The Pediatric Infectious Disease Journal • Volume 33, Number 9, September 2014
Cies and Chopra
ACKNOWLEDGMENTS The authors wish to thank Dr. Stephen Druhan of the Department of Radiology of Nationwide Children’s Hospital for his assistance in reviewing the cardiac MRI. REFERENCES 1. Schutze GE, Jacobs RF. Bartonella species (cat-scratch disease). In: Long SS, Pickering LK, Prober CG, eds. Principles and Practice of Pediatric Infectious Diseases. 4th ed. Philadelphia: Elsevier; 2012:856–861. 2. Spach DH, Kaplan SL. Microbiology, epidemiology, clinical manifestations, and diagnosis of cat scratch disease. In: Rose BD, ed. UpToDate. Waltham: UpToDate; 2013. 3. Holmberg M, Wesslen E, Hjelm C, et al. Bartonella spp. in a 60 year-old Swedish male with myocarditis who succumbed to sudden death [Abstract 31]. In: Program and abstracts of the 13th Sesquiannual Meeting of the American Society for Rickettsiology. Champion, PA. September 21–24, 1997. 4. Meininger GR, Nadasdy T, Hruban RH, et al. Chronic active myocarditis following acute Bartonella henselae infection (cat scratch disease). Am J Surg Pathol. 2001;25:1211–1214. 5. Wesslen L, Ehrenborg C, Holmberg M, et al. Subacute Bartonella infection in Swedish orienteers succumbing to sudden unexpected cardiac death or having malignant arrhythmias. Scand J Infect Dis. 2001;33: 429–438. 6. Pipili C, Katsogridakis K, Cholongitas E. Mycocarditis due to Bartonella henselae. South Med J. 2008;101:1186. 7. Skouri HN, Dec W, Friedrich MG, et al. Non-invasive imaging in myocarditis. J Am Coll Cardiol. 2006;48:2085–2093. 8. Kobayashi D, Aggarwal S, Kheiwa A, et al. Myopericarditis in children: elevated troponin I level does not predict outcome. Pediatr Cardiol. 2012;33:1040–1045. 9. Holmes AH, Greenough TC, Balady GJ, et al. Bartonella henselae endocarditis in an immunocompetent adult. Clin Infect Dis. 1995;21: 1004–1007.
PROCALCITONIN USE IN A PEDIATRIC INTENSIVE CARE UNIT Jeffrey J. Cies, PharmD, MPH, BCPS-AQ ID,*†‡ and Arun Chopra, MD§¶ Abstract: We evaluated whether procalcitonin (PCT) might aid diagnosing serious bacterial infections in a general pediatric intensive care unit population. Two-hundred and one patients accounted for 332 PCT samples. A PCT ≥1.45 ng/mL had a positive predictive value of 30%, a negative predictive value of 93% and a sensitivity of 72% and a specificity of 75%. These data suggest PCT can assist in identifying patients without serious bacterial infections and limit antimicrobial use. Key Words: procalcitonin, critical care, pediatric Accepted for publication April 4, 2014. From the *St. Christopher’s Hospital for Children, Philadelphia, PA; †Drexel University College of Medicine, Philadelphia, PA; ‡Alfred I duPont Hospital for Children, Wilmington, DE; §NYU Langone Medical Center, New York, NY; and ¶NYU School of Medicine, New York, NY. This work, in part, was presented as an abstract at the 22nd Annual Pediatric Pharmacy Advocacy Group Meeting Indianapolis, IN, May 2013. The authors have no funding or conflicts of interest to disclose. Address for correspondence: Jeffrey J. Cies, PharmD, MPH, BCPS-AQ ID, Critical Care and Infectious Diseases Clinical Pharmacist, St. Christopher’s Hospital for Children, 3601 A Street, Philadelphia, PA 19134-1095. E-mail: [email protected]. Copyright © 2014 by Lippincott Williams & Wilkins DOI: 10.1097/INF.0000000000000370
I
nfections are a major cause of death among critically ill patients.1 Early diagnosis and administration of antimicrobial agents for bacterial infections are paramount and have been shown to reduce morbidity and mortality in the pediatric and adult population.1–3 Therefore,
984 | www.pidj.com
assessment of the systemic inflammatory response to infection, crucial to management and outcome of these patients, is difficult with usual markers (ie, fever, leukocytosis, C-reactive protein). Even though a bacterial culture is the best method for diagnosing an infection, it does not indicate the host response well or differentiate between bacterial colonization and systemic complications like a systemic inflammatory response to infection or invasive bacterial infections.1 There are data demonstrating that procalcitonin (PCT), a precursor peptide of the hormone calcitonin,4 which rises specifically in bacterial processes,5 has utility in a wide range of adult bacterial infections.6,7 However, there are limited data on the general use of PCT in children and neonates. Therefore, the purpose of this study was to evaluate the utility of a cutoff value of 1 ng/mL as a marker of serious bacterial infection (SBI) in pediatric intensive care unit (ICU) patients.
