: While the obesity paradox has been described in patients with certain chronic diseases, there are no studies that examine the effects of obesity among surgical patients with soft tissue infections (STI). Recently work by our group has shown a trend towards lower mortality in obese patients with necrotizing soft tissue infections. The purpose of this study was to study the relationships among obesity, types of nutritional support, and outcomes in patients with STI. Hypothesis: The obesity paradox is exhibited in patients with STI, despite the type of nutritional support received. Methods: The Nationwide Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality (AHRQ) database was used to review patients retrospectively with STI from 2006 to 2010. Patients with NIS Clinical Classification Codes for debridement of wound; infection, or burn were included. Subjects were categorized by type of nutritional support received: Artificial nutrition through tube feeds (enteral) or total parenteral nutrition (TPN), or nonartificial. We compared in-hospital mortality of non-obese vs. obese patients. A multivariable analysis using chi-square was conducted to identify predictors of mortality. Results: Of 31,325 patients with STI, 94.1% received non-artificial nutrition, 3.2% of patients received TPN, and 2.7% received tube feeds. All differences in mortality rates between obese vs. non-obese were statistically significant regardless of feeding practice (Table 1), and obese patients fared better than nonobese patients (p < 0.001). Type of nutritional support and non-obesity were found to be significant predictors of mortality after controlling for all other factors. Regardless of the type of nutrition support, the odds of obese STI patients dying in the hospital were half (Odds Ratio 0.52, 95%CI 0.352-0.782) that of non-obese patients. Conclusions: Despite type of nutritional support, obesity is significantly protective of in-hospital mortality in patients with STI, suggesting that the obesity paradox exists in this patient population. Further work is required to validate the obesity paradox in this population.
O36. DEVELOPING A SSI RISK SCORE INCORPORATING DAILY OBJECTIVE WOUND ASSESSMENTS USING MACHINE LEARNING Patrick Sanger, Gabrielle van Ramshorst, Ezgi Mercan, Meliha Yetisgen, Andrea Hartzler, Cheryl Armstrong, Ross Lordon, Sarah Han, William Lober, Heather Evans, University of Washington Background: Surgical site infection (SSI) remains a common, costly, and morbid healthcare-associated infection. Prediction of SSI may facilitate earlier recognition and treatment, yet previous SSI risk scoring systems only consider baseline risk factors (BF) on the day of operation, not accounting for changing risk over time after surgery. Hypothesis: Incorporation of daily wound assessment improves the accuracy and timeliness of SSI prediction compared to traditional BF alone. Methods: A prospective cohort of 1,000 patients scheduled for open abdominal surgery at an academic teaching hospital were examined daily until discharge. Patients who didn’t undergo surgery (n = 33) or with < 2 d of wound observations (n = 107) were excluded. We collected patient and procedure BF and compared SSI vs. non-SSI groups using univariate methods. Daily observations of wound features (e.g., exudate) were recorded. Our primary outcome was CDC-defined SSI. Using supervised machine learning, we trained 3 naı¨ ve Bayes classifiers incorporating correlation-based feature subset selection, evaluated using 10-fold cross validation: 1 with BF, 1 with repeated features (RF) and 1 with both. To train the classifiers, patient data from 1–3 d prior to SSI were used to predict diagnosis on day 0. For patients without in-hospital SSI, we matched 3 similar consecutive post-op days. Accuracy, predictive values, and AUC were calculated. Results: Of 860 patients included in analysis, 20.3% had in-hospital SSI. Mean prediction day for patients who developed SSI vs. no SSI: 7.25 vs. 7.29. Univariate analysis of SSI vs. non-SSI groups showed differences in c-reactive protein (5.3 – 8.4 vs. 2.6 – 5.9 mg/dL, p < 0.05), surgery duration (308 – 148 vs. 253 – 124 min, p < 0.05) and
contamination (dirty cases 21 [11.8%] vs. 25 [3.9%], p < 0.001), but no differences in ASA scores, diabetes, or emergency surgery. Classifier performance is compared in Table 1. In order, the most predictive features in the RF classifier were granulation score, pulse rate, presence of NG tube, amount of exudate, wound culture ordered, and wound separation distance. Conclusions: Repeated features provided moderate PPV and high NPV for prediction of SSI in advance of clinical diagnosis. Addition of baseline patient/operative data did not improve prediction. Features of evolving SSI are discernable prior to the day of diagnosis based primarily on visual inspection.
O37. COMPONENT SEPARATION VERSUS BRIDGED REPAIR FOR LARGE VENTRAL HERNIAS: A MULTI-INSTITUTIONAL RISK ADJUSTED COMPARISON Julie Holihan, Ioana Bondre, Erik Askenasy, Jacob Greenberg, Jerrod Keith, Robert Martindale, John Roth, Curtis Wray, Lillian Kao, Mike Liang, University of Texas Health Science Center at Houston Background: Ventral hernia repair (VHR) of large defects (width ‡ 8 cm) is associated with high rates of surgical site infection (SSI) and recurrence. Two operative strategies exist: Component separation with primary fascial closure and mesh reinforcement (CS) and bridged repair (mesh spanning the hernia defect). CS creates a functional abdomen and protects the mesh with a vascularized, functional barrier. Bridged repairs avoid high-risk skin flaps and require less operative time. Few studies have compared outcomes between these options. Hypothesis: VHR of large defects with CS is associated with more SSIs but fewer recurrences than bridged repair. Methods: A multi-center database of patients with VHR from 2010–2011 was queried for patients with at least 1 mo of follow up and a defect ‡ 8 cm. CS repairs were compared to bridged. Univariate and multivariable stepwise regression were performed to identify factors associated with SSI and recurrence. Subgroup analysis was performed of patients undergoing elective repair. Results: 129 VHR were followed for a median of 17 (1–48) mos: 84 underwent CS and 45 had bridged repair. Between the two cohorts, there were differences in patient and hernia characteristics (Table). Unadjusted results demonstrated a clinically important but statistically non-significant difference in SSI and recurrence. There were fewer deep/organ space SSIs with CS. By multivariable analysis, there was a trend toward fewer SSIs (OR 2.2, 95%CI 0.7-6.8) and recurrences (OR 2.1, 95%CI 0.9-5.1) with CS. On subgroup analysis of elective VHR only (n = 114), multivariable analysis showed fewer SSI with CS (OR 2.7, 95%CI 1.1-6.8). The multivariable model for recurrence in elective repairs did not converge. Conclusions: In this multi-center study, CS had fewer SSIs—particularly deep and organ/space SSI—and recurrences compared to bridged repair of large ventral hernias. While these differences were not statistically significant, CS may be a more suitable option for large VHR. Future studies should compare the risks and benefits of these repairs in similar patient populations to determine in which settings CS and bridged repair are best utilized.
S-20 O38. CLINICAL DIAGNOSIS OF INFECTION IN SICU: YOU ARE NOT AS GOOD YOU THINK! Madhu Subramanian, Sara Hennessy, Malcolm MaCConmara, Carol Hirschkorn, Joseph Minei, Robert Sawyer, Christian Minshall, Tjasa Hranjec, University of Texas Southwestern Medical Center Background: The National Healthcare Safety Network and Centers for Medicare and Medicaid Services (CMS) require reporting of hospital-acquired infections. Accurate identification of infections by surgical intensivists is of great importance for patient care, monitoring, and hospital reimbursement. Hypothesis: We hypothesized that physicians are able to differentiate clinically between infected and non-infected patients, leading to appropriate treatment. Methods: Between 12/13-07/14, all potentially infected patients in surgical ICU were included in our prospective study. When patients were suspected of having an infection based on clinical grounds, cultures were obtained. Three most-senior physicians were required to independently answer a questionnaire about possible infectious diagnosis, etiology of disease, and indications for treatment with antibiotics. Questionnaire and culture data were compared. Results: Fifty-two critically ill patients presented with signs and symptoms of infection, with 156 (3 per patient) independent physician evaluations generated. Physicians correctly diagnosed patients as either infected or non-infected 53% of the time. Percent of overall agreement between reviewers on the correct diagnosis was poor (kappa = 0.33). Based on objective evidence, all 3 physicians were correct 27% of the time and incorrect 23% of the time. In infected patients, physicians correctly predicted the source of infection 60% of the time. In non-infected patients, physicians predicted negative culture results 36% of the time (Sensitivity = 59.3%, Specificity = 64.4%, PPV = 80%, NPV = 39.7%). For patients with more than one infection, a second source of infection was diagnosed correctly 26.7% of the time. Physicians were most accurate in predicting ventilator-associated pneumonia, followed by blood stream and intraabdominal, then urinary tract infections. Based on our ICU antibiotic protocols and physician action on culture results, antibiotics were initiated appropriately 78% of the time - 83% of the time in infected patients. When treatment was determined solely based on clinical judgment, antibiotics were initiated correctly 50% of the time, 39% in infected patients. Conclusions: Even in the hands of the most experienced clinicians, infected patients can be identified accurately 50% of the time and furthermore there is poor agreement among clinicians. In the critically ill patient, an infectious diagnosis should always be accompanied by obtaining cultures, since clinical diagnosis is difficult and often inaccurate.
O39. CHARACTERIZATION OF THE MURINE SEPTIC RESPONSE USING WIRELESS TELEMETRY TECHNOLOGY Anthony Lewis, Christopher Seymour, Du Yuan, Matthew Rosengart, University of Pittsburgh Background: Murine models are commonly utilized in the study of sepsis to test experimental treatments that are administered at fixed intervals after the insult. Yet, sepsis care in human beings is prompted not by time on the clock, but by physiologic and behavioral changes that prompt medical care. These animal models ignore the inherent variability in the magnitude and temporality of the host response. Thus, animal models of time-based treatment lack any realistic clinical correlate. We sought to better characterize the murine septic response to cecal ligation and puncture (CLP) with novel wireless telemetry technology. Hypothesis: We hypothesize that the murine septic response will show a range of variability in mice subjected to cecal ligation and puncture.
ORAL PRESENTATION ABSTRACTS Methods: C57BL/6J mice aged 8–12 weeks were assigned to either control or CLP groups. CLP was performed using a 1-cm ligation/double 21-ga puncture method. At the time of CLP, mice in both groups were implanted with a HD-X11 wireless telemetry monitor (Data Sci Intl.). This device enables continuous monitoring of core temperature, ECG, and animal foraging activity. Mice were observed and parameters monitored for 24 h. Results: During the 24-h observational period, control mice showed fairly consistent and similar post-procedure recovery and return to physiologic baselines (Fig. 1). By contrast, mice subjected to CLP showed considerable heterogeneity in thermoregulation, cardiac physiology, and the sick response to the insult (Fig. 1). Responses of mice in the CLP group ranged from death within the first 16 h to mild illness with near-normal vital signs and activity levels. Additionally, mice subjected to CLP began to develop sepsis at a variety of time points after surgery. Conclusions: Considerable heterogeneity in the murine response to CLP sepsis was observed. The testing of experimental treatments at fixed time points after insult ignores this variability. The use of continuous wireless telemetric monitoring may enable us to conduct future studies that test treatments at more physiologically relevant time points and that provide data of greater clinical relevance to, and thus guidance of, human trials.
O40. LACTOBACILLUS PROBIOTIC SPECIES STRENGTHEN INTESTINAL BARRIER FUNCTION AND TIGHT JUNCTION INTEGRITY Brian Blackwood, Carrie Yuan, Joseph Nicolas, Douglas Wood, Catherine Hunter, Ann and Robert H. Lurie, Children’s Hospital of Chicago, Northwestern University Feinberg School of Medicine Background: Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency of premature infants. Probiotics have shown efficacy in the prevention of NEC, but the underlying mechanisms remain unknown. Tight junctions (TJ) are protein complexes that maintain epithelial barrier integrity. Hypothesis: We hypothesized that Lactobacillus sp. (rhamnosus (LR) and plantarum (LP)) strengthen intestinal barrier function, promote TJ integrity, and protect against experimental NEC. Methods: Monolayers of polarized intestinal epithelial cells (Caco-2) were pretreated with various doses of LR and LP. Trans-epithelial resistance (TER) was measured over a time course. TJ were disrupted by 1) EGTA calcium switch, or 2) LPS treatment. The ability of LR and LP to maintain TER was measured. Transmembrane flux of fitc dextran assessed permeability. TJ structure was evaluated by ZO-1 immunofluorescence. The in vivo effect of Lactobacillus was assessed with the Cronobacter sakazakii (CS) rat pup model of NEC. Pups were subject to hypoxia and CS-formula feeding – LR. The enteral: serum ratio of gavaged fitc dextran was measured. Intestinal segments were processed for histology and protein analysis. Intestinal injury scores were measured by a blinded pathologist. Differences were analyzed with ANOVA. Results: TER increased by 163 ohms (62%) when treated with LR, and by 20 ohms (8%) when treated with LP (p < 0.01, p < 0.05). Cells treated with LP and LR had decreased permeability to fitc dextran (p < 0.0001). ZO-1 immunofluorescence confirmed TJ structural stability in cells that received probiotic treatment compared with controls. Pup intestinal injury scoring revealed a significant decrease in intestinal injury in the pups that received Lactobacillus sp. compared to controls (p < 0.03). There was a significant increase in permeability to fitc dextran in those pups that did not receive probiotics as compared to those that did (p < 0.0004). Conclusions: Lactobacillus sp. strengthen intestinal barrier function and preserve TJ integrity in experimental models of NEC. The mechanisms by which this effect takes place represent an exciting area of future research.
ORAL PRESENTATION ABSTRACTS O41. MESENCHYMAL STEM CELLS REVERSE ANEMIA AND BONE MARROW DYSFUNCTION FOLLOWING TRAUMA, HEMORRHAGIC SHOCK, AND CHRONIC STRESS Amy Gore, Letitia Bible, David Livingston, Alicia Mohr, Ziad Sifri, Rutgers UniversityNJ Medical School Background: Animals undergoing lung contusion (LC) followed by hemorrhagic shock (HS) and daily chronic stress (CS) exhibit persistent bone marrow (BM) dysfunction and anemia lasting up to 7d following injury. Hypothesis: Given the protective immunomodulatory effects of mesenchymal stem cells (MSCs), we hypothesize that MSCs can attenuate BM dysfunction and anemia following LCHS/CS. Methods: Male Sprague-Dawley rats (n = 6/group) were subjected to LCHS/ CS – single IV dose of 5X106 allogeneic MSC. Animals underwent 2 h of daily restraint stress until sacrifice (d 7). BM cellularity and growth of hematopoietic progenitor cell (HPC) colonies (CFU-E, BFU-E, and CFU-GEMM) were analyzed. Peripheral blood (PB) was collected for hemoglobin analysis, flow cytometry for HPCs, and plasma G-CSF level by ELISA. Data were analyzed by one-way ANOVA followed by Tukey multiple comparison test. Results: Treatment with MSCs post LCHS/CS resulted in a 31% increase in BM cellularity as compared to LCHS/CS alone. Similarly, there were 53%, 63%, and 59% increases in CFU-E, BFU-E, and CFU-GEMM, respectively. This was associated with an increase in hemoglobin by 27%. Furthermore, MSC administration resulted in a 77% decrease in the number of HPCs mobilized to the periphery and 132% decrease in plasma G-CSF level. Conclusions: The administration of a single dose of MSCs post injury reverses the persistent anemia, HPC mobilization, G-CSF elevation, and BM dysfunction seen 1 wk following LCHS/CS. Further study into the immunomodulatory effects of MSCs following trauma, shock, and chronic stress is warranted.
