of AAT deficiency. Thus, deficiency variants (S, Z, and rare) would likely be overrepresented relative to the general population in these studies.1,3 Nevertheless, determinations of serum concentration reference intervals within each phenotype/genotype and the relative frequency distribution of different deficiency alleles within these studies can be considered valid. Joshua A. Bornhorst, PhD Little Rock, AR Dina N. Greene, PhD Berkeley, CA Edward R. Ashwood, MD David G. Grenache, PhD Salt Lake City, UT Affiliations: From the Department of Pathology (Dr Bornhorst), University of Arkansas for Medical Sciences; The Permanente Medical Group Regional Laboratories (Dr Greene), Kaiser Permanente Northern California; Department of Pathology (Drs Ashwood and Grenache), University of Utah School of Medicine; and ARUP Laboratories Institute of Clinical and Experimental Pathology (Drs Ashwood and Grenache). Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Bornhorst has received speaking honorarium from CSL Behring. Drs Greene, Ashwood, and Grenache have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Correspondence to: Joshua A. Bornhorst, PhD, University of Arkansas for Medical Sciences, 4301 W Markham St 502, Little Rock, AR 72205; e-mail: [email protected] © 2013 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.13-1974
References 1. Bornhorst JA, Greene DN, Ashwood ER, Grenache DG. a1-Antitrypsin phenotypes and associated serum protein concentrations in a large clinical population. Chest. 2013;143(4): 1000-1008. 2. Ferrarotti I, Thun GA, Zorzetto M, et al. Serum levels and genotype distribution of a1-antitrypsin in the general population. Thorax. 2012;67(8):669-674. 3. Donato LJ, Jenkins SM, Smith C, Katzmann JA, Snyder MR. Reference and interpretive ranges for a(1)-antitrypsin quantitation by phenotype in adult and pediatric populations. Am J Clin Pathol. 2012;138(3):398-405. 4. Bornhorst JA, Calderon FR, Procter M, Tang W, Ashwood ER, Mao R. Genotypes and serum concentrations of human alpha1-antitrypsin “P” protein variants in a clinical population. J Clin Pathol. 2007;60(10):1124-1128. 5. Zorzetto M, Russi E, Senn O, et al; SAPALDIA Team. SERPINA1 gene variants in individuals from the general population with reduced alpha1-antitrypsin concentrations. Clin Chem. 2008;54(8):1331-1338.
Antibiotic Prophylaxis for Ventilator-Associated Pneumonia More Is Less or Less Is More? To the Editor: The increasing prevalence of antibiotic resistance is of global concern. With few antibiotic agents in development,1 there is an increasing need for antibiotic stewardship. This is relevant in the
ICU where patients receive a large burden of antibiotics and are at risk for infection from antibiotic-resistant pathogens. There is a need to improve antibiotic stewardship in patients with suspected ventilator-associated pneumonia (VAP). Because infection is confirmed by positive culture results in about 30% of patients, the implication is that patients commonly receive antibiotics for noninfective respiratory compromise. The report by Vallés et al2 in a recent issue of CHEST (May 2013) adds complexity to the difficulties facing clinicians who balance antibiotic stewardship with the best outcome for the patient. This study reported a fall in VAP associated with prophylactic use of a single dose of antibiotics administered at the time of intubation in comatose patients. Data from the United States over the same period reported declining VAP rates in all patient groups.3 The apparent fall in VAP rates has led to debate about whether this represents the success of prevention strategies or changes in the quality of surveillance and reporting. These results need to be validated in a randomized controlled trial before being implemented in routine practice. Vallés et al2 acknowledged that the main risk of implementing widespread prophylactic antibiotics in the ICU is the emergence of antibiotic-resistant pathogens. Although the choice of antibiotic in this study covers the organisms commonly colonizing sites of potential inoculum before admission to the hospital, this cannot be assumed for all patient groups. The oropharynx of elderly patients admitted from inpatient wards or long-term-care facilities often is colonized by gram-negative bacilli4 and could be at risk for becoming colonized with resistant pathogens following antibiotic exposure. Vallés et al2 did not find an increase in resistant pathogens in the late-onset VAP group, but they did not perform surveillance cultures. Given that this was a small, single-center study, it does not provide sufficient evidence to exclude the possibility that the intervention may promote antibiotic resistance. The apparent reduction in early VAP in comatose patients, although an interesting finding, may be a benefit for a patient group for whom the consequences of VAP are less severe.5 Although these benefits are of potential value, they require confirmation in late VAP for which the clinical consequences are more severe. Ultimately, the aim remains to find better ways of preventing VAP that do not rely on the use of antibiotics. Tom Hellyer, MD Newcastle upon Tyne, Scotland Andrew Conway Morris, MD, PhD Edinburgh, Scotland A. John Simpson, MD, PhD Newcastle upon Tyne, Scotland Affiliations: From the Institute of Cellular Medicine (Dr Hellyer and Prof Simpson), Newcastle University; and University of Edinburgh/MRC Centre for Inflammation Research (Dr Conway Morris). Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Conway Morris has received grants from the Wellcome Trust and UK Department of Health for the study of diagnostic techniques in ventilatorassociated pneumonia. Prof Simpson has received funds to attend educational conferences (for travel, accommodation, and registration) from GlaxoSmithKline and Boehringer Ingelheim GmbH; delivered independent lectures at events sponsored by GlaxoSmithKline and Astellas Pharma Inc; and is a coinvestigator with BD on independent, noncommercial grants. Dr Hellyer has reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Correspondence to: Tom Hellyer, MD, Fourth Floor, William Leech Building, Medical School, Newcastle University, Framlington Pl, Newcastle upon Tyne, NE2 4HH, Scotland; e-mail: thomas.hellyer@ ncl.ac.uk
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© 2013 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.13-1478
References 1. Spellberg B, Powers JH, Brass EP, Miller LG, Edwards JE Jr. Trends in antimicrobial drug development: implications for the future. Clin Infect Dis. 2004;38(9):1279-1286. 2. Vallés J, Peredo R, Burgueño MJ, et al. Efficacy of single-dose antibiotic against early-onset pneumonia in comatose patients who are ventilated. Chest. 2013;143(5):1219-1225. 3. Dudeck MA, Horan TC, Peterson KD, et al. National Healthcare Safety Network (NHSN) Report, data summary for 2010, device-associated module. Am J Infect Control. 2011;39(10): 798-816. 4. Palmer LB, Albulak K, Fields S, Filkin AM, Simon S, Smaldone GC. Oral clearance and pathogenic oropharyngeal colonization in the elderly. Am J Respir Crit Care Med. 2001;164(3): 464-468. 5. Cook A, Norwood S, Berne J. Ventilator-associated pneumonia is more common and of less consequence in trauma patients compared with other critically ill patients. J Trauma. 2010; 69(5):1083-1091.