MATERIALS AND METHODS This was a single-center, retrospective study that was conducted in a 189-bed freestanding children’s tertiary care teaching hospital with 33 critical care beds that provide care for children with burns, trauma, congenital heart disease and children on extra corporeal membrane oxygenation. This study protocol was approved by the Medical Institutional Review Board. All patients admitted to the pediatric ICU that had a PCT level obtained from December 1, 2011, through April 30, 2012, were included. After a literature review, in mid-2010, the use of PCT was adopted for use in patients admitted to any of the ICUs (eg, general ICU, cardiac ICU, burn ICU and step-down unit). There was no specific protocol, and PCT levels were obtained at the discretion of the primary critical care team caring for the patient in an effort to guide treatment and differentiate bacterial from nonbacterial infections. For the purpose of this study, a patient was considered to have a SBI if they had either a positive blood culture, a positive urine culture and a urinalysis with positive nitrites or leukocyte esterase and at least 10 white blood cells per high power field, a positive tracheal culture and gram stain with moderate or many white blood cells and a positive chest radiogram or a patient that received >5 days of therapeutic antibiotics. PCT concentrations were obtained using the VIDAS Brahms Mini-Vidas instrument (Biomerieux Inc, Durham, NC). Demographic and clinical characteristics were compared between the groups with a student’s t test for continuous variables and a χ2, Fisher’s exact test or Mann-Whitney U test for noncontinuous variables. A 2-sided significance level of α = 0.05 was used to determine statistical significance. Simple linear regression and a correlation analysis were used to test the association between PCT and bacterial infection. A receiver operator characteristic curve was also generated. All analyses were performed using IBM SPSS Version 20 (SPSS Inc., Chicago, IL).
RESULTS Two-hundred one patients with 332 PCT samples met inclusion criteria and were analyzed (Table 1). The median age of the population was 1.7 years (range 0 days to 24 years). Forty-seven (23.4%) patients had a positive bacterial culture and 63 (31.3%) patients had a positive viral culture leaving 91 (45.3%) patients without any positive culture in the population. Overall, 63 (31.3%) patients received a full treatment course of antimicrobials. There were 75 (37.3%) patients with a PCT ≥ 1 ng/mL (Table 2). Of the patients with a PCT ≥ 1 ng/mL, 24 (32%) had a positive viral culture and 28 (37.3%) had a positive bacterial culture. The type of positive bacterial culture were as follows; 7 blood, 3 urine, 11 tracheal aspirate and 11 other. Forty-six (61.3%) patients with a PCT ≥ 1 ng/mL received a full treatment course of at least one antimicrobial. When evaluating PCT against all positive cultures, there was a positive correlation between a PCT ≥1 ng/mL and a positive bacterial culture, Spearman’s Rho = 0.253, P 1 PCT level, % Positive bacterial culture, % Blood, % Urine, % Respiratory, % Other, % Positive viral culture, % Antibiotics > 5 days, %
Number, % 201 1.7 (0 days to 24 yrs) 36 (18) 6 (3) 4 (2) 25 (12) 14 (7) 40 (20) 46 (23) 28 (14) 2 (1) 6.44 (17.7) 190.3 1 (1–14) 65 (32.3) 47 (23.4) 7 (3.5) 6 (3) 27 (13.4) 15 (7.5) 63 (31.3) 63 (31.3)
BSI, blood stream infection; PNA, pneumonia; CNS, central nervous system process (seizures, abscess); SD, standard deviation; yrs, years.