O42. REMOTE ISCHEMIC PRECONDITIONING PLASMA PREVENTS NEUTROPHIL INFILTRATION BY INCREASED ANTI-OXIDATIVE CAPACITY IN THE ZEBRAFISH Chung Ho Leung, Stephen Lam, Xiao-Yan Wen, Christopher Caldarone, Ori Rotstein, University of Toronto, St. Michael’s Hospital Background: Oxidative stress and neutrophil infiltration following hemorrhagic shock contribute to organ dysfunction in trauma patients. We have previously reported that transient ischemia/reperfusion in the limb known as remote ischemic preconditioning (RIPC) attenuates lung and liver injury in a murine model of hemorrhagic shock. Further, RIPC liberates humoral factors in the plasma that reduces neutrophil infiltration in a zebrafish model of tailfin injury. We hypothesized that plasma from RIPC animals might exert an anti-oxidant effect as a mechanism leading to reduced neutrophil migration in the zebrafish. Hypothesis: RIPC plasma prevents neutrophil infiltration through up-regulation of anti-oxidative capacity. Methods: C57BL/6 mice were subjected to RIPC by occlusion of the left hindlimb with a tourniquet for four cycles of 5-min ischemia and 5-min reperfusion. Control or RIPC plasma were collected and microinjected into 3 d-post-fertilization Tg(mpx:EGFP) zebrafish. In these fish, neutrophils are labeled with GFP. After 18h, complete tailfin transection was performed. Neutrophil infiltration at the transected area was assessed at peak migration and reactive oxygen species (ROS) production at the site of injury was assessed over a time course using the CellROX DeepRed fluorescent dye. Fluorescence imaging was used to study neutrophil migration and oxidative stress. Data are shown as mean – SEM of n determinations. Results: Tailfin transection in zebrafish microinjected with control plasma resulted in a significant rise in ROS production at the site of injury, which peaked at 55 to 65 min post-transection (1,024,711 – 153,172 MFI, n = 3) and neutrophil infiltration (12 – 2, n = 6). By contrast, zebrafish microinjected with RIPC plasma had significantly lower ROS production compared to zebrafish microinjected with control plasma (714,777 – 103,254 MFI, n = 3, p < 0.05) and significantly lower neutrophil count (5 – 1, n = 6, p < 0.01). In support of the conclusion that reduction of neutrophil migration was related to the anti-oxidant effect of RIPC plasma, administration of anti-oxidant N-acetylcysteine prior to tailfin transection prevented the ROS production and subsequent neutrophil infiltration. Conclusions: ROS is a chemokine that mediates neutrophil migration in the zebrafish. RIPC liberates humoral factor(s) that may prevent neutrophil infiltration through attenuation of local ROS production. Induction of antioxidant capacity represents a novel mechanism underlying the anti-inflammatory effect of RIPC.
O43. PSEUDOMONAS AERUGINOSA INFECTION AUGMENTS BURNINDUCED HEPATIC ER STRESS Mile Stanojcic´, Bogdan Stankovic´, Marc Jeschke, University of Toronto, Sunnybrook Research Institute Background: Thermal injury is a trauma that is characterized by a severe hypermetabolic response and increased susceptibility to infection if not resolved. The unfolded protein response (UPR) initiated by the endoplasmic reticulum (ER) is an adaptive process to manage organelle stress, preventing further dysfunction. Activation of the
S-21 UPR/ER stress response pathway has been implicated in promoting a persistent hypermetabolic response following thermal injury by not facilitating but rather promoting infections. Hypothesis: Using the two-hit model of burn + Pseudomonas aeruginosa (PA) infection, we sought to investigate the activation of this signaling pathway in a timedependent manner during the pathogenesis of injury. Methods: Mice were divided into three treatment groups (control, burn, and burn + PA infection). Burned mice received a full-thickness, 30% scald burn (98C for 10 sec), with infectious mice receiving PA topically at a dose of (1-1.5x107 CFU), 3 d after insult. All mice were sacrificed during the following time points with respect to insult, (relative to burn for the burn group and infection for burn + PA group): 1, 12, 24, and 48 h. Multiplex analysis was used to characterize chemokine and inflammatory cytokine expression. Results: Here we show that both burn and burn + infection groups have distinct and time-dependent hepatic ER stress activation profiles. Specifically, both groups had upregulation of all markers relative to controls with characteristic expression observed for BiP, PERK, JNK and eIF2a at all time points (1, 12, 24, and 48 h after insult, respectively). The infectious burn group was best distinguished by BiP with elevated expression present during the acute time points and peaking at 12 h; 4.8- and 2.2-times higher than controls (p < 0.01) and burn (p < 0.05), respectively. Chemokines began to distinguish themselves at 12 h after infection with elevated expression at 24 h (G-CSF, MCP-1, KC, MIP-1a/b, MIP-2). Similarly, inflammation was also elevated at the 24 h mark relative to both control and burn mice (TNF- a & IL-1b). Conclusions: Our findings indicate that burn + PA infection results in augmented hepatic ER stress and highlights further the importance of selecting appropriate time points and pathways to best reflect the phenotype. Furthermore, the time-dependent immune responsiveness suggests that hepatic ER stress may be driving the systemic inflammatory response. Therapeutic interventions need to be further explored to determine the impact of alleviating this response following injury, which may act to minimize systemic pathology.
O44. COMPUTED TOMOGRAPHY VERSUS ULTRASOUND FOR THE DIAGNOSIS OF ACUTE CHOLECYSTITIS Eva Fuentes, Peter Fagenholz, Haytham Kaafarani, Catrina Cropano, David King, Marc De Moya, Kathryn Butler, George Velmahos, Daniel Yeh, Harvard Medical School, Massachusetts General Hospital Background: Ultrasound (US) is the first-line diagnostic study for evaluating gallstone disease and is considered the test of choice for diagnosing acute cholecystitis (AC). However, computed tomography (CT) is widely used for the evaluation of abdominal pain and is often obtained as a first abdominal imaging test, particularly in cases in which typical clinical signs of AC are absent, or other possible diagnoses are being considered. Hypothesis: We hypothesized that CT is more sensitive than US for diagnosing AC, and that if CT shows AC, a US is not needed to confirm the diagnosis. Methods: A prospective registry of all urgent cholecystectomies performed by our Acute Care Surgery service between June 2010 and January 2014 was queried for cases of AC. Patients were classified into two groups according to pre-operative radiographic work-up: US only, or CT and US. The final diagnosis was based on operative findings and pathology. Results: A total of 209 patients underwent cholecystectomy for AC. All patients underwent US and 57 (27%) also underwent CT. In the subgroup undergoing both CT and US the sensitivity of US was 82% (47/57) compared to 93% for CT (53/57) (p = 0.15). US and CT agreed on the diagnosis of AC in 45 cases (79%). In the remaining 12 patients, the diagnosis of AC was missed by US in 8 patients (14%), missed by CT in 2 patients (3%), and missed by both in 2 patients (3%). Patients undergoing US and CT were more likely to be male, older, have medical comorbidities, were less likely to have typical signs and symptoms of AC, and more likely to have systemic manifestations such as fever and leukocytosis (Table). Conclusions: CT often diagnoses AC in patients with atypical clinical signs, and US is not needed to confirm the diagnosis. CT may be more sensitive than US for the diagnosis of AC, although this requires further investigation in larger studies.
S-22 O45. COMPARISON OF SCREENING TOOLS’ ABILITY TO DETECT SEPSIS ACCURATELY Richard Wawrose, Mary Baraniuk, Lauren Standiford, Charles Wade, John Holcomb, Laura Moore, The University of Texas Health Science Center at Houston Background: Sepsis is still the primary cause of perioperative mortality and the leading cause of death in non-cardiac intensive care units. In order to reduce sepsis-related morbidity and mortality, it is crucial that healthcare workers recognize and treat sepsis early. To address this issue, the Surviving Sepsis Campaign guidelines advocate for sepsis screening. However, there is little information in the current medical literature to suggest which sepsis screening tool is optimal. The purpose of this study was to compare a sepsis screening tool that we have validated previously and published, the Sepsis Screening Score (SSS), with a commercially available sepsis screening tool, the St. John’s Sepsis Alert (SJSA) developed by Cerner. Hypothesis: The SSS can detect sepsis more accurately than the SJSA. Methods: This prospective observational study compares the accuracy of the SSS with that of the SJSA in the same patient population. The SSS was performed on each patient in our surgical intermediate care unit (SIMU) twice daily. The SJSA continuously monitored these same patients for sepsis via the EMR. Epidemiologic data related to sepsis were collected prospectively, and the performance characteristics of the two tests were compared using the two-proportion Z-test. Results: A total of 276 patients (50.4% male, Average Age = 52.9 y (Range 16–100 y)) were included in the study, and 47 (19.9%) of these patients developed sepsis. Of the septic patients, the sources of infection were 13.3% intra-abdominal, 7% skin/soft tissue, 13% UTI, 18% pneumonia, 14% blood, 4% surgical implant, and 31% culture-negative. The performance characteristics of the two tests are displayed in the table. Conclusions: Despite the fact that SJSA had constant surveillance over patients’ EMRs, it still detected fewer septic patients than the SSS, which was performed twice a day. The difference in sensitivities and NPVs between the two tests is of particular importance, as this indicates that the SJSA is more prone to missing the diagnosis of sepsis. This study establishes a basis for the utilization of the SSS instead of the SJSA.
ORAL PRESENTATION ABSTRACTS Conclusions: Culture-positive BAL samples exhibited a more robust immune response and reduced diversity of bacterial species. Lower cytokine levels in culturenegative samples, despite a greater number of bacterial species, suggests a diverse resident non-pathogenic bacterial community may be indicative of a healthy environment.
O47. THE TRANSITION FROM A RURAL TO URBAN ENVIRONMENT IN AFRICA ALTERS THE EXPRESSION OF GENES INVOLVED IN CHOLESTEROL METABOLISM: POTENTIAL IMPLICATIONS FOR SUSCEPTIBILITY TO INFECTIOUS DISEASES Radhames Lizardo, Simone Langness, David Cauvi, Katherine Davenport, Julia Grabowski, Antonio De Maio, Stephen Bickler, University of California-San Diego, Rady Chilidren’s Hospital, San Diego Background: We have recently reported that expression of the Niemann-Pick C1 (NPC1) protein, the receptor of the Ebola virus, is higher in rural compared to urban populations living in Africa. NPC1 is a transmembrane endosome protein responsible for the transport of internalized cholesterol in other intracellular compartments. We have speculated NPC1 expression is down-regulated in urban populations from either reduced rates of infection or increased ingestion of fat. In this report, we expand this research and examine whether other genes that regulate cholesterol metabolism are altered in the transition from a rural to urban environment in Africa. Hypothesis: The transition from a rural to an urban environment in Africa alters the expression of genes that control cholesterol hemostasis. Since cholesterol metabolism pathways are known to play a role in innate immunity; variance in their expression could predispose to infectious susceptibilities. Methods: We queried gene array data from a study by Igadahor et al. (2008) that examined gene expression in peripheral blood leukocytes of genetically similar nomadic, rural, and dense urban Moroccan Amazigh populations (NCBI, GSE8847). Genes involved in cholesterol metabolism were identified by a literature review. The analysis was performed using the NCBI GEO2R tool with results expressed as an adjusted p value. An adjusted p < 0.05 was considered statistically significant. Results: Twenty genes that control cholesterol metabolism were examined. Of the genes analyzed, five had higher expression in rural compared urban populations: NPC2, LDLR, SREBPF2, NR1H3 and SCARB1/SCARB2. These genes are involved in both sterol homeostasis and innate immunity. LDLR and SCARB1 have a role in viral infection such as hepatitis C and the NPC family in ebola virus infection. SREBPF2 and NRIH3 are important mediators of the inflammatory response to bacterial infections. Conclusions: Our data illustrates the important role environmental factors have in altering the expression of genes that control cholesterol metabolism which are now well known to have a critical role in the immune response to a variety of pathogens. Further, our findings could provide important insight into factors that determine susceptibility to both communicable and non-communicable diseases in a variety of populations.
O46. PULMONARY MICROBIOME AND CYTOKINE ANALYSIS OF BRONCHOALVELOAR LAVAGE IN MECHANICALLY VENTILATED TRAUMA PATIENTS
O48. IMPACT AND PROGRESSION OF ORGAN DYSFUNCTION IN PATIENTS WITH NECROTIZING SOFT TISSUE INFECTIONS; A MULTICENTER STUDY
Ryan Huebinger, Deborah Carlson, Ashley Smith, Sara Ireland, Ding Chen, Christian Minshall, Joseph Minei, Robert Barber, Michael Allen, Steven Wolf, Nancy Monson, University of Texas Southwestern Medical Center
Eileen Bulger, Addison May, Sharon Henry, Adrian Maung, Kevin Foster, David Evans, Andrew Bernard, Jacob Quick, Stephen Cohn, Therese Duane, Robert Sawyer, Irit Segalovich, Gregory Maislin, David Smith, Leslie Kobayashi, Wayne Dankner, Anat Shirvan, AtoxBio, Ltd., Ness Ziona, Israel
Background: Mechanically ventilated patients have a variety of bacterial lung flora that are often undetectable by traditional culture methods. The source of infection in many of these patients remains unclear. To better address this problem clinically, we have used next-generation sequencing to query the lung microbiome of such patients as a means to identify the source of infection. Expanding on our previous immunophenotyping and microbiome work we examined the levels of cytokine production in BAL fluid within this patient cohort. Hypothesis: Levels of cytokine response will differ in BAL samples based upon the presence of a predominant bacterial pathogen identified by traditional culture and microbiome sequencing. Methods: Bronchoalveolar lavage samples were collected in the SICU as a part of standard of care for intubated individuals that had a CPIS > 6 or would be intubated > 48 h (screening). Raw BAL was frozen at - 80C for microbiome analysis. The remaining BAL fluid was filtered through a 70-micron filter and centrifuged to pellet cells. BAL supernatant was stored at - 80C for cytokine analysis. Cytokine analysis was conducted with the Bioplex Pro Human Th17 cytokine panel (15-plex). The microbiome of BAL samples were sequenced for the 16S rRNA region using the ION Torrent PGM. Bacterial species with a relative abundance of less than 1% were excluded from the microbiome profile. Results: A total of 8 culture positive and 6 culture negative BAL samples were analyzed. Five of the 6 culture negative BAL samples were screening BALs. Microbiomes of the culture-positive BAL were dominated by one or two pathogens. The average number of species in the culture-positive BAL (with relative abundance > 1%) was 3.4 species, whereas the culture-negative BAL had an average of 17.3 species (with relative abundance > 1%) and were not dominated by a single bacterial species. Comparison of cytokine expression (represented as pg/mL) between the culture-positive and -negative BAL showed an increased level of cytokines in culture-positive samples: Interferon-gamma (15.4 vs. 0.6), IL-17F (20.7 vs. 2.0), IL-1 beta (1189.9 vs. 9.3), and IL-6 (417.0 vs.114.8) (culture-positive vs. culture-negative).
Background: Necrotizing soft tissue infections (NSTI) represent a rare but devastating disease for which the systemic manifestations have been poorly characterized. In an effort to define an optimal endpoint for clinical trials, the objective of this study was to establish the pattern of organ dysfunction over time and determine the relationships between organ dysfunction and clinical outcome. Hypothesis: We hypothesized that organ dysfunction on admission and failure of resolution of organ dysfunction would both be associated with poor outcome.
ORAL PRESENTATION ABSTRACTS Methods: This was a multicenter, retrospective study of NSTI patients presenting to 12 US academic medical centers in 2013. Patients with a surgical diagnosis of NSTI without prior debridement were included. Organ dysfunction was assessed using the modified SOFA score (mSOFA: excluding liver) on admission and on hospital days 1, 2, 3, 7, 10, and 14. The presence of organ dysfunction on admission and resolution of organ dysfunction were correlated with ICU-free days (of 28 d), ventilator-free days, number of debridements, and mortality. Results: 198 patients were enrolled, 62% male, mean age 51yrs, 40% monomicrobial. The mean mSOFA score on admission was 2.4 – 3.0 with 49% presenting with mSOFA ‡ 2.0 and 35% with mSOFA ‡ 3. Patients demonstrated worsening of the mSOFA score over the first 24 h followed by gradual resolution (Fig.). A mSOFA ‡ 2 at admission was associated with a significant decrease in ventilator-free days (mean 26.9 vs. 21.4 d, p < 0.001), and ICU-free days (24.1 vs. 16.6 d, p < 0.001), more debridements (mean 1.9 vs. 2.4, p = 0.01) and higher mortality (2.0% vs. 13.3%, p = 0.006). The persistence of organ dysfunction (mSOFA > 1) among survivors at d14 was also associated with fewer ICU-free days (17.8 vs. 23.6 d, p < 0.001) and ventilator-free days (23.6 vs. 27.0 d, p = 0.001). Conclusions: Early development of systemic organ dysfunction in patients with NSTI is associated with higher morbidity and mortality. Failure of resolution of organ dysfunction by14 d is also associated with poor outcome. mSOFA score may be a useful marker for patient selection for inclusion in interventional trials and the resolution of organ dysfunction by day 14 may be an important clinical endpoint.
Poster Presentation Abstracts
P01. BILE ACID PROFILING BY LIQUID CHROMOTOGRAPHY-TANDEM MASS SPECTROMETRY IN NEONATES WITH NECROTIZING ENTEROCOLITIS Anne Roberts, Anastasia Kalli, Xiaowei Fu, Henri Ford, Christopher P. Gayer, University of Southern California, Children’s Hospital Los Angeles Background: Necrotizing enterocolitis (NEC) is a severe intestinal disorder of premature infants. Intestinal bacteria convert liver-generated primary bile acids into more toxic secondary metabolites. Animal models suggest that secondary bile acids can induce intestinal damage similar to NEC. Liquid chromatography and tandem mass spectrometry (LC-MS/MS) can be used to measure the concentration of specific bile acid metabolites in a clinical setting. Hypothesis: We hypothesize that LC-MS/MS is a useful tool for measuring bile acids clinically in patients with NEC. Furthermore, we hypothesize that patients with NEC will have elevated levels of secondary bile acids in serum. Methods: Serum samples were collected from patients with NEC at the time of diagnosis for up to 10 wks. Using 50 mcL of serum, we isolated bile acids using methanol extraction followed by centrifugation. The supernatant was dried under a nitrogen stream and re-suspended in methanol. LC was performed in MRM mode over a 12-min elution time on a Kinetex C18 column. Nineteen bile acid standards were optimized. Two deuterized internal standards and their calibration curves were used to calculate sample concentrations. Results: A total of 7 patients with NEC were included, 3 treated surgically and 4 treated medically. In patients successfully treated medically, no secondary bile acids were identified in serum during the 2 wks of treatment. In the patient who failed medical management, we identified increased secondary bile acids for 4 d leading up to surgical intervention. These metabolites disappeared after successful treatment. In the patients treated surgically, normal primary bile acids levels increased post-resection corresponding to clinical recovery. Conclusions: LC-MS/MS is effective at measuring, monitoring, and quantifying bile acid profiles in patients with NEC with only 50 mcL of serum. Our results indicate that secondary bile acids are elevated in the serum of patients with NEC. Post-treatment, this is replaced by normal primary bile acids. LC-MS/MS may be a useful clinical tool in the diagnosis of NEC, where bacterial changes lead to production of harmful bile acid metabolites.
P02. TAURINE-CONJUGATED CHOLIC ACID PROMOTES INTESTINAL CELL PROLIFERATION BY ACTIVATING THE MEMBRANE RECEPTOR TGR5 Avafia Dossa, Anne Roberts, Henri Ford, Christopher P. Gayer, University of Southern California, Children’s Hospital Los Angeles Background: Changes in the composition of bile acids by intestinal bacteria may contribute to diseases such as necrotizing enterocolitis. Previously, we have shown that the primary bile acid taurocholic acid (TCA) stimulates intestinal epithelial cell proliferation, whereas deoxycholic acid (DCA), a secondary bile acid generated by bacterial modification of TCA, inhibits it. The G-protein coupled receptor TGR5 is known to bind bile acids and can transactivate EGFR via Src kinase and matrix metalloproteinases (MMP). Hypothesis: Since we have shown that TCA functions through a Src- and EGFRdependent mechanism, we hypothesize that TCA promotes intestinal proliferation via upstream TGR5 activation. Methods: Rat intestinal epithelial cells (IEC-6) were subjected to DCA or TCA treatment and proliferation was measured using crystal violet staining and nucleic acid incorporation (EdU). TGR5 was activated by a natural agonist oleanolic acid and inactivated by TGR5-specific siRNA transfection. MMP was inhibited pharmacologically with TAPI-1. Results: Oleanolic acid (12.5 mcM) treatment led to an increase in IEC-6 cell proliferation in a dose-dependent manner (33.1%, p = 0.020). DCA treatment abolished the proliferative effects of oleanolic acid. TCA stimulated proliferation in cells treated with non-targeting siRNA as expected (32.8%, p = 0.043), but this effect was blocked by TGR5-specific siRNA knockdown. Transfection efficiency and protein knockdown was approximately 82% and 71% as assessed by fluorescence siRNA control and immu-
noblotting, respectively. Pre-treatment with TAPI-1 did not block the proliferative effects of TCA. Conclusions: These data suggest that TCA exerts its proliferative effects on intestinal epithelial cells via TGR5 activation, independent of MMP activation. DCA treatment can overcome these effects through a separate mechanism. Understanding how specific bile acid metabolites interact with the intestine may provide a mechanism by which an altered microbiome contributes to disease.
P03. CHANGES IN THE CARDIAC INFLAMMASOME FOLLOWING SEPTIC INSULT RELATED TO INFLAMMATION Deborah Carlson, Hailey Wolf, Xiao Yao, Steven Wolf, University of Texas Southwestern Medical Center Background: Severe inflammation following sepsis is common. The inflammasome is a multi-protein complex comprising caspase-1, adaptor protein apoptosis-associated speck-like protein containing a caspase-activating recruitment domain protein (ASC), and the sensor NLR. It has been identified as one of the key components of the innate immune response. Inflammasomes contain specific NLR proteins, namely NLRP1, NLRP2, NLRP3, NLRP6, NLRP7, NLRP12, or NLRC4. Hypothesis: The aim of this study was to examine the response of the inflammasome to septic insult and the associated specific NLR factors in the heart. Methods: Male C57/BL6 mice were divided into two groups. One group was treated as a control and one group was injected IP with 4 mg/kg of Escherichia coli 0111:B4 lipopolysaccharide (LPS) in a total of 0.5 mL, or PBS. Mice were sacrificed and both serum and heart samples were taken at time 0, 30 min, and 1, 2, 4, and 8 h after injury. Heart protein was prepared for immunoblot with antibodies for NLR factors, ASC, and both inactive and active caspase-1. Serum was used to correlate inflammation via ELISA monitoring activity of TNF, IL-1, IL-6, and IL-10. Results: Immunoblot analysis revealed that in all control animals, despite the time of harvest, no significant difference was found in expressed ASC or NLRP1 in cardiac tissue; NLRP3 was not expressed. In comparison, by 30 min after septic insult, the level of ASC had tripled in the cardiac tissue, and the amount of NLRP1 had decreased by 4.5%. In addition to NLRP1 changes, following injury we detected NLRP3 in cardiac tissue as well as active caspase-1. The predominant NLR at 4 and 8 h was NLRP3, a complete switch from predominate NLRP1 found prior to injury. Serum samples were tested by ELISA to correlate inflammation with the observed changes in the cardiac inflammasome. TNF peaked at 30 min after injury (45 – 1.9 pg/mL control vs. 382 – 528 pg/mL burn). Similar increases in both IL-6 and IL-1 were also observed, with IL-1 demonstrating the latest peak at 8 h (32 – 2 pg/mL control vs. 380 – 7 pg/mL burn). Conclusions: In the heart, in response to septic insult a shift in expression from the NLRP1 sensor to NLRP3 occurred. This shift in expression correlated with an increase in active caspase-1 as well as an increase in markers of inflammation including TNF, IL-1, and IL-6. From these data we conclude that upon stimulation by injury, sensor proteins in the inflammasome shift, triggering activity and associated production of active cytokines.
P04. UDCA INDUCES ENTEROCYTE MIGRATION VIA EGFR AND COX-2 DEPENDENT MECHANISMS Jamie Golden, Avafia Dossa, Patil Kavarian, Henri Ford, Christopher Gayer, University of Southern California, Children’s Hospital Los Angeles Background: The secondary bile acid, ursodeoxycholic acid (UDCA), plays an important role in intestinal epithelial cell signaling. Previous work in our lab has shown that UDCA promotes enterocyte migration via the epidermal growth factor receptor (EGFR). COX-2 and its product, prostaglandin E2 (PGE2), are key mediators of enterocyte cell signaling and act on 4 G-protein coupled receptors (EP1-4). EP2 and EGFR have been identified as receptors that promote enterocyte migration. Hypothesis: We hypothesized that UDCA promotes enterocyte migration via both EGFR- and COX-2-dependent mechanisms. Methods: Rat intestinal epithelial cells (IEC-6) and mouse colon cells derived from an EGFR knockout mouse transfected with either a human EGFR plasmid (MCE WT) or an empty vector (MCE -/-) were used. COX-2 expression was determined by Western blot. Cell migration was measured in IEC-6 cells using a modified wound-healing assay by
POSTER PRESENTATION ABSTRACTS creating circular holes in cell monolayers and observing them over 6 h. Cells were treated with UDCA with or without pharmacologic inhibitors to EP2, COX-2, and EGFR. Results: UDCA significantly increased COX-2 expression in IEC-6 cells in a dosedependent manner at doses greater than or equal to 10 mcM. UDCA at 200 mcM increased COX-2 expression 2.7-fold compared to control (p < 0.05). Pre-treatment with an EGFR inhibitor (AG-1478) blocked UDCA-mediated induction of COX-2. UDCA at 200 mcM induced COX-2 expression 2.1-fold compared to control in MCE WT cells but did not induce COX-2 expression in MCE -/- cells. UDCA at 200 mcM increased wound closure 18.0 – 0.2% from control (p < 0.05). Pre-treatment with EP2 antagonist (PF-04418949) or COX-2 inhibitor (Rofecoxib) significantly inhibited UDCA-induced IEC-6 migration. Conclusions: Our data indicate that UDCA induces COX-2 expression in an EGFRdependent manner and that UDCA-induced stimulation of intestinal epithelial cell migration is blocked by a COX-2 inhibitor and by an EP2 receptor antagonist. These data suggest a novel role for an EGFR-COX-2-EP2-dependent pathway in UDCA-induced stimulation of enterocyte migration. This may represent a novel pathway to enhance epithelial restitution after injury.
P05. CHARACTERIZATION OF GLIAL ACTIVITY IN THE BRAIN OF YOUNG AND AGED ANIMALS SUFFERING FROM MILD TBI Joshua Gatson, Ming-Mei Liu, MS, Joseph Minei, Steven Wolf, University of Texas Southwestern Medical Center Background: Following a mild traumatic brain injury (TBI) event, the secondary BI that persists after the initial blow to the head consists of excitotoxicity, heightened inflammation, neuronal cell death, and cognitive/mood disorders. With respect to inflammation, shortly after TBI, the immune system becomes hyperactive and results in an exacerbated activation state of glia (microglia/astrocytes) in the brain. In both young and aged animals, the primary objective of this research was to characterize the activation pattern of microglia and astrocytes in the cerebral cortex during the acute and chronic phases after mild TBI. Hypothesis: Glial cell activity is decreased in the brain of aged animals 30 d after mild TBI. Methods: In this study, male mice were injured using the controlled cortical impact device. Using a closed-head mild TBI model, a midline incision was made to access the skull and the impactor tip was aligned directly on the skull on the sagittal suture midway between the bregma (-2.12 mm) and lambda sutures. The mice were injured at a depth of 1.25 mm, velocity of 3 m/sec, and a delay time of 100 msec. At 1, 7, 14, 30, 60, 90, and 120 d after injury, the animals were perfused intra-cardiac with 0.9% saline followed by 10% phosphate-buffered formalin. The whole brain was removed, sliced, and stained for microglial (Iba1) and astrocyte (GFAP) activation. The brains from aged (12 and 18 mo) mild TBI animals were assessed at the 30 d time-point only. Results: Here, we found that in the young animals (3 mo old), compared to noninjured controls, the activation pattern of microglia (p < 0.01, d 14 and 30) and astrocytes (p < 0.001, d 30 and 60) in the cortex (in close proximity to the injury zone) was significantly increased during the acute and sub-acute time-points. In contrast, the aged (12 and 18 mo old animals) did not exhibit an increase in activated glia on day 30 after trauma. Conclusions: Glia activation in the brain persists during both the acute and chronic phases and the aged animals exhibited a different microglia activation profile compared to the young animals, which may explain the differences in outcomes in these groups.
P06. HISTONE DEACETYLASE 4 (HDAC4) EXPRESSION ELEVATED IN MOUSE SKELETAL MUSCLE AFTER BURN Juquan Song, Melody Saeman, Steven Wolf, University of Texas Southwestern Medical Center Background: Histone deacetylases 4 (HDAC4) is class II HDAC and regulates DNA transcriptional activity via removing acetyl groups from histone. Elevated serum high mobility group box-1 (HMGB1) was associated with decreased nuclear HDAC activity in an ischemia-reperfusion liver injury animal model. HDAC4 translocated into cytoplasm and decreased its activity in response to oxidative stress. Burn injury induced early HMGB1 release, which is correlated with high risk for lethality in patients. The purpose of the study is to investigate HDAC4 expression in response to burn. Hypothesis: HDAC4 decreases its activity and contributes to hyperinflammatory response after burn. Methods: C57BL6 adult mice received 25% TBSA scald burn under general anesthesia. Mice were euthanized at day 1 and 3 for gastrocnemius muscle tissue collection. Four animals without burn served as controls. Tissue protein was extracted from whole muscle tissue lysate, and examined by Western blot. Subcellular fraction of proteins in sarcoplasm and nuclear were extracted with a Fractionation Kit for Tissue (Thermo Fisher Scientific Inc., Rockford, IL). Statistical significance accepted at p < 0.05. Results: HDAC4 is expressed in both sarcoplasm and nuclei of skeletal muscle, and approximately 39.9% is expressed in the nuclear fraction. The ratio of HDAC4 to GAPDH in sarcoplasm fraction significantly increased at day 3 (1.62 – 0.15 vs. 0.98 – 0.02 in non-burn) (p < 0.01). The ratio of absorbance of HDAC4 in the nuclear fraction to sarcoplasmic fraction significantly decreased to 0.32 – 0.008 at day 3 after burn (p < 0.01, vs. 0.67 – 0.07 in non-burn). Conclusions: Severe burn stimulated HDAC4 expression in muscle tissue, which mainly accumulated in cytosolic fraction. HDAC4 translocated from the nucleus to sarcoplasm in response to injury stress, and it might exaggerate inflammation response with HMGB1 acetylation and release following burn injury.
S-25 P07. IDENTIFICATION OF THE CRITICAL ROLE OF MMP-8 IN A MURINE MODEL OF SEPSIS Michael Cripps, Steven Wolf, Joseph Minei, Deborah Carlson, University of Texas Southwestern Medical Center Background: Severely injured patients often develop complications from derangements in inflammation, coagulation, and sepsis. While these processes are considered separate entities, recent data supports mechanistic links between them. Matrix metalloproteinases (MMPs) and tissue inhibitors (TIMPs) regulate tissue remodeling associated with inflammation and have also been implicated in coagulation disturbances. Although increased MMP-8 levels have been identified in clinical studies of injury and early sepsis, its activity is poorly characterized. Hypothesis: We hypothesize that activity of a neutrophil-derived MMP (MMP-8) will be increased during sepsis. Methods: Sepsis was induced with lipopolysaccharide (LPS) injection while controls received phosphate-buffered saline. Serum and tissue samples were taken at 0, 0.5, 1, 4, 8, 18, 24, and 48 h after infection. Circulating cytokines were measured as was RNA and protein from the heart, liver, and lungs. IL-6, IL-10, TNF, IL-1, MMP [-2, -8, -9], and TIMP [-1, -2] were measured. Results: Serum MMP-2 levels were significantly depressed compared to control at 8, 24 and 48 h post-injection (149 – 9 ng/mL, 123 – 21 ng/mL, and 121 – 37 ng/mL vs. 198 – 33 ng/ml). In contrast, serum MMP-9 levels 2, 4, 8 and 24 hours rose after LPS (246 – 64 ng/ml, 219 – 74 ng/ml, 216 – 34 ng/mL and 165 – 38 ng/mL vs 84 – 26 ng/mL). Serum MMP-8 was also elevated compared to control at 8, 24 and 48 h post-LPS (79 – 8 ng/mL, 92 – 7 ng/mL and 91 – 9 ng/mL vs 65 – 7 ng/mL). TIMP-2 levels in septic mice were not elevated significantly. Cardiac MMP-2 mRNA decreased in all tissues while cardiac MMP-8 mRNA expression was significantly increased at 8, 24 and 48 h (6.3 – 1.3 normalized fold expression [NFE], 10.2 – 4.0 NFE and 6.5 – 2.5 NFE vs. 1.00 – 0.65 NFE). Cardiac TIMP-2 mRNA expression was not statistically significant. Conclusions: The alterations of MMP-2, -8, and -9 during septicemia are consistent with clinical studies. In our model of LPS-induced sepsis, both serum MMP-8 levels and tissue MMP-8 mRNA expression were significantly increased at 8, 24, and 48 h following LPS injection. Understanding the complete mechanism of MMPs can clarify the link between injury and sepsis as well as provide potential therapeutic targets.