TABLE 2. Culture Breakdown for Patients With PCT ≥ 1 ng/mL PCT ≥ 1
Number
# patients Positive bacterial culture, % Blood, % Urine, % Respiratory, % Other, % Positive viral culture, % Positive bacterial and viral culture, % Antibiotics > 5 days, %
75 28 (37.3) 7 (25) 3 (10.7) 11 (39.2) 11 (39.2) 24 (32) 7 (9.3) 46 (61.3)
was also a positive correlation between a PCT ≥1 ng/mL and receiving a treatment course of antimicrobials (Spearman’s Rho = 0.48, P
Cies and Chopra
ACKNOWLEDGMENTS The authors wish to thank Dr. Stephen Druhan of the Department of Radiology of Nationwide Children’s Hospital for his assistance in reviewing the cardiac MRI. REFERENCES 1. Schutze GE, Jacobs RF. Bartonella species (cat-scratch disease). In: Long SS, Pickering LK, Prober CG, eds. Principles and Practice of Pediatric Infectious Diseases. 4th ed. Philadelphia: Elsevier; 2012:856–861. 2. Spach DH, Kaplan SL. Microbiology, epidemiology, clinical manifestations, and diagnosis of cat scratch disease. In: Rose BD, ed. UpToDate. Waltham: UpToDate; 2013. 3. Holmberg M, Wesslen E, Hjelm C, et al. Bartonella spp. in a 60 year-old Swedish male with myocarditis who succumbed to sudden death [Abstract 31]. In: Program and abstracts of the 13th Sesquiannual Meeting of the American Society for Rickettsiology. Champion, PA. September 21–24, 1997. 4. Meininger GR, Nadasdy T, Hruban RH, et al. Chronic active myocarditis following acute Bartonella henselae infection (cat scratch disease). Am J Surg Pathol. 2001;25:1211–1214. 5. Wesslen L, Ehrenborg C, Holmberg M, et al. Subacute Bartonella infection in Swedish orienteers succumbing to sudden unexpected cardiac death or having malignant arrhythmias. Scand J Infect Dis. 2001;33: 429–438. 6. Pipili C, Katsogridakis K, Cholongitas E. Mycocarditis due to Bartonella henselae. South Med J. 2008;101:1186. 7. Skouri HN, Dec W, Friedrich MG, et al. Non-invasive imaging in myocarditis. J Am Coll Cardiol. 2006;48:2085–2093. 8. Kobayashi D, Aggarwal S, Kheiwa A, et al. Myopericarditis in children: elevated troponin I level does not predict outcome. Pediatr Cardiol. 2012;33:1040–1045. 9. Holmes AH, Greenough TC, Balady GJ, et al. Bartonella henselae endocarditis in an immunocompetent adult. Clin Infect Dis. 1995;21: 1004–1007.
PROCALCITONIN USE IN A PEDIATRIC INTENSIVE CARE UNIT Jeffrey J. Cies, PharmD, MPH, BCPS-AQ ID,*†‡ and Arun Chopra, MD§¶ Abstract: We evaluated whether procalcitonin (PCT) might aid diagnosing serious bacterial infections in a general pediatric intensive care unit population. Two-hundred and one patients accounted for 332 PCT samples. A PCT ≥1.45 ng/mL had a positive predictive value of 30%, a negative predictive value of 93% and a sensitivity of 72% and a specificity of 75%. These data suggest PCT can assist in identifying patients without serious bacterial infections and limit antimicrobial use. Key Words: procalcitonin, critical care, pediatric Accepted for publication April 4, 2014. From the *St. Christopher’s Hospital for Children, Philadelphia, PA; †Drexel University College of Medicine, Philadelphia, PA; ‡Alfred I duPont Hospital for Children, Wilmington, DE; §NYU Langone Medical Center, New York, NY; and ¶NYU School of Medicine, New York, NY. This work, in part, was presented as an abstract at the 22nd Annual Pediatric Pharmacy Advocacy Group Meeting Indianapolis, IN, May 2013. The authors have no funding or conflicts of interest to disclose. Address for correspondence: Jeffrey J. Cies, PharmD, MPH, BCPS-AQ ID, Critical Care and Infectious Diseases Clinical Pharmacist, St. Christopher’s Hospital for Children, 3601 A Street, Philadelphia, PA 19134-1095. E-mail: [email protected]. Copyright © 2014 by Lippincott Williams & Wilkins DOI: 10.1097/INF.0000000000000370
I
nfections are a major cause of death among critically ill patients.1 Early diagnosis and administration of antimicrobial agents for bacterial infections are paramount and have been shown to reduce morbidity and mortality in the pediatric and adult population.1–3 Therefore,
984 | www.pidj.com
assessment of the systemic inflammatory response to infection, crucial to management and outcome of these patients, is difficult with usual markers (ie, fever, leukocytosis, C-reactive protein). Even though a bacterial culture is the best method for diagnosing an infection, it does not indicate the host response well or differentiate between bacterial colonization and systemic complications like a systemic inflammatory response to infection or invasive bacterial infections.1 There are data demonstrating that procalcitonin (PCT), a precursor peptide of the hormone calcitonin,4 which rises specifically in bacterial processes,5 has utility in a wide range of adult bacterial infections.6,7 However, there are limited data on the general use of PCT in children and neonates. Therefore, the purpose of this study was to evaluate the utility of a cutoff value of 1 ng/mL as a marker of serious bacterial infection (SBI) in pediatric intensive care unit (ICU) patients.