P08. HEMIN-INDUCED ENDOTHELIAL AND ORGAN INJURY IN EXPERIMENTAL SEPSIS Paul Waltz, Jason Luciano, Solomon Ofori-Acquah, Sruti Shiva, Brian Zuckerbraun, University of Pittsburgh Introduction: Hemolysis in sepsis occurs to varying degrees and is not unique to specific pathogens. Red blood cell breakdown releases erythroid damage-associated molecular pattern molecules (eDAMPs), including heme. Cell-free hemoglobin and heme have been correlated with endothelial injury in a number of hemolysis-associated diseases. In sepsis, cell-free hemoglobin correlates with outcomes in experimental models and is a predictor of survival in human beings with severe sepsis. Hypothesis: The purpose of these experiments was to test the hypothesis that heme contributes to endothelial and organ injury in experimental sepsis. Methods: Male C57BL/6 micer underwent cecal ligation and puncture or sham surgery and were sacrificed from 6–24 h. Additionally, mice received intravenous hemin or subcutaneous tin protoporphyrin (SnPP) or cobalt protoporphyrin (CoPP), to respectively inhibit or induce heme oxygenase (HO) activity. Endpoints examined included serum measurement of heme and hemoglobin, cytokines, and measurements of organ injury. Furthermore, Western blotting for proteins involved with heme processing were measured. Primary mouse lung endothelial cells were utilized in vitro and viability and endothelial activation were determined. Statistical analysis included one-way ANOVA. Results: CLP increased cell-free hemoglobin and heme levels. The addition of hemin (oxidized heme; 10 - 75 mcg/kg) to CLP exacerbated organ injury and systemic inflammation (p < 0.05). Inhibition of HO activity with SnPP led to significantly worse injury, while pre-CLP over-expression of HO-1 using CoPP prevented hemin-induced injury. Red blood cell lysates or hemin were toxic to endothelial cells in vitro, resulting in endothelial activation and increased expression of adhesion molecules, increased endothelial cell production of reactive oxygen species and decreased rates of oxidative phosphorylation. HO-1 over-expression with CoPP or via adenoviral gene transfer limited these changes. Conclusions: The release of eDAMPs, including heme, may contribute to vascular and organ injury in sepsis. Strategies to modify this signaling pathway may prove useful as therapeutic adjuncts in sepsis.
P09. ELEVATED PLASMATIC PERCENTAGE OF IMMATURE PLATELET FRACTURE IS ASSOCIATED WITH INCREASED MORTALITY IN SEPTIC SHOCK PATIENTS Qin Wu, Jianan Ren, Medical School of Nanjing University, Nanjing, China Background: Sepsis, the systemic inflammatory response to infection, is an aggressive, multifactorial syndrome associated with high mortality in patients. Microcirculation change and coagulation disturbance are thought to play a key role in sepsis through activating coagulation factors and platelets. Some evidence suggests the usefulness of the percentage immature platelet fraction (IPF%) as a routine laboratory test and as an
S-26 inexpensive daily screening for bacterial infection in patients with neutrophilia. In a recent study, IPF% is further proved to be useful to predict the development of sepsis in the emergency department. However, no study evaluated the association between IPF% and sepsis-associated mortality until now. Hypothesis: We hypothesized that increased IPF% enables the identification of a group of septic shock patients at high risk of death. Methods: This is a prospective study conducted in a surgical critical care unit in Jinling Hospital, Nanjing, China. Consecutive patients who were diagnosed with septic shock were enrolled. Age- and gender- matched non-septic patients were recruited as control patients. IPF% was determined by flow cytometric analysis. Results: Plasmatic IPF% was measured in 68 septic shock patients after the onset of shock and 68 control patients after enrollment. IPF% was significantly lower in control patients (p = 0.004). Among septic shock patients, non-survivors presented with significantly higher IPF% compared with survivors (p < 0.001). The area under the receiver- operating characteristic curve for IPF% association with mortality was 0.867 (95% CI: 0.780–0.953, p < 0.001). Kaplan–Meier survival curves illustrated that mortality was significantly different after stratification based on IPF% (p < 0.001). This association was preserved in multivariable logistic regression analysis including clinical confounders (p = 0.014). Conclusions: This prospective study demonstrated increased IPF% enables the identification of a group of septic shock patients at high risk of death. This biomarker may be of interest for patient stratification in future clinical trials.
P10. ONCOSTATIN M RECEPTOR DEFICIENCY RESULTS IN ATTENUATED PERITONEAL INFLAMMATORY RESPONSE AND ENHANCED SURVIVAL IN A MURINE SEPSIS MODEL Saad Salim, Nour AlMalki, Rachel Khadaroo, Thomas Churchill, University of Alberta Background: Our population is rapidly aging and frail elderly patients have been shown to have increased morbidity and mortality when faced with sepsis. The immune system in the elderly is altered with functional impairments in cell-mediated and innate immunity. Oncostatin M (OSM) is a part of the IL-6 cytokine family that has been shown to have pleiotropic functions in hematopoiesis, immunologic, and inflammatory networks. There is an increase in levels of OSM in patients experiencing septic shock, although the exact mechanism of OSM in sepsis remains elusive. Hypothesis: We hypothesize that OSM receptor (OSMR) deficiency lowers the inflammatory process in sepsis in the elderly. Methods: Mice older than 55 wks were used. Wild-type (WT) littermates and OSMR knockouts (OSMR-/-) were giving intra-peritoneal injection of cecal slurry (CS), mimicking peritonitis. CS was obtained from healthy WT C57BL/6 mice and prepared to LD30 of 1.3 g of mice per mg of cecal contents. Mice were observed for 18 h while being clinically assessed on appearance, activity, response to stimuli, eyes, and respiratory rate. Subsequently, mice were euthanized and the organs were harvested. Peritoneal lavage using 3% BSA in PBS was cultured in anaerobic chambers, while serum endotoxin levels were measured. Results: None of the mice (n = 17) had died following 18 h of CS injection. However, clinical assessment showed that the WT littermates had a significantly poorer outcome than the OSMR-/- mice. Peritoneal lavage from vehicle control (5% dextrose) mice in both OSMR-/- and WT showed no culture growth in anaerobic chambers, while CS-injected OSMR-/- mice had significantly higher colony forming units (CFUs) than WT mice (305 – 22 vs. 116 – 6, respectively, p < 0.001). Conversely, OSMR-/- mice had lower serum endotoxin levels than WT (62.7 EU/mg vs. 21.1 EU/mg, respectively). Cytokine and chemokine analysis on the peritoneal lavage showed significant differences between CS injected OSMR-/- and WT mice. Conclusions: OSMR deficiency confers clinical protection in older mice. Though the OSMR-/- mice have increased bacterial survival in the peritoneum, they did not exhibit increased inflammatory processes nor did they have greater serum endotoxin levels compared to their WT littermates. We speculate that the increased survival in the OSMR-deficient mice is due to attenuated peritoneal-induced systemic inflammatory response.
POSTER PRESENTATION ABSTRACTS croscopy. The interaction between these proteins was investigated by co-immunoprecipitation. An in vitro kinase assay was performed to assess whether CaMKI directly phosphorylates and activates PINK1. Results: LPS and CCCP induced mitophagy and the translocation of PINK1, Parkin, and the autophagy protein ATG7 to mitochondria, as early as 30 min after exposure. Mitochondrial translocation of these proteins was inhibited with Ca2 + chelation. CaMKI was also recruited to mitochondria after LPS or CCCP, and both the mitochondrial recruitment and activation of p-CaMKI were Ca2 + dependent. CaMKI coimmunopreciptitated with Parkin, and CaMKI siRNA inhibited Parkin translocation to the mitochondria, suggesting that CaMKI directly regulates PINK1/Parkin-mediated mitophagy. Indeed, in an in vitro kinase assay, CaMKI directly phosphorylated and activated PINK1. Conclusions: Collectively, these findings suggest that CaMKI regulates mitophagy during sepsis by linking mitochondrial membrane depolarization to the PINK1/Parkin/ ATG7 mechanism of mitophagy. Through the regulation of PINK1/Parkin, CaMKI plays a vital role in the removal of damaged mitochondria and thereby protects the cell from a source of cytotoxic oxidant stress.
P12. NOT SO FAST: DOES TIME TO SOURCE CONTROL IMPACT SURVIVAL IN SEPTIC SHOCK? Aimee Gough, Jonathan Grotts, Jeffrey Fried, Lisa Ferrigno, Santa Barbara Cottage Hospital Background: Septic shock is associated with high mortality. Improvements in outcome have been noted with a concerted approach, as outlined in the Surviving Sepsis Campaign, which promotes goal-directed therapy including source control within a 12-h window. Source control for patients with surgical diseases is critical, but support for the suggested time interval remains poorly characterized in the literature. Hypothesis: That increased time to source control would be associated with increased mortality. Methods: This was a retrospective review of an institutional Sepsis Registry of patients who were identified prospectively and admitted to a single tertiary-care center between August 2007 and July 2013. For entry into the analysis, patients must have presented with or developed severe septic shock within 24 h of presentation and required a source control intervention. Infection source, type of intervention, and time from sepsis onset to source control were characterized and evaluated with respect to mortality. Sources of septic shock were aggregated to the following groups: Gastrointestinal (GI: perforated viscus, ischemic bowel), hepatobiliary (HB: cholangitis, cholecystitis, liver abscess), soft tissue infections (STI: necrotizing, abscess, limb gangrene, septic joint), and genitourinary (GU: pyelonephritis). Results: 113 patients met the inclusion criteria. The mean age was 62.9 y ( – 16.5), with 53 males (47%) and mean APACHE II score of 22.1 ( – 8.4). There were 20 deaths (17.7%) with GI source associated with the highest mortality (9/28 patients). Median time to source control was not significantly different between survivors and patients who expired (7.3 vs 8.4 h; p = 0.88); additionally, the mortality rate for those with source control less than 6 h (21%), 6–12 h (21%), 12–24 h (32%) or > 24 h (25%) was not different (p = 0.77). Of note, all those who were unable to receive adequate source control died. Most with GI and STI sources were controlled operatively; HB and GU sources were more often controlled via endoscopy or interventional radiology. Time to source control did not vary by method of intervention. Conclusions: While early goal-directed therapy for sepsis is thought to improve outcomes, time from the identification of sepsis to source control did not appear to have an effect on mortality in this cohort of patients with severe septic shock. Further research is required to define the optimal timing of source control for these disease processes.
P13. RISK STRATIFIED INDUCTION IMMUNOSUPPRESSION FOR ELDERLY RENAL TRANSPLANT PATIENTS IMPROVES VALUE OF CARE Corey Eymard, Winston Ally, Michelle Hurrell, Kenneth Brayman, Avinash Agarwal, University of Virginia Health System
P11. CaMKI REGULATES MITOPHAGY IN MACROPHAGES DURING SEPSIS Xianghong Zhang, Du Yuan, Emma Lee, Anthony Lewis, Brian Zuckerbraun, Matthew Rosengart, University of Pittsburgh Background: Mitochondrial dysfunction/depolarization occurs early during sepsis and serves as a significant source of cytotoxic reactive oxygen species (ROS). The removal of injured mitochondria through mitophagy is a conserved, adaptive process that mitigates this oxidant stress and thereby fosters cellular survival. Depolarization strongly induces mitophagy through a mechanism involving PINK1/Parkin, though the link between depolarization and PINK1/Parkin remains to be identified. Mitochondria serve as high-capacitance buffers of cytosolic calcium (Ca2 + ), and mitochondrial depolarization induces a leakage of buffered Ca2 + . Furthermore, our data demonstrate that CaMKIa regulates autophagy in response to sepsis. Hypothesis: CaMKI regulates mitophagy during sepsis. Methods: RAW 264.7 macrophage cells were treated with either LPS (100 ng/mL) or CCCP (10 mcM), the later of which depolarizes the mitochondrial membrane potential (MMP). CaMKI activity was modulated with the biochemical inhibitor STO609 or transfection of CaMKI siRNA. Intracellular Ca2 + was chelated with BAPTA. The translocation of PINK1, Parkin, ATG7, p-CaMKI and total CaMKI to mitochondria was determined by immunoblot of isolated mitochondria or immunofluorescence cell mi-
Background: There is limited literature on immunosuppression optimization in the elderly transplant population ( ‡ 65 y), although there was a 40% increase in renal transplantation in this population over the last decade. This study aims to evaluate graft rejection, infectious complications, and 30-d readmissions after implementation of a risk-stratified immunosuppression protocol. Hypothesis: Using risk stratification to guide induction immunosuppression in the elderly does not increase graft rejection and decreases infectious complications. Methods: This is a retrospective cohort study of elderly patients who underwent transplantation from 2011 to 2014 at an academic center where immunosuppression was guided by historic (HT) or risk-stratified (RS) protocols. Risk stratification was based on immunologic risk (sensitization, age, and graft function) with rabbit antithymocyte globulin (ATG) dosing ranging from 1.5–3 mg/kg of adjusted weight in RS cohort verses 4.5–6 mg/ kg in HT. Graft survival, acute rejection, infectious complications and 30-d re-admissions were evaluated. Univariate analysis was performed. p < 0.05 was considered significant. Results: 23 patients met study criteria: 6 in HT and 17 in RS. Demographics and acute rejection were similar at 3 and 6 mo (HT: 17% vs. 19% and HT: 33% vs. 19%; p = ns) between cohorts. CDC-defined infections were less common in RS as compared to HT, with 1.19 (RS) and 1.50 (HT) infections per patient at 6 mo and 0.3 (RS) and 0.67 (HT) infections at 12 mo (p = ns). 66.7% patients in HT and 37.5% in RS experienced UTI at 6 mo, with 50% (HT) and 0% (RS) experiencing UTI at 12 mo (p = ns). At 6 and 12 mo, there were similar rates of BK viremia (HT: 16% vs. RS: 12.5% and 0% vs.
POSTER PRESENTATION ABSTRACTS 6.25%, respectively, p = ns), CMV viremia (HT: 16.6% vs. RS: 18.8% and 0% vs. 0%, p = ns), bacteremia (HT: 0% vs. RS: 18.8% and 0% vs. 12.5% p = ns), and pneumonia (HT: 0% vs. RS: 6.25% and 0% vs. 6.25%, p = ns.). 1 case of BK nephropathy was identified at 6 mo in RS. There were no cases of invasive CMV, fungemia, or thrush. The 30-d readmission rate decreased from 66.7% (HT) to 31% (RS) (p = 0.17). The mean study follow up was 34 – 3 mo in HT and 15 – 8 mo in RS. Conclusions: These data demonstrate that immunosuppression by risk stratification in the elderly maintains excellent clinical outcomes with low rejection and infection rates. These data also emphasize the need for effective immune monitoring to allow for further individualized immunosuppression to improve quality.
P14. BENEFIT OF TEAMSTEPPS ROUNDING IMPROVEMENT PROJECT ON INFECTION-RELATED MONITORING Jack C He, Joseph Golob, Jr., Kate Clancy, David Schechtman, Jeffrey Claridge, Case Western Reserve University, MetroHealth Medical Center Background: TeamSTEPPS was developed to improve teamwork and patient safety, and was shown to benefit patient care in complex clinical settings including intensive care units. Our 2 trauma/surgical ICUs received TeamSTEPPS training, but only Unit 1 participated in a TeamSTEPPS Rounding Improvement Project (TRIP). Our goal was to assess any unintended benefit to infection-related monitoring and prevention from TRIP. Hypothesis: TRIP implementation in ICUs would be associated with better monitoring, resulting in improved antibiotic and invasive line/tube stewardship. Methods: Between September and November 2014, trained observers collected data prospectively on rounds in both units. Unit personnel were blinded to the data collection process. Monitoring variables obtained for each patient encounter include: Review of invasive line/tube presence (endotracheal tube, central line, and urinary catheter), and review of antibiotic indication and course. For patients on antibiotic and had invasive line/tube, we conducted a retrospective review for treatment variables such as: Antibiotic duration and cessation accuracy, inappropriate antibiotics days (time difference between actual and planned stop date), and invasive line/tube duration. Results: 416 patient encounters were observed. The use of invasive line/tube was reviewed on rounds significantly more in Unit 1 than Unit 2 (83% vs. 51%, p < 0.005). In the 135 encounters with patients on antibiotics, review of antibiotic indication, stop date, day into course, and all 3 components occurred significantly more in Unit 1. Based on the 65 different antibiotic courses encompassed by the 135 encounters, antibiotic duration, cessation accuracy, and inappropriate antibiotic days were not significantly different between units. From the same 135 encounters, 125 had invasive line/tube placement. Significantly more discussion of line/tube presence occurred in Unit 1, but the duration of their presence was not significantly different (Table 1). Conclusions: TRIP was associated with an unintended, increased monitoring of antibiotics and invasive line/tube usage. Nevertheless, this did not translate into significant, immediate treatment differences.
P15. PERCUTANEOUS DRAINAGE RATES AFTER CHOLECYSTECTOMY ARE HIGHER IN PATIENTS WITH GALLSTONE DISEASE VERSUS MALIGNANCY Jonathan P. Meizoso, Laura Teisch, Xiomara Ruiz, Gerardo Guarch, Mena Hanna, Casey Allen, Juliet Ray, Carl Schulman, Kenneth Proctor, Danny Sleeman, Nicholas Namias, University of Miami Miller School of Medicine
S-27 Background: The rate of intra-abdominal collections (IAC), including abscess and biloma, after cholecystectomy is low. To our knowledge, a direct comparison of IAC rates after cholecystectomies performed for gallstone disease (GS) vs. gallbladder/ hepatocellular (biliary) cancer (CA) has not been performed. Hypothesis: We hypothesize that the rate of percutaneous drainage after cholecystectomy is higher in patients with GS vs. biliary CA. Methods: A retrospective review of all cholecystectomies from 2009–2014 was performed. To properly identify all patients requiring percutaneous drainage (PD), only patients who had an additional procedure within a 1-y period after their cholecystectomy were included. Operations requiring intestinal anastomoses (e.g., Whipple procedure) and patients with abdominal trauma were excluded due to potential contamination with intestinal contents. Demographics, operative technique, prior abdominal surgery, and need for percutaneous drainage were assessed. Chi-square or Fisher exact tests were used for categorical variables, as appropriate. Student t-test was used for continuous variables. Significance was set at alpha = 0.05. Results: 3,369 cholecystectomies were performed during the study period. 343 patients met inclusion criteria. Demographics were: age 50 – 15 y, 69% female, 49% Hispanic, 29% white, 20% black, BMI 29 – 6 kg/m2. Overall need for PD was 18%. Indication for cholecystectomy was GS in 86% and CA in 15%. Laparoscopic surgery (76% vs. 6%, p < 0.001), intraoperative cholangiography (24% vs. 6%, p = 0.006), female gender (71% vs. 57%, p = 0.05), previous abdominal surgery (45% vs. 21%, p = 0.003), post-operative antibiotic usage (52% vs. 18%) & BMI (29 – 6 vs. 26 – 5, p = 0.002) were significantly higher in the GS group. Need for post-operative CT scan (44% vs. 27%, p = 0.017), age (58 – 13 vs 49 – 15 y, p < 0.001), operative time (265 – 139 min vs. 151 – 73 min, p < 0.001), & need for PD (42% vs. 14%, p < 0.001) were significantly higher in the CA group. Conclusions: Although cholecystectomies for GS disease are frequently performed for infectious etiologies (e.g., acute cholecystitis), cholecystectomies performed for biliary malignancy required percutaneous drainage more frequently. This difference might be secondary to the immunodeficiency and malnutrition that are often associated with malignancy. Surgeons should investigate for the presence of IAC in the appropriate clinical scenario. Further prospective studies are required to identify predictors of the need for PD after cholecystectomy.
P16. CHLORHEXIDINE PROPHYLAXIS FOR PREVENTION OF VENTILATOR-ASSOCIATED PNEUMONIA IN TRAUMA AND SURGICAL INTENSIVE CARE UNITS Matthew Kesinger, Juan Carlos Puyana, Melissa Duque, Jason Sperry, University of Pittsburgh Background: Ventilator-associated pneumonia (VAP) is an important cause of morbidity and mortality in intensive care units (ICUs) ranging between 15% and 41%. Mortality in this population may exceed 50%, and recent evidence suggests that ICU patients who develop VAP have an increased risk of worse functional and neurological outcomes. Chlorhexidine (CX) decontamination of the oropharynx may decrease the incidence of VAP. Previous systematic reviews and meta-analyses investigating CX oropharynx decontamination have either combined medical and surgical ICU patients, or have investigated special populations such as cardiac surgery patients. No metaanalysis has investigated the potential effects of CX in decreasing VAP specifically in trauma and surgical ICUs. Hypothesis: CHX decreases VAP and mortality in trauma and surgical ICUs. Methods: MEDLINE, PubMed, clinical trial registries and Google were searched for randomized controlled trials (RCT) of CX prophylaxis vs. either placebo or standard treatment for VAP in mechanically ventilated patients treated in a general surgical or trauma ICU. Studies were excluded that investigated CX vs. another experimental intervention. Results: We identified 278 results. 253 records were excluded and 25 full-text records were assessed for eligibility. We included 4 studies published between 2004 and 2011 and one study completed in 2013 with reported results but that has not been published. The population totaled 337 patients. The quality of evidence was moderate. Patients receiving CX prophylaxis were one-half as likely to contract VAP compared to placebo or standard of care (RR 0.52, 95%CI 0.32-0.83, p = 0.006). However, there were insufficient outcomes reported to determine the effect of CX in this population as regards mortality.
S-28 Conclusions: Evidence suggests that the use of CX for decontamination of the oropharynx in mechanically ventilated patients treated in trauma/surgical ICUs decreases the incidence of VAP. However, the quality of evidence is moderate and the quantity is low. The evidence is less clear regarding the effect of CX on mortality, length of mechanical ventilation, and length of ICU stay in this patient population.
P17. EFFECT OF PERSISTENT THROMBOCYTOPENIA ON MORTALITY IN SURGICAL CRITICAL CARE PATIENTS: A RETROSPECTIVE STUDY Qin Wu, Jianan Ren, Medical College of Nanjing University, Nanjing, China Background: Thrombocytopenia is a common laboratory abnormality in surgical critically ill patients. Most previous research in critical care-related thrombocytopenia was focused on the association between the occurrence of thrombocytopenia and mortality. Still, there is little study to evaluate the impact of duration of thrombocytopenia in surgical critical care patient population on mortality. Hypothesis: We hypothesised that persistent thrombocytopenia is a clinically significant event and is associated with worse outcomes as compared with transient thrombocytopenia. Methods: This was a retrospective 12-mo cohort study of adults consecutively admitted to a surgical intensive care unit. Patients were identified from a prospective critical care database, and thrombocytopenia events were diagnosed. We defined persistent thrombocytopenic patients as those who experienced thrombocytopenia for more than 7 consecutive days during the same episode. Patients who had experienced persistent thrombocytopenia were defined as Group A. The other would be ascribed to Group B. The primary endpoint was hospital inpatient mortality. Results: Of 536 patients, 32 experienced persistent thrombocytopenia and 55 experienced non-persistent thrombocytopenia. Patients in group A and group B had similar demographics, comorbidities, and inpatient clinical factors. Mortality in Group A was significantly higher than that in Group B. as well as in ICU and hospital stay. Traditional risk factors failed to predict differences between patients with or without persistent thrombocytopenia. Conclusions: Thrombocytopenia is common among critically ill surgical patients. Persistent thrombocytopenia is a clinically significant event and is associated with worse outcomes.
P18. DEDICATING PRE-EXISTING CENTRAL VENOUS CATHETERS FOR PARENTERAL NUTRITION: ARE ROUTINE SURVEILLANCE BLOOD CULTURES NECESSARY? Sandra Marie Swoboda, Patricia Brown, David Efron, Lindsay Stander, Pamela Lipsett, The Johns Hopkins Medical Institutions Background: Routine surveillance blood cultures are used to dedicate pre-existing catheters for parenteral nutrition as a standard of care at our institution. The most recent guidelines state that ‘‘catheter cultures should not be obtained routinely,’’ yet long-term indwelling lines in patients who have been managed out of hospital or at another institution may be at higher risk, especially if the line is to be dedicated for nutrition administration. Hypothesis: Routine surveillance cultures are not required prior to dedicating a preexisting catheter for parenteral nutrition (CPN). Methods: This was a retrospective database review of patients from 2006–2014 with pre-existing central venous catheters that were dedicated for parenteral nutrition. Surveillance blood cultures were taken from the lumen of the catheter per protocol. Risk factors for infection included line type, number of lumens, presence of fistula, ostomy, abscess, surgical vs. medical patient, reason for use of catheter prior to parenteral dedication, WBC and Tmax. Descriptive statistics were used. Results: Overall, 92/852 patients had a positive blood culture ( + CX) (10.7%). Medicine patients (60/349) were significantly more likely to have + CX vs. surgical patients (15% vs. 7%, OR 2.22, 95% CI 1.4-3.6). The majority of catheters were PICC followed by Mediport and Hickman Catheters (HC) with HC having the highest infection rate (HC 15% vs. PICC 9% and Mediport 8%, p = 0.02). The majority of cultures were gram = positive (61%) followed by gram-negative (23%), yeast (10%) and multiorganisms (6%). Risk factors such as chemotherapy, home CPN, fistulas, ostomy, intraabdominal abscesses, or fever were not significant (p > 0.25).The mean Tmax for + CX was 37.3C. The mean WBC for + CX was 7.9 ( – 5.5) compared to 9.1 ( – 5.5) for negative cultures (p = 0.05). The regression model showed that medical patients without a history of cancer were more likely to have a positive blood culture. Conclusions: The overall rate of positive blood cultures was 10.7%. ‘‘General’’ risk factors in patients for suspicion of infection (fever, leukocytosis, fistula, cancer, surgery, type of line) are not predictive of positive blood cultures in this patient population. Routine surveillance cultures should continue as standard practice for dedication for parenteral use.
P19. ARE SCREENING NASAL SWABS TO DETECT MRSA CLINICALLY USEFUL IN PREDICTING OUTCOMES IN ADULT BURN CENTERS: A LARGE REGIONAL BURN CENTER’S EXPERIENCE Shawn Tejiram, Laura Johnson, Brittany Hamilton, Kimberly Johnson, Jenny Zhang, Lauren Moffatt, Jeffrey Shupp, Firefighters’ Burn and Surgical Research Laboratory, MedStar Health Research Institute
POSTER PRESENTATION ABSTRACTS Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a nosocomial pathogen known to be present in wounds, leading to delayed wound healing, scar formation, sepsis, and even death. The incidence of community-acquired MRSA has risen over the past decade. This has prompted swab-based nasal screening on admission to identify asymptomatic carriers. Hypothesis: The aim of this study was to determine if screening nasal swabs for MRSA upon admission to a major urban burn center would affect outcomes or patient management. Methods: A retrospective review was conducted on all burn-injured patients who presented to a regional burn center between June 1, 2012 and June 30, 2014. Hospital electronic medical records and scanned charts were reviewed for patient demographics, clinical management, and bacterial culture testing. Patients who did not have a nasal swab or bacterial wound culture within 48 h of admission were excluded. Identified MRSA positive patients were then subcategorized as early or late based on organism identification less than 48 h after admission or afterward, respectively. Length of stay analysis was then done after normalizing to percent total body surface area burn (% TBSA). Results: 799 patients met initial criteria. In this population, 54 (6.7%) patients screened positive for MRSA during their hospital course. Patients who stayed greater than 48 h had a length of stay of 4.64 d per % TBSA. Of these, 30 patients were identified with early MRSA compared to 21 patients with late MRSA diagnoses. The mean length of stay was 3.53 d in early MRSA patients compared to 6.09 d in late MRSA patients; this was not statistically significant. Conclusions: Burn-injured patients who stay in the hospital greater than 48 h and are diagnosed with MRSA at any point in their hospital stay have longer lengths of stay than published norms in the burn population (1 day per 1% TBSA). The early identification of patients who are colonized with MRSA might allow for modifications in their treatment and surgery in order to improve their outcomes. More work is underway to identify causal relationships between colonization and infectious complications.
P20. CUMULATIVE EFFECT OVER TIME OF IMPLEMENTATION OF AN EARLY MOBILITY PROTOCOL ON DEVELOPMENT OF PRESSURE ULCERS Sheryl Kwak, Kathleen To, Sharon Dickinson, University of Michigan Background: Pressure ulcer development remains a significant quality issue in critically ill patients. We recently implemented an early mobility protocol in the surgical ICU. This study aims to determine the impact of our protocol on pressure ulcer development by comparing the changes in pressure ulcer rates during the early and late phases of our protocol implementation. Hypothesis: We hypothesized that familiarity with the early mobility protocol would lead to increased pressure ulcer-free days (PUFD) in the late group. Methods: The early mobility protocol was initiated in late 2010 in the surgical ICU of an academic tertiary care center as part of an ongoing quality initiative. This protocol consists of three phases where the patients progress from passive range of motion to dangling at bedside then to walking with the bedside nurse starting day 1 in the ICU. Data on patient characteristics and pressure ulcer development were collected prospectively for all patients admitted to the surgical ICU. Data collected between October 2010 and June 2011 (early implementation group) were compared to data collected between January and September 2014 (late implementation group). Each hospital visit was recorded as a separate encounter. A pressure ulcer-free day was defined as a hospital day during which an onset of a new pressure ulcer did not occur. Results: In the early implementation group, a total of 523 ICU visits were recorded, for a total of 4,145 ICU days. Of these, 87 visits had documented new PU development (16.7%). Average ICU length of stay (LOS) for patients without pressure ulcers was 4.9 d vs. 22.8 d in patients with pressure ulcers. In the late implementation group, a total of 809 ICU visits were recorded for a total of 4,443 ICU days. Of these, 74 visits had new documented PU ulcer development (9.2%). Average ICU length of stay (LOS) for patients without pressure ulcers was 4 vs. 18 d in patients with pressure ulcers. In the late implementation group the average number of pressure ulcer-free days was 14.60 vs.12.95 in early implementation group. Conclusions: This study suggests that familiarity with an early mobility protocol has increased the number of pressure ulcer-free days and may also decrease the incidence of pressure ulcers.
P21. AN AUDIT AND FEEDBACK PROGRAM CAN DECREASE WOUND CLASSIFICATION ERRORS Sydne Muratore, Stacy Carda, Jill Thurston, Alyssia Mills-Hokanson, Mary Kwaan, University of Minnesota Background: Accurate wound classification is an important component of surgical site infection (SSI) risk-adjustment models. At our institution, protocols direct the circulating nurse to finalize and record wound class in the electronic health record after a ‘‘debrief’’ process with the surgeon, however the accuracy of this process is unknown. Hypothesis: Periodic audit of wound classification, with feedback to individual surgeons and systems interventions, can increase wound classification accuracy. Methods: A prospective wound classification audit and feedback project was performed through the NSQIP program for all cases at an academic hospital. Audit: Each month, adult cases from all specialties performed during a 7-d time frame were reviewed. Procedure title and wound classification assignment were reviewed for potential discrepancies. Endoscopic procedures, with the exception of percutaneous endoscopic
POSTER PRESENTATION ABSTRACTS
gastrostomy procedures, were excluded. Feedback: When a discrepancy was detected, the surgeon champion sent a notification to the operating surgeon with review of CDC wound classification definitions. Study end point: Monthly discrepancy rates were assessed with the one-sided Cochran-Armitage Trend Test. Feedback interventions concluded when the discrepancy rate reached a nadir. Results: Over 13 mo, 3,104 cases were reviewed (mean 239 (SD 26) cases/mo). The wound classification discrepancy rate was 8.1% at the start of the project and 1.9% at the conclusion of the project, with 159 discrepancies in total. Inappropriate classification of bowel and genitourinary cases as class I instead of class II accounted for 62% of cases. Under-classification of contaminated or dirty cases (class III/IV) accounted for 38% of cases. Of the 175 class III/IV cases performed during the audit, 34% were misclassified. A clear decrease in the rate was not seen until after 7 mo. Overall, a decrease in discrepancies was seen (p = 0.037; Figure), however 3 mo after feedback stopped, the rate increased slightly (p = 0.16). Conclusions: An audit/feedback system can increase surgeon attention on the wound classification of cases, however improvement is slow and may require ongoing feedback in order to be sustained.