MATERIALS AND METHODS This was a single-center, retrospective study that was conducted in a 189-bed freestanding children’s tertiary care teaching hospital with 33 critical care beds that provide care for children with burns, trauma, congenital heart disease and children on extra corporeal membrane oxygenation. This study protocol was approved by the Medical Institutional Review Board. All patients admitted to the pediatric ICU that had a PCT level obtained from December 1, 2011, through April 30, 2012, were included. After a literature review, in mid-2010, the use of PCT was adopted for use in patients admitted to any of the ICUs (eg, general ICU, cardiac ICU, burn ICU and step-down unit). There was no specific protocol, and PCT levels were obtained at the discretion of the primary critical care team caring for the patient in an effort to guide treatment and differentiate bacterial from nonbacterial infections. For the purpose of this study, a patient was considered to have a SBI if they had either a positive blood culture, a positive urine culture and a urinalysis with positive nitrites or leukocyte esterase and at least 10 white blood cells per high power field, a positive tracheal culture and gram stain with moderate or many white blood cells and a positive chest radiogram or a patient that received >5 days of therapeutic antibiotics. PCT concentrations were obtained using the VIDAS Brahms Mini-Vidas instrument (Biomerieux Inc, Durham, NC). Demographic and clinical characteristics were compared between the groups with a student’s t test for continuous variables and a χ2, Fisher’s exact test or Mann-Whitney U test for noncontinuous variables. A 2-sided significance level of α = 0.05 was used to determine statistical significance. Simple linear regression and a correlation analysis were used to test the association between PCT and bacterial infection. A receiver operator characteristic curve was also generated. All analyses were performed using IBM SPSS Version 20 (SPSS Inc., Chicago, IL).
RESULTS Two-hundred one patients with 332 PCT samples met inclusion criteria and were analyzed (Table 1). The median age of the population was 1.7 years (range 0 days to 24 years). Forty-seven (23.4%) patients had a positive bacterial culture and 63 (31.3%) patients had a positive viral culture leaving 91 (45.3%) patients without any positive culture in the population. Overall, 63 (31.3%) patients received a full treatment course of antimicrobials. There were 75 (37.3%) patients with a PCT ≥ 1 ng/mL (Table 2). Of the patients with a PCT ≥ 1 ng/mL, 24 (32%) had a positive viral culture and 28 (37.3%) had a positive bacterial culture. The type of positive bacterial culture were as follows; 7 blood, 3 urine, 11 tracheal aspirate and 11 other. Forty-six (61.3%) patients with a PCT ≥ 1 ng/mL received a full treatment course of at least one antimicrobial. When evaluating PCT against all positive cultures, there was a positive correlation between a PCT ≥1 ng/mL and a positive bacterial culture, Spearman’s Rho = 0.253, P 1 PCT level, % Positive bacterial culture, % Blood, % Urine, % Respiratory, % Other, % Positive viral culture, % Antibiotics > 5 days, %
Number, % 201 1.7 (0 days to 24 yrs) 36 (18) 6 (3) 4 (2) 25 (12) 14 (7) 40 (20) 46 (23) 28 (14) 2 (1) 6.44 (17.7) 190.3 1 (1–14) 65 (32.3) 47 (23.4) 7 (3.5) 6 (3) 27 (13.4) 15 (7.5) 63 (31.3) 63 (31.3)
BSI, blood stream infection; PNA, pneumonia; CNS, central nervous system process (seizures, abscess); SD, standard deviation; yrs, years.
TABLE 2. Culture Breakdown for Patients With PCT ≥ 1 ng/mL PCT ≥ 1
Number
# patients Positive bacterial culture, % Blood, % Urine, % Respiratory, % Other, % Positive viral culture, % Positive bacterial and viral culture, % Antibiotics > 5 days, %
75 28 (37.3) 7 (25) 3 (10.7) 11 (39.2) 11 (39.2) 24 (32) 7 (9.3) 46 (61.3)
was also a positive correlation between a PCT ≥1 ng/mL and receiving a treatment course of antimicrobials (Spearman’s Rho = 0.48, P