P22. PHYTOBEZOARS AND SMALL BOWEL OBSTRUCTION: THE CASE OF THE GRAPE ILEUS Anna Liveris, Michael Zeidman, Peter Kim, Albert Einstein College of Medicine, Jacobi Medical Center Background: Small bowel obstruction is a substantial health and economic burden, accounting for more than 300,000 hospitalizations, 30,000 deaths, and $3 billion per year in the United States. The etiologies of SBO can be broadly classified into extraluminal and intraluminal causes. Extraluminal causes are far more common, with postoperative adhesions alone accounting for about 75% of cases. Intraluminal obstruction is usually caused by a primary tumor, although obturators such as gallstones, foreign bodies, and bezoars have been reported. Phytobezoars, bezoars containing vegetable matter, are rare culprits that account for only 0.4%–4% of all SBO. Hypothesis: We present a case of SBO caused by a grape phytobezoar. Methods: An 83 y-o female with past medical history of diabetes, congestive heart failure, and dementia presented with severe acute abdominal pain, nausea, and unrelenting emesis. She had no past surgical history. She was tachycardic to 121 beats/min. She was an anxious-appearing, elderly obese demented lady oriented only to person and place. She had one single tooth with poor dentition. Her abdominal exam was notable for diffuse tenderness to palpation with rebound and guarding but no palpable masses or hernias. Her labs included a WBC of 14.2 and lactate of 1.95. A portable abdominal x-ray showed multiple dilated loops of small bowel. By CT scan, a soft tissue density was seen within the lumen of the distal small bowel. Results: Given the patient’s worsening peritonitis, the patient underwent emergent exploratory laparotomy. Upon inspection, a palpable endoluminal mass, approximately 2x3 cm in size, 5 cm from the ileocecal valve, caused a volvulus and gangrene of small bowel with closed-loop obstruction. An ileo-cecetomy with side-to-side stapled anastomosis was performed. The specimen contained a 3-cm intact grape with multiple raisins more proximal. The abdomen was irrigated and closed. She was discharged on POD 12 in stable condition. Conclusions: This is the third reported case of SBO caused by an intact grape.
P23. BACTEROIDES FRAGILIS BACTEREMIA IN THE SURGICAL POPULATION: A 7-YEAR REVIEW AT A LARGE TERTIARY CARE CENTER Albert Hsu, Casey Allen, Jonathan Meizoso, Juliet Ray, Carl Schulman, Kenneth Proctor, Nicholas Namias, University of Miami Miller School of Medicine
S-29 Background: Bacteroides fragilis is the most common anaerobic organism causing bacteremia in human beings. However, the clinical significance of a positive B. fragilis blood culture in guiding surgical management remains undetermined. Hypothesis: To determine if B. fragilis bacteremia is indicative of need for urgent operative or radiologic drainage. Methods: This is a retrospective study of all patients with a positive B. fragilis blood culture admitted to a major tertiary care center from January 2007 to December 2013. Patient records were reviewed to determine if there was a potential surgical source for the anaerobic bacteremia defined as the presence of any intra-abdominal or soft tissue infection that may require an operative or radiologically guided percutaneous intervention. Results: 82 patients had a positive B. fragilis blood culture. 38 patients (46%) had a non-surgical source: age 61 (53–73) y, 47% male, LOS 10 (6–22) d, and mortality of 24%. 44 patients (54%) had a potential surgical source: age 53 (48–61) y, 57% male, LOS 19 (12–54) d, and mortality of 23%. 24 patients required urgent drainage of an intra-abdominal infection; 17 patients required operative drainage and 7 patients required radiologically-guided percutaneous drainage. Time to operative intervention was 2.5 – 4.0 d and time to percutaneous drainage was 2.7 – 3.1 d. Nine of the 17 patients requiring operative intervention had the procedure performed on the same day as the positive culture. Mortality was 29% in patients requiring operative drainage and 14% in patients requiring percutaneous drainage. Three patients had developed sepsis and multisystem organ failure from an intra-abdominal infection, however did not undergo any intervention; all died. Three patients had an intra-abdominal infection not associated with sepsis that was treated only with antibiotics; all survived. Four patients had a soft tissue infection that was treated with debridement or amputation. Overall, 32 of 44 patients (73%) with a potential surgical source for a positive B. fragilis blood culture had indications for an operative or radiologically guided percutaneous intervention. Conclusions: A positive B. fragilis blood culture is highly suggestive of the need for an infection source control procedure. This knowledge may confirm clinical suspicion and help guide recognition and treatment of surgical patients with an intra-abdominal or soft tissue infection.
P24. INTRAPERITONEAL SULFATED POLYSACCHARIDE INCREASES THE RISK OF PERITONITIS IN THE PRESENCE OF CONTAMINATION Alex Charboneau, John Delaney, Kristine Mulier, Gregory Beilman, University of Minnesota Background: Several sulfated polysaccharides are used clinically. Some competitively bind selectins that are essential for neutrophil rolling and tissue infiltration. This may suppress innate immunity. Prior work investigating fucoidan, a sulfated polysaccharide, for abdominal adhesion prevention led to an apparent increased incidence of peritonitis. Hypothesis: Intraperitoneal fucoidan increases the risk of developing bacterial peritonitis. Methods: Part i: An adhesion model was created in rats. A 2.5X2.5 cm full-thickness midline abdominal wall section was excised. The skin was re-approximated with a primary closure. An osmotic pump was implanted subcutaneously, and an IP catheter was attached for 7-d continuous delivery. Control animals (n = 11) received water. Treatment animals (n = 14) received dissolved fucoidan (7 mg/d). Animals were sacrificed on day 7 and abdominal cultures were taken. Part II: In a separate experiment, control rats (n = 9) received an IP injection of Staphylococcus aureus in PBS and no operation. Treated rats received the same dose of S. aureus and received fucoidan delivered from a subcutaneous pump (n = 3, 7 mg/d). Before sacrifice on day 7, body temperature and blood samples were acquired. Peritoneal cultures were performed. Results: Part I: Treatment animals had a significantly greater incidence of positive culture with associated peritonitis ( p = 0.001). Isolated species were Streptococcus agalactiae, S. aureus (MSSA), and Proteus mirabilis. Part II: Animals that received IP bacteria alone had no sign of infection at sacrifice. Abdominal cultures were negative. All animals that received fucoidan had peritonitis and positive abdominal cultures (S. aureus) at 7 d. Mean body temperature and WBC count were significantly greater in treatment animals (p < 0.05). Conclusions: IP fucoidan increases the rate of bacterial peritonitis compared to control animals in this model. This is potentially due to innate immune suppression and contamination. Control rats are able to defeat large doses of bacteria. The addition of fucoidan allows these bacteria to persist. These data suggest that fucoidan may inhibit the ability to fight contamination occurring during or after operations.
P25. MAPPING THE ZINC (ZN) MANAGEMENT NETWORK IN RAW 264.7 MACROPHAGES (MF) IN THE RESPONSE TO E. COLI BACTERIAL ENDOTOXIN (LPS) David Soybel, Samina Alam, Aneeqa Syed, Jonathan E. Kohler, Amy B. Baver, Brett E. Phillips, Shannon L. Kelleher, Penn State Hershey College of Medicine Background: Intracellular availability of Zn is critical for signature activities of the Mø in its response to injury or infection. Cellular Zn management is regulated by a network of Zn transporters: ZIP proteins (ZIP1-14) that mediate Zn movement into the cytoplasm
S-30 from outside the cell or from other organelles and ZnT proteins (ZnT1-10) that transfer Zn out of the cytoplasm to the outside or into intracellular compartments. Hypothesis: Exposure to danger signals such as LPS drives a transformation of the Zn management network in the monocyte, supporting its polarization to an activated macrophage. Methods: Mouse-derived RAW 264.7 cells were monitored under control conditions and after 16 h exposure to purified LPS (100 nM). Select Zn transporters were attenuated by siRNA-mediated transfection. Measurements included a) 65Zn uptake and efflux; b) response of intracellular Zn levels ([Zn]i) to extracellular Zn loads (50 mcM for 1 h), using real-time microscopy and the Zn-sensitive reporter, FluoZin-3; c) changes in Zn transporter protein expression; and d) sub-cellular localization using confocal imaging and cell surface biotinylation. Results: Exposure to LPS did not affect 65Zn uptake into RAW cells but did increase efflux compared to that observed in untreated cells (0.19 – 0.01 vs. 0.13 – 0.01 pmol Zn/mcg protein, p < 0.05). In response to extracellular loading, accumulation of Zn increased significantly ([Zn]i 4.9 – 0.3 nM vs. 2.3 – 0.3 nM, p < 0.01). Consistent with internal redistributions of Zn, > 2-fold changes in protein abundance were observed in response to LPS for several ZIPs (2, 7 decreased; 3, 4, 6, 10, 12, 13, 14 increased) and for Zn transporters that vesicularize Zn (2, 3, 4, 8, all increased). Cell surface biotinylation and efflux studies with siRNA indicate that LPS-stimulated 65Zn efflux is mediated by ZnT8-containing vesicles at the cell surface. Conclusions: Coupled with recent studies of ZIP and ZnT localization in diverse cell types, these findings provide a comprehensive working model for Zn management in the LPS-stimulated RAW 264.7 cell. Our observations suggest that Zn accumulation into vesicles and the cytoplasm may participate in regulating signature functions of the Mø and provide novel evidence that it secretes Zn to the extracellular space, an activity that is enhanced by exposure to LPS. This observation offers the possibility that the macrophage may interact with its environment and neighboring cells through secretion of Zn as an extracellular signal.
P26. ADVANCING THE DEVELOPMENT OF A STAPHYLOCOCCUS AUREUS VACCINE TO PREVENT POSTOPERATIVE INVASIVE S. AUREUS DISEASE BY TARGETING MULTIPLE BACTERIAL VIRULENCE FACTORS Ingrid L. Scully, James Baber, Paul Liberator, David Cooper, Edward Zito, Joseph Eiden, William Gruber, Emilio Emini, Kathrin Jansen, Alejandra Gurtman, Annaliesa Anderson, Pfizer Vaccine Research Background: The gram-positive organism Staphylococcus aureus is responsible for serious postoperative infections, including deep tissue and blood stream infections. Risk of infection is dependent on multiple patient factors, including age and comorbidities, as well as numerous procedural factors such as duration and complexity of surgery. There is currently no licensed vaccine to meet this critical unmet medical need. Hypothesis: We present a strategy for developing an effective vaccine for the prevention of invasive S. aureus disease by eliciting immune responses targeting important S. aureus virulence factors. Methods: The vaccine candidate was assessed pre = clinically using in vivo models of surgical site infection and disseminated disease, and by the development of in vitro immunoassays that measure relevant functional vaccine responses from both pre-clinical studies and clinical subjects (clinical studies B2251002 (NCT01018641) and B3451001 (NCT01364571)). Results: A S. aureus 4-antigen vaccine (SA4Ag), consisting of capsular polysaccharides type 5 and type 8 conjugated to CRM197, and recombinant forms of two S. aureus surface proteins, clumping factor A (ClfA) and manganese transporter C (MntC) was developed. Selection of the antigens was based on addressing important virulence mechanisms as well as early in vivo expression and efficacy in preclinical animal models. In Phase 1/2 clinical trials, a single administration of an investigational 3-antigen or 4-antigen vaccine exhibited an acceptable safety profile and elicited a functional antibody response in a high proportion of subjects. Conclusions: The preclinical and early clinical results support the planned testing of SA4Ag in human efficacy studies. In addition, the rapid induction of functional antibodies after a single dose provides a window of opportunity to vaccinate prior to elective surgery. This represents an important step forward in developing a vaccine to prevent postoperative invasive S. aureus disease.
P27. TIME OF ONSET OF BACTERIAL VERSUS FUNGAL INFECTIOUS COMPLICATIONS IN SEVERE ACUTE PANCREATITIS Zil Patel, Emily Heil, Surbhi Leekha, Brandon Bruns, Jose Diaz Jr. University of Maryland, R. Adams Cowley Shock Trauma Center Background: Infectious complications are a leading cause of mortality in severe acute pancreatitis (SAP). While bacterial infections are the most commonly encountered, fungal infections are becoming increasingly recognized in this population. There are limited data regarding the use of antifungal prophylaxis in the management of patients with SAP and routine use is controversial. Hypothesis: The purpose of our study was to identify average time of onset for fungal infections compared to bacterial infections in patients with SAP with the hypothesis that onset will be significantly longer for fungal. Methods: A retrospective study was performed on a prospectively collected singlecenter Acute Care Surgery registry from 2010 to 2013. Inclusion criteria were patients age > 18 y, with SAP, and an infectious complication defined by a positive bacterial or
POSTER PRESENTATION ABSTRACTS
fungal culture from peritoneal fluid, abscess, or blood. All other sites of infection were excluded. Time to onset of infection was defined as time between the date of admission and the date of first positive culture result. Patients with cultures positive for both bacteria and fungus contributed data twice, separately for time to first positive bacterial and first positive fungal culture. The median time to onset of bacterial and fungal infection was compared using nonparametric tests. Results: Of 394 patients with SAP, 70 patients (18%) developed an infectious complication. Of these, 15 patients had both bacterial and fungal infection. All fungal infections were with Candida spp. Sixty-five first episodes of bacterial infection were compared with 20 episodes of first positive fungal infection. The median time to fungal infection 18 d (inter-quartile range (IQR) 4-40) compared to 10 d (IQR 1-17) for bacterial infections. The time to onset of fungal compared to bacterial infection was significantly longer (Figure, p = 0.03). Conclusions: In a cohort of patients with SAP and associated infectious complications, time to onset of fungal infection was significantly longer than bacterial infection. This information can help contribute to future studies of timing of antifungal prophylaxis and empiric treatment in the SAP population.
P28. CLOSTRIDIUM DIFFICILE INFECTION IN HOSPITALIZED TRAUMA PATIENTS: ANALYSIS OF EPIDEMIOLOGY AND RISK FACTORS Karen Obermann, Thomas Schroeppel, John Sharpe, L. Clement, Louis Jude Magnotti, Jordan Weinberg, Timothy Fabian, Martin Croce, University of Tennessee Health Sciences Center Background: Clostridium difficile infection (CDI) is a potentially virulent and increasingly prevalent problem. Incidence varies by reporting method and patient population, ranging from 0.79% to 21%. Prophylactic (orthopedic and maxillofacial injuries) and therapeutic antibiotics are common in trauma patients. While antibiotic pressure is a known risk factor for CDI, a paucity of literature exists about the epidemiology of this disease in this population. Hypothesis: We hypothesize that antibiotic stewardship with strict adherence to algorithms and de-escalation will limit the incidence of CDI. We sought to determine the incidence and associated factors for CDI. Methods: A retrospective case-control study was conducted on patients admitted from October 1, 2006 to September 30, 2013. Patients who died or were discharged within 72 h of admission were excluded. Aggressive screening in hospitalized patients with diarrhea was routine. Cases of CDI were identified from an institutional registry and diagnosed by toxin assay or PCR. Control patients treated during the same time period were matched 2:1 with cases by Injury Severity Score (ISS) and age. Demographics, antibiotic usage, and infection data were evaluated. Antibiotic stewardship including, monitoring of prophylaxis, de-escalation following cultures, and strict adherence to a pneumonia algorithm with diagnosis by quantitative cultures ( > 105 cfu/mL) were followed during the study period. Results: 116 cases of CDI were diagnosed in 16,488 admissions over the 96-mo period for an incidence of 0.7% and an incidence rate of 0.61/1,000 patient-days. The mean age was 46 y with the majority male (68%) and mechanism blunt trauma (88%). Univariate analysis demonstrated that patients who developed CDI had a more severe brain injury (GCS 10 vs. 12; p = 0.008), received more transfusions (10 vs. 5 units; p = 0.001), and received more antibiotics (13 vs. 9 d; p = 0.003). There was no difference in mortality, but ICU (26 vs. 13 d; p < 0.001) and hospital LOS (42 vs. 18 d; p < 0.001) were longer by 13 and 24 d in CDI, respectively. Stepwise multivariable logistic regression identified pneumonia (OR 5.8; 95%CI 3.4–10.1) and transfusions (OR 1.03; 95%CI 1.00–1.06) as independent predictors of CDI. Conclusions: CDI is increasing in frequency and severity across the country. Management algorithms and antibiotic stewardship limits exposure to unnecessary antibiotics. Adhering to these principles led to the low incidence rate of 0.61/1,000 patient days.
POSTER PRESENTATION ABSTRACTS P29. DIFFERENTIAL EFFECT OF ENTEROCOCCUS FAECALIS GELATINASE (GELE) AND SERINE PROTEASE (SPRE) ON COLONIC EPITHELIAL CELLS MORPHOTYPE SWITCHING TO A MESENCHYMAL-LIKE PHENOTYPE: ROLE IN ANASTOMOTIC LEAK Natalia Belogortseva, Kristina Guyton, Baddr Shakhsheer, Olga Zaborina, John Alverdy, University of Chicago Background: Myofibroblasts make up the intestinal extracellular matrix and thus its healing properties and originate from epithelial cells that acquire a mesenchymal phenotype (epithelial-mesenchymal transition, EMT). Macrophage-derived matrix metalloprotease (MMP-9) is known to promote EMT. Previous work from our lab demonstrated that intestinal E. faecalis can activate MMP-9 in a GelE/SprE-dependent manner and cause anastomotic leak. Hypothesis: Here we hypothesized a role for E. faecalis GelE/SprE in promoting the EMT process through macrophage activation and disruption of epithelial cells tight junctions. Methods: E. faecalis V583, its derivative mutant deficient in the gelE/sprE operon (DDgelEsprE), and its complemented mutant on a multiple-copy plasmid (DDgelEsprE/ gelEsprE) were used in this study. Macrophages J774 were incubated with the various bacterial strains for 5 h, the conditioned medium was collected and sterilized, and then applied onto two types of intestinal cells: Normal intestinal epithelial cells YAMC (young adult mouse colonic epithelium) or C57BL/6 mouse primary colonic epithelial cells. After 16 h of incubation, epithelial cells were examined for phenotype changes using phase-contrast microscopy and for epithelial markers by immunofluorescence staining and Western blot analysis using E-cadherin and ZO-1antibodies. Results: Conditioned media from macrophages co-incubated with the wild type GelE/SprE-producing strain V583 induced a striking phenotypic change in both epithelial cell lines to the mesenchymal-like phenotype whereas the GelE/SprE deficient strain DDgelEsprE did not. Complementation of the deficient mutant with gelE/sprE (DDgelEsprE/gelEsprE) restored the strain to its transformational phenotype. Transformed cells demonstrate a spindle-shaped morphology, and some cells had a flat polygonal shape with multiple branches. Western blot showed reduction of E-cadherin in transformed cell lysates. Immunofluorescence showed a striking decrease in E-cadherin and the tight junction protein ZO-1 whose localization was changed in transformed cells. Conclusions: Intestinal E. faecalis expressing GelE/SprE, via its interaction with macrophages, may influence epithelial cells to acquire a mesenchymal phenotype and thus influence the structure and function of the extracellular matrix and potentially healing.
P30. THE FREQUENCY AND SUSCEPTIBILITY OF MULTI-DRUGRESISTANT GRAM-NEGATIVE ISOLATES FROM INTRA-ABDOMINAL INFECTIONS IN THE UNITED STATES, 2012–2013 Sam Bouchillon, Robert Badal, Meredith Hackel, Sibylle Lob, Aaron Johnson, International Health Management Associates, Inc. Background: The treatment of patients with intra-abdominal infections (IAI) is complicated by the presence of increasing numbers of multi-drug-resistant (MDR) pathogens. The SMART program has monitored in vitro activity of several antimicrobial agents commonly used in IAI since 2002. Hypothesis: Knowledge of the current frequency and in vitro susceptibility of MDR isolates from the United States is helpful in the clinical treatment of IAI. Methods: From 2012 to 2013, 21 US centers collected 3,209 aerobic gram-negative IAI clinical isolates. Of these, 254 were determined to be MDR, defined as resistance to 3 or more CLSI drug classes. Isolates were identified to species level and sent to a central lab for confirmation of identification and susceptibility testing. MICs were determined using broth microdilution panels according to CLSI guidelines. Results: 7.9% of the IAI isolates tested were MDR. MDR n, Total n, %MDR, frequency, and % susceptible of the comparators against 254 MDR isolates are shown in the table. Conclusions: Only amikacin, ertapenem, and imipenem-cilastatin were effective ( > 90% susceptible) against MDR strains of Escherichia coli, the most frequently isolated IAI pathogen. Amikacin was effective against 13 of 18 MDR species, more than any other study drug. No study drug was effective against the second and third most
AK, amikacin; CAZ, ceftazidime; CEP, cefepime; CTX, cefotaxime; FOX, cefoxitin; ETP, ertapenem; IMP, imipenem-cilastatin; LVX, levofloxacin; P/T, piperacillin-tazobactam.; NA – BPs not defined. Susceptibilities > 90% are highlighted.
S-31 common MDR species from IAI, Klebsiella pneumoniae and Pseudomonas aeruginosa. Although the susceptibility to amikacin approached 80% against P. aeruginosa, all drugs inhibited < 65% of MDR K. pneumoniae at their respective CLSI breakpoints.
P31. INCIDENCE AND RISK FACTORS FOR CLOSTRIDIUM DIFFICILE INFECTION IN THE PEDIATRIC SURGERY POPULATION Simone Langness, Radhames Lizardo, Katherine Davenport, Julia Grabowski, University of California, San Diego, Rady Children’s Hospital Background: In the pediatric population, infection with Clostridium difficile is uncommon, but can significantly impact morbidity and mortality. Manifestation of the disease is typically restricted to self-limited diarrhea, making diagnosis challenging as diarrhea is present in a myriad of other pediatric diseases. In the surgical population, additional risk factors for C. difficile infection include the standard use of perioperative antibiotics, increased incidence of proton pump inhibitor (PPI) use and the need for gastrointestinal surgery. In general, the incidence of C. difficile infection in the pediatric population is not well known and even less is known with respect to incidence, risk factors, and outcomes in the pediatric surgery patient. Hypothesis: We hypothesize the additional risk factors for C. difficile infection incurred in the pediatric surgery population will result in a higher incidence of infection in this population compared to the general pediatric population. Methods: A retrospective review was conducted on all patients at a free-standing children’s hospital with positive C. difficile stool toxin assay between 7/2013-10/2015. Data were collected on demographics, C. difficile risk factors including recent antibiotic use, prior hospitalizations, PPI use, immunosuppression and inflammatory bowel disease, and outcomes. Surgical patients (S) were defined as C. difficile infection occurring within 30 d postoperatively. Results: C. difficile toxin assay was performed on 948 patients during the study period with 82 (8.6%) positive. Of the positive cases, 13 (16%) occurred within S group. The most common surgical procedures performed were establishment of vascular access (n = 4), followed by cardiac surgery (n = 3) and general surgery (n = 3). General surgery cases included appendectomy, diagnostic laparoscopy, and ileocecectomy in a patient with ulcerative colitis. 10 (77%) of S patients had at least one major risk factor for C. difficile (antibiotics > 3 d, immunosuppression, or IBD) and all had at least one comorbidity. Conclusions: The incidence of C. difficile is the pediatric surgery population is low and major risk factors for the infection are present in the majority of cases. Stool toxin assays remain a facile and inexpensive test to diagnose C. difficile infection, however, the low pretest probability may limit its utility in patients with minimal risk factors.
P32. SIGNIFICANCE OF MICROPERFORATION IN PEDIATRIC APPENDICITIS Simone Langness, Radhames Lizardo, Katherine Davenport, Julia Grabowski, University of California, San Diego, Rady Children’s Hospital Background: Appendicitis is the most common pediatric surgical emergency, and treatment often varies based on the presence or absence of an appendiceal perforation. While the majority of perforations are diagnosed intraoperatively based on gross appearance, a subset is discovered on pathologic review. The pathologic diagnosis of microperforation is defined as inflammatory exudate extending to the serosa or periappendiceal fat, noticeable only on microscopic exam. The significance of this discovery is unknown at this time and may influence the duration of antibiotic therapy for children with this finding. Hypothesis: We hypothesize that length of stay and readmission rates will be higher in pediatric patients with a pathologic finding of microperforation compared to patients with non-perforated appendicitis. Methods: We performed a retrospective review of appendectomies performed from 1/2011 to 1/2013 in our university practice and identified those whose pathology revealed microperforation. We reviewed demographic data, intraoperative findings, and pathology reports. Outcomes in these patients were compared to outcomes from patients with uncomplicated and complicated appendicitis (perforated or with abscess). Treatment was at the surgeon’s discretion in accordance with institutional algorithms, including IV antibiotics until afebrile for 24 h. Patients with complicated appendicitis received an additional 5-d course of oral antibiotics after discharge. Results: There were 2,393 appendectomies performed during this 24-mo period. 200 patients were identified with a pathologic finding of appendiceal microperforation. Among patients with microperforation, there were an equal number treated as uncomplicated and complicated. Of those patients with microperforation that were treated as uncomplicated, readmission rate was 9.0% compared to 7.0% for those who were treated as complicated. The overall readmission rate of patients with uncomplicated and complicated appendicitis without microperforation was 1.9% and 5.6% respectively. For patients with microperforation, 89% of infection-related readmission occurred in patients treated as uncomplicated. Conclusions: When patients with microperforation are treated as uncomplicated appendicitis, they have a higher rate of readmission than in those treated as complicated appendicitis. Specifically, infection-related readmission is considerably higher. A modification of the treatment protocol for patients in which microperforation is found on pathology should be considered.
S-32 P33. DOCTOR, SOMETHING’S MOVING UNDER MY SKIN. CASE REPORT AND REVIEW OF FURUNCULOID DERMATOBIA HOMINIS MYIASIS Federico Grasa Gonza´lez, Lotfi Elmalaki Hossain, David Sa´nchez Relinque, Sistema Andaluz De Salud, Hospital Punta De Europa Background: Myiasis is the infestation of organs and tissues, by vertebrates dipteros, usually flies. Myiasis furunculoid cases described in Spain are imported, since none of the species that produce myasis live in Spain. Most common species are Dermatobia hominis, imported from Latin America; and Cordylobia anthropophaga, corresponding to cases imported from Africa. Methods: Case report and literature review. Results: A 35 y-o male background stayed in Bolivia for 2 mo on a humanitarian mission, returning 4 wk ago. He has been mmunized against yellow fever, typhoid fever, and hepatitis A. He presented to the Emergency Department with two vesiculo-pustular left shoulder lesions and a right axillary abscess 2.5 cm that did not respond to antibiotic therapy. He referring to a feeling that there was ‘‘something moving under my skin.’’ Drainage of the pustular lesions yielded 2 barrel-shaped larvae with dark hooks in the cephalic part and several rows of spines surrounding the body, identified as D. hominis larvae. The adult female fly acts as a temporary host by capturing other biting flies (mainly mosquitoes of the genus Psorophora). Eggs are deposited on her abdomen that are fixed in place (phoresis). The eggs hatch and penetrate the host, causing an injury with a hole in its center through which the larva breathes. Larvae pupate, with emergence of an adult fly in 20–60 d completing their life cycle in 3–5 mo. Conclusions: Man is an accidental host. Skin lesions consist of subcutaneous nodules isolated or grouped, that are migratory, erythematous, painful (especially to pressure), and in some cases pruritic and can produce agitation and insomnia in the host, in addition to the sensation of movement under the skin. The treatment of cutaneous lesions involves removal of larvae under local anesthesia.
POSTER PRESENTATION ABSTRACTS preceded the meningitis and appeared to be the cause of the meningitis that led ultimately to death. The burn team should be vigilant in cases involving burns of the face when resistant Pseudomonas is prevalent. Early ophthalmologic support and additional therapies including intra-vitreous treatments and intrathecal antibiotic installation may be options.
P35. ROLL OUT OF A UNIVERSAL PRE-OPERATIVE DECONTAMINATION THERAPY PROTOCOL FOR PATIENTS UNDERGOING ELECTIVE SURGERY Celia N Robinson, Carla Braxton, Samir Awad, Baylor College of Medicine Background: Surgical site infections (SSI) are the second most common type of hospital acquired infection (HAI) and in most cases are preventable. SSIs commonly caused by MRSA carry significant morbidity and mortality. Previously, we demonstrated a significant reduction in SSI rates in orthopedic surgery patients after the implementation of a preoperative decontamination program that consisted of intra-nasal antiseptic ointment and chlorhexidine (CHG) washcloths. Hypothesis: Our objective is to describe our process for the implementation of a universal decontamination project across selected surgical services in a tertiary care center. Methods: The implementation of the decontamination project included formation of a team including the chief of surgery, infection control, pre-operative and surgical clinic directors, and a LEAN methodology facilitator. A process map of the protocol to determine how the project could be implemented within the workflow of general, vascular, orthopedic, and neurosurgery services was created. Education was provided to preoperative and surgical front-line clinical staff. Instruction sheets and decontamination packets consisting of the intra-nasal antiseptic ointment and CHG washcloths and oral rinse were distributed to the pre-operative clinics. Simulation was performed, which included preoperative testing of MRSA carrier status, patient education about the decolonization protocol, and distribution of the decontamination packets. Patients returned an instruction sheet with stickers from the CHG washcloths indicating compliance with the intervention. Results: After implementation, there were no meaningful changes made to the process. From October 1, 2014 to December 1, 2014, approximately 141 patients participated in the decontamination protocol. To date, 50% (n = 71) have undergone surgery. The compliance rate of patients undergoing surgery was 85%. Conclusions: Through a collaborative effort, a surgical decontamination therapy protocol can be successfully implemented in a tertiary-care center across multiple surgical services. Future study is warranted to determine the continued impact on SSI rates as well as determine possible factors that increase compliance.
P36. AN EVIDENCE-BASED CLINICAL PRACTICE GUIDELINE ADAPTATION PROCESS ON SURGICAL SITE INFECTION PREVENTION Ergie Inocian, Mohammed Atallah, Yasser Sami, King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia
P34. RESISTANT PSEUDOMONAL ENDOPHTHALMITIS IN A BURN PATIENT Linwood Haith Jr., Sergio Perez, Mary Lou Patton, Robert Guilday, Nathan Speare, Crozer Chester Medical Center, Regional Burn Treatment Center Background: This case involved an 18 y-o female who sustained a 68% total body surface area flame burn in a house fire. Bronchoscopy revealed a severe upper airway injury. She underwent multiple excision and grafting procedures on post-burn days (PBD) 2, 4, and 10, and on PBD 11, excision and temporary closure of facial wounds. Additional excision and grafting procedures were performed on PBD 17 and 19. Early nutritional supplementation with tube feedings was commenced and advanced to goal as tolerated. On PBD 13 wound cultures revealed a resistant Pseudomonas sensitive to only aminoglycosides and colistin. On PBD 20 the patient developed edema, erythema, and proptosis of the right eye that was evaluated by ophthalmology. Methods: Case report and literature review. Results: Medial and lateral right canthotomies were performed. Other treatment modalities including intra-vitreous antibiotics were discussed, but not performed. CT of the brain at that time showed concern for retrobulbar inflammation. There was progressive decrease in her mental status. On the day before death she was noted to have left nystagmus. An additional brain CT scan showed diffuse cerebral abnormalities and edema. Neurologic exam at that time showed absent cerebral activity consistent with brain death, which was confirmed by repeat neurologic exam. Post-mortem exam revealed meningitis as the cause of death and also right endophthalmitis. Conclusions: Only 2 previous case reports of endophthalmitis associated with burns have been reported: Snow et al. (1992) and Jain and Garg (1995). In this case it appears that the endophthalmitis was precipitated by the periorbital anitibiotic-resistant pseudomonal infection and perhaps a previous periorbital procedure. The endophthalmitis
Background: The issue of surgical site infection (SSI) prevention is one of the high priority health topics for clinical practice guideline (CPG) production in the nursing department due to the following reasons: 1) prevalence of the condition in KKUH; 2) the burden associated with SSI; 3) concerns about practice variation; 4) the likelihood that the CPG will be effective in influencing practice; 5) the potential for improving quality of care or patient outcomes; and 6) the existence of relevant good-quality evidencebased CPGs in the international context. Because a rigorous process of CPG development is costly and time-consuming, the hospital has relied on adaptation of guidelines developed internationally by experts. Methods: The description of the methodology for the production of CPGs in the hospital utilized the sequential process for trans-contextual adaptation of CPGs proposed by the ADAPTE working group of the Guidelines International Network (G-I-N). The ADAPTE Manual and Resource Toolkit Version 2.0 was used as a guide in the adaptation process. Results: The panel retrieved 27 source CPGs; 24 CPGs were excluded based on the identified selection criteria, and 3 were considered for further assessment. The National Guidelines Clearinghouse (NGC) ‘‘Compare Guidelines’’ tool was used to compare the 3 selected CPGs. The Appraisal of Guidelines Research & Evaluation II (AGREE II) Instrument was used to assess the quality of the CPG. The overall assessment and decision of the panel was to adapt the CPG from the NICE [London, UK], 2008 Oct., reaffirmed 2011). Conclusions: SSI prevention is a high-priority health topic for CPG development, adaptation, and implementation both locally and internationally. The ADAPTE process for CPG adaptation (v. 1.0 and 2.0) is an rigorous scientific process for clinical performance improvement, which can be adapted further according to the local context.
P37. DIABETIC FOOT INFECTIONS: SYSTEMATIC REVIEW OF BACTERIAL PREVALENCE Federico Grasa Gonza´lez, David Sa´nchez Relinque, Lotfi Elmalaki Hossain, Sistema Andaluz De Salud, Hospital Punta De Europa
POSTER PRESENTATION ABSTRACTS
S-33 earlier diagnosis of SSI and minimize emergency room visits and preventable readmissions. Future work will include analysis of clinical outcomes at 30 d post-discharge.
P39. PREOPERATIVE ETAPENEM RESTRICTION FOR EMERGENT EXPLORATORY LAPAROTOMY DEMONSTRATES COST SAVINGS BUT DOES NOT ADVERSELY AFFECT SURGICAL SITE INFECTION RATE William Peppard, David Eberle, David Milia, Sara Revolinski, John Weigelt, Medical College of Wisconsin
Background: Foot infections are a common reason for hospitalization and a cause of complications in patients with diabetes. The aim of this study was to determine the prevalence of microorganisms found on culture in complicated diabetic foot infections (DFI) in hospitalized patients (Lipsky. PEDIS grade 3–4, IDSA 2004). Methods: Between January 2012 and December 2014, 52 samples from 79 diabetic patients with moderate/severe infection were collected for microbiologic study prior to surgery. Results: At least one microorganism was isolated in 75% of samples. Most frequently isolated were gram-positive bacteria (75%), most often Staphylococcus aureus (40%); followed by Pseudomonas aeruginosa (15%), Enterococcus spp. (15%), and Escherichia coli (5%). Among the multi-drug-resistant microorganisms, MRSA was most common (20% of the isolated S. aureus), followed by E. coli resistant to amoxicillinclavulanic acid and ciprofloxacin (Figure). Conclusions: Gram-positive cocci predominate for superficial and mild infections, whereas in deeper and severe infections, polymicrobial flora are characteristic with gram-positive cocci, gram-negative bacilli and anaerobes. Anaerobic bacteria are prevalent in the presence of ischemia or necrosis and generally as part of mixed infections. The specific susceptibilities for different microorganisms in each healthcare environment is of great importance in the choice of antibiotic treatment, especially when osteomyelitis is demonstrated. Our empiric treatment approach was based on the severity of infection: Oral amoxicillin-clavulanic acid for minor infection, ertapenem for moderate-to-severe infections, and the other carbapenems, piperacillin-tazobactam and linezolid reserved for the most serious infections, when it is appropriate to cover P. aeruginosa and MRSA.
P38. PATIENT-REPORTED WOUND SYMPTOMS AND PATIENT-PROVIDER AGREEMENT ON SSI Timo Hakkarainen, Patrick Sanger, Cheryl Armstrong, Andrea Hartzler, Heather Evans, University of Washington and GroupHealth Research Institute Background: Surgical site infections (SSIs) are a common and costly post-operative problem, contributing to substantial morbidity, mortality, and increased cost of care. Because post-operative stays have shortened, most SSIs now manifest after hospital discharge. Hypothesis: While patients may report symptoms consistent with SSI, patient assessment of symptoms will be of limited use in diagnosing SSIs. Methods: We conducted a prospective pilot observational study of post-operative patients surveyed for wound symptoms at time of discharge, 3-d post-discharge (PD), at post-operative clinic follow-up (POCV), and at 30-d PD. At POCV, care providers were surveyed on signs of SSI, as well as the diagnosis of SSI. Patients were considered to have SSIs who were diagnosed by their surgical team, had their incision opened, had positive cultures, or were provided antibiotics by their surgical team. Results: Between 23 and 28 patients completed surveys at the various time points. 57% of patients reported at least one symptom at time of discharge, 46% and 48% reported symptoms at 3-d and follow-up visit respectively, and 36% reported symptoms at 30-d post-discharge. Concordance between patient and provider assessments on signs and symptoms ranged from 57%–100% (mean 83%) The two patient-reported symptoms found among those with provider-diagnosed SSI were wound discharge and separation, with one patient reporting each. Three patients self-reported having a SSI. Two patients were diagnosed by providers as having SSIs. Overall concordance about the presence or absence of SSI at POCV was 79%, but PPV of patients self-diagnosing SSI was 33%, and the inter-rater agreement between providers and patients when patients thought they had an SSI was very low (k = 0.125). Conclusions: There was significant discrepancy between patient and provider diagnosis of SSI, and no specific symptoms, or combination of symptoms accurately diagnosed SSI. The high gross correlation observed represented patients and provider agreement when no signs and symptoms or no SSI was present. Correlation between patient-diagnosed wound problems and provider assessment was no better than chance, and this highlights the need for better tools to enable objective assessment of wound healing by the surgical team, in addition to patient-reported symptoms, in order to allow
Background: Current recommendations for perioperative antibiotic (abx) use for emergent laparotomy after penetrating abdominal injury include abx options with short and long half-lives. We recently substituted two short-acting options, cefoxitin (cfx) and ampicillin/sulbactam (a/s), for a long-acting drug, ertapenem (ert). Owing to their short half-lives, intraoperative re-dosing with a/s and cfx is necessary for procedures exceeding 2 h whereas ert does not require re-dosing. This study characterizes the incidence of surgical site infection (SSI) following the removal of ert as a perioperative choice. Hypothesis: The substitution of a short-acting abx for a long-acting abx for emergent exploratory laparotomy (ex-lap) perioperative prophylaxis does not adversely affect incidence of SSI, and will result in cost savings. Methods: A retrospective chart review was performed on patients who underwent an ex-lap within 24 h of admission in 2013. The primary outcome was SSI defined by CDC criteria within 30 d of the initial ex-lap. Patients with SSI were compared to those without; as well as those who received a short-acting antibiotic or a long-acting antibiotic (a/s or cfx) or a long-acting antibiotic (ert, moxifloxacin, ciprofloxacin, clindamycin, cefazolin + metronidazole). Results: A total of 149 patients were included: 85% male, mean age of 32.7 y. Mean time from emergency department to incision was 99 min; 65 (43.6%) had bowel penetration. Short-acting abx was given in 88 of 151 (58.3%); only 7 patients (4.7%) received ert. SSI was identified in 12/149 (8%) patients including superficial (2), deep (1), and organ/space (9); of these patients 9 (75%) had bowel penetration. There was no difference in SSI between groups. Based on surgery duration, 21/149 (14.1%) had an indication for intra-operative abx re-dosing, though most did not receive (18/21, 85.7%) an intraoperative dose. Of these 21 patients, 20 received short-acting pre-operative abx of which only one developed a SSI. The reduction in ert use resulted in an estimated $56,000 savings when compared to use prior to pathway removal. Conclusions: Intraoperative dosing of short-acting perioperative abx was indicated but omitted in the majority of patients, although no increase in SSI rates was observed. An economic benefit accrued using short-acting abx, but further investigation, possibly using risk stratification, is needed to define the optimal use of these less expensive shortacting abx.
P40. IMPROVEMENT OF INFLAMMATORY RISK MARKERS IN DIABETIC FOOT INFECTION WITH ERTAPENEM Lotfi Elmalaki, Federico Grasa Gonza´lez, David Sa´nchez Relinque, Sistema Andaluz De Salud, Hospital Punta De Europa Background: Diabetic foot infections (DFIs) are associated with substantial morbidity and mortality. Important risk factors for development of diabetic foot infections include neuropathy, peripheral vascular disease, and poor glycemic control. Diabetic foot ulcers are a major cause of morbidity, accounting for approximately two-thirds of all nontraumatic amputations performed in the United States and 60% in Spain. Up to 85% of cases are triggered by an ulcer associated with infection and gangrene. Amputations are becoming more frequent, while the quality of life after amputation is greatly reduced. Hypothesis: The aim of this observational study was to establish the efficacy of ertapenem treatment in DFI, as well as the behavior of inflammatory markers with the treatment. Methods: Systematic review, retrospective and observational between the years 2012–2014, to assess the rate and incidence of DFI in the Health Area of Campo de Gibraltar (AGSCG) in Ca´diz, Spain, and to determine the incidence of major and minor amputations, and the improvement of the evolution of the cases with ertapenem. Results: With a total number of 79 patients studied (overall mean age 69.04 y, average age males 64.3 y, and females 73.4 y). At admission the Wagner classification scale was Grade 1: 2.9%; Grade 2: 10.5%; Grade 3: 22.8%; Grade 4: 59.6%). Significant elevation of inflammatory markers was observed among fibrinogen, procalcitonin, and leukocyte/lymphocyte counts. Income patient without surgical treatment (antibiotics) was 19.25%. Overall days total income: 9.5 d. Conclusions: Treatment with ertapenem was observed effective, reducing acute phase reactants of these patients. In patients with a high Wagner score and poor outcome they stated surgical treatment associated with antibiotic treatment. A good percentage of patients did not require major amputations with the therapy applied.
P41. INFECTIOUS COMPLICATIONS AFTER OPEN, DEPRESSED SKULL FRACTURES DO NOT VARY WITH CHOICE OF ANTIBIOTIC PROPHYLAXIS REGIMEN Helen Harvey, David Shellington, Susan Duthie, Ruth Bush, Bradley Peterson, Christopher Cannavino, Mary Hilfiker, Johns Hopkins University and University of California, San Diego, Rady Children’s Hospital
S-34 Background: Limited data exist to guide administration of antibiotics after open, depressed skull fractures in children. Treatment protocols are extrapolated from adult data. The purpose of this study was to investigate the type and duration of antibiotic(s) administered and the frequency of infection after these injuries in children. Hypothesis: We hypothesized that empiric antibiotic administration would reduce infectious complications after open, depressed skull fractures. Methods: We performed an IRB-approved, retrospective review of patients admitted over a 4-y period who were identified from a prospectively generated trauma registry. Patients were included if they were aged < 15 y and had an open, depressed skull fracture. Data collected included demographic variables, duration and type of antibiotic(s) administered, and type of infectious complication (meningitis or abscess). Results: Thirty patients met inclusion criteria. The average age of the cohort was 7.7 – 2.5 y with 21 (70%) males. Patients received antibiotics for an average of 10.5 – 1.6 d after injury. The most common antibiotics were cefazolin (57%) and vancomycin + meropenem (37%). Seven (23%) wound cultures were obtained with 2 showing bacterial growth (6%); one for Bacillus sp. and one for Staphylococcus epidermidis. Only one patient (3%) developed a clinical infection after injury (epidural abscess). Duration of antibiotics significantly correlated with maximum temperature (r = 0.51, p < 0.003). Patients with contamination of the intracranial space via sinus involvement, dural tear, or cerebrospinal fluid leak were treated with longer courses of antibiotics than those without these injuries (16.0 – 4.6 vs. 6.8 – 1.0 d; p < 0.05). Conclusions: Infectious complications after open, depressed skull fracture were uncommon in this pediatric cohort. Longer courses of antibiotics were administered to patients with evidence of CSF contamination without discernable reduction of incidence of infection or benefit between choices of antibiotics due to the low incidence.
P42. DOES IT REALLY MATTER? PROPHYLACTIC ANTIBIOTICS AND INFECTION IN PENETRATING BRAIN INJURY Tara Paterson, Daniel Haase, Amit Anand, Joseph Kufera, Manjari Joshi, Thomas Scalea, Deborah Stein, University of Maryland Medical Center, R. Adams Cowley Shock Trauma Center Background: Penetrating brain injury (PBI) traditionally carries a very high mortality. In survivors, hospital course can be complicated by central nervous system (CNS) infections. There are no current guidelines for prophylactic antibiotic (PBX) administration in PBI. This study investigated infection rates in those who received PBX vs. those who did not. Hypothesis: PBX decreases CNS infection in PBI. Methods: A retrospective chart review was performed between 2006 and 2011 on patients with PBI, defined as CT evidence of dural penetration. The PBX group included all patients receiving antibiotics (ABX). The infected group included patients with > 24 h length of stay (LOS) and those who received ABX for CNS infection based on physician decision, positive CSF, or cultures. The primary outcome was overall rate of CNS infection. Secondary outcomes were type of infection, LOS, and mortality. p < 0.05 was statistically significant. Results: There were 307 PBI patients identified. Overall mortality in PBI was 63%, the majority of whom died within 24 h. Eighty-two (27%) patients received PBX. Of the 122 (40%) patients who survived to intensive care unit (ICU) admission, 53 (43%) received PBX. Fifty-three (43%) of ICU admissions received PBX vs. 29 (16%) of nonICU patients (p < 0.001). Overall CNS infection rate was 3% (n = 8). These included 5 meningitis, 2 ventriculitis, and 1 SSI. Of the ICU survivors receiving PBX, 6 (7%) developed CNS infections. Only 2 (1%) in the no PBX group developed CNS infections, indicating significant difference in infection rates between PBX and no PBX groups (p = 0.005). Seven patients developed CNS infection and survived to discharge. Only 1 patient died with CNS infection. There was a significant difference (p < 0.001) between those who received PBX and survived (n = 70, 61%) and those who received PBX and died (n = 12, 6%). Median LOS for the PBX group was significantly longer than the LOS of those who did not receive PBX (6.0 vs. 0.1 d, p < 0.001). Conclusions: The overall CNS infection rate in PBI was 3%, which is consistent with existing data. The majority of the patients identified as having PBI did not receive prophylaxis, although a higher proportion of ICU admissions received prophylaxis. Our
POSTER PRESENTATION ABSTRACTS study indicates that the prophylaxis group admitted to ICU had a higher infection rate. This finding is possibly explained on the basis of the severity of PBI. In this subgroup, the role of PBX for prevention of CNS infections needs further evaluation.
P43. EVIDENCE-BASED VALUE OF SURGICAL WOUND DRAINAGE IN THE PREVENTION OF SURGICAL SITE INFECTION: A META-ANALYSIS AND SYSTEMATIC REVIEW Xiuwen Wu, Jianan Ren, Gefei Wang, Jieshou Li, Medical School of Nanjing University, Nanjing, China Background: The widespread utilization of post-operative drains has been questioned due to concerns regarding both efficacy and safety, particularly with respect to the risk of surgical site infection (SSI). Hypothesis: The purpose of this study was to determine the evidence-based value of prophylactic drainage of surgical wounds in the prevention of SSI. Methods: An electronic search was performed. Articles reporting incidence of SSI with prophylactic drainage in postoperative wounds were identified and classified by level of evidence. If sufficient randomized controlled trials were included, a metaanalysis was performed using the random-effects model. Fifty-three randomized controlled trials were included in the meta-analysis, and subgroups were determined by specific surgical procedures or characteristics (abdominal wound, mastectomy, axillary lymph node dissection, hip and knee arthroplasty, and flap reconstruction). Primary outcome was the incidence of SSI. Secondary outcomes were mortality and economic cost due to SSI. Results: Fifty-three studies with a total of 8451 operations were identified as suitable for this analysis. There were 4,713 operations in the drain group and 3,738 in the no-drain group. Prophylactic drainage did not offer a statistically significant advantage for the prevention of SSI in surgical wounds (p = 0.66), nor did it in all other procedures studied (p > 0.05). No death or economic cost due to SSI was reported in included studies. Conclusions: The evidence to suggest that drain use is associated with increased risk of SSI is weak. However, prophylactic placement of drains did not provide an advantage for prevention of SSI in abdominal wounds, mastectomy, axillary lymph node dissection, hip and knee arthroplasty, and flap reconstruction. Judicious use and prompt, timely removal is recommended when considering drain placement.
P44. FULMINANT NECROTIZING FASCIITIS AND SEPSIS FROM AEROMONAS HYDROPHILA AND A. VERONII BIOVAR SOBRIA AFTER TRAUMATIC INJURY Javier Perez, Saraswati Dayal, Brian Van Ness, Hackensack University Medical Center Background: Aeromonas hydrophila and A. veronii biovar sobria are gram-negative, motile, facultative anaerobic bacilli that morphologically resemble Enterobacteriaceae. These organisms are typically found in water sources and can cause a range of infections from minor skin infections, gastroenteritis, and more unusually severe infections such as necrotizing fasciitis, septic shock, and pneumonia. Sporadic cases of severe A. hydrophila infection associated with trauma have been reported. However, necrotizing fasciitis with sepsis due to combined A. hydrophila and A. veronii biovar sobria in the setting of trauma has not been described. Aeromonas infection with septic shock has a reported mortality of 40–80%. Hypothesis: Case report and review of literature. Methods: Case report and review of literature. Results and Conclusions: A case report of a patient who sustained multiple trauma after being struck by a street sweeper dispensing non-potable water with combined infection by A. hydrophila and A. veronii biovar sobria resulted in necrotizing fasciitis, septic shock, and aspiration pneumonia with ARDS. This case illustrates the necessary aggressive surgical treatment of Aeromonas species infection.