the ICU decreased (from 60% in control subjects to 30% in the prophylaxis group).1 Rational antibiotic prescription is conceived to optimize antimicrobial therapy, to assure cost-effective therapy while containing bacterial resistance. Although our strategy needs to be further evaluated in a randomized clinical trial, antibiotic stewardship can be easily implemented with a single dose. Jordi Vallés, MD, PhD Ignacio Martin-Loeches, MD, PhD Barcelona, Spain Affiliations: From the Critical Care Department, Corporació Parc Taulí. Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Correspondence to: Jordi Vallés, MD, PhD, Corporació Parc Taulí - Critical Care Department, Parc Tauli s/n, Sabadell, Barcelona 08208, Spain; e-mail: [email protected] © 2013 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.13-1576
References
Response To the Editor: We thank Dr Hellyer and colleagues for their comments regarding our article on prophylactic use of a single dose of antibiotic administered at the time of intubation in comatose patients.1 We agree that the excess of antibiotic use is associated with a higher risk of acquisition of multiple drug-resistant pathogens. Therefore, in our article, the goal of a prophylactic strategy is focused on a very particular population of comatose patients who are intubated in emergency situations. This group of patients presents a high incidence of early ventilator-associated pneumonia (VAP) (50%-60%),2,3 and, based on the American Thoracic Society/Infectious Diseases Society of America recommendations, it is suggested that prophylactic antibiotic use might be administered within the first 24 h.4 In our study, to rapidly decrease the bacterial burden during intubation, we decided to focus the period of administration of antibiotic within the first 4 h after intubation. The association of developing resistances to antibiotics has been recognized with the use of prolonged treatments. Furthermore, significant differences in antibiotic resistances have been documented when surgical patients received antibiotic prophylaxis for . 48 h.5 Interestingly, this was the main difference with previous studies that administered more than only one single dose of antibiotic. We have to acknowledge that with the use of our strategy, the outcome was not different between patients who received prophylaxis and those who did not. However, it is important to highlight the reduction in antibiotic pressure. Dead bugs do not mutate, and, therefore, avoiding early-onset VAP episodes will help avoid prescribing antibiotic therapy with ceftriaxone, quinolone, ampicillin/sulbactam, or ertapenem for 5 to 7 days based on the current American Thoracic Society/Infectious Diseases Society of America guidelines recommendation. We agree that we should be restrictive with the use of broadspectrum antibiotics in ICU settings to reduce the acquisition of multiple drug-resistant pathogens. Therefore, we strongly believe that with the use of a single antibiotic dose, the incidence of early VAP decreased and consequently the antibiotic consumption in
1. Vallés J, Peredo R, Burgueño MJ, et al. Efficacy of singledose antibiotic against early-onset pneumonia in comatose patients who are ventilated. Chest. 2013;143(5):1219-1225. 2. Acquarolo A, Urli T, Perone G, Giannotti C, Candiani A, Latronico N. Antibiotic prophylaxis of early onset pneumonia in critically ill comatose patients. A randomized study. Intensive Care Med. 2005;31(4):510-516. 3. Perbet S, Mongardon N, Dumas F, et al. Early-onset pneumonia after cardiac arrest: characteristics, risk factors and influence on prognosis. Am J Respir Crit Care Med. 2011; 184(9):1048-1054. 4. American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospitalacquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005;171(4):388-416. 5. Habarth S, Samore MH, Lichtenberg D, Carmeli Y. Prolonged antibiotic prophylaxis after cardiovascular surgery and its effect on surgical site infection and antimicrobial resistence. Circulation. 2000;101(25):2916-2921.
Thoracic Ultrasound Guidance for Access to Pleural, Peritoneal, and Pericardial Space To the Editor: A great contribution to patients’ care and safety of procedures is provided by ultrasound guidance in several interventions. Better visualization of the needle insertion site for thoracentesis, pericardiocentesis, and paracentesis is possible with ultrasound, reducing the risk of complications and their associated costs. This subject is very well presented in the recent report in CHEST (February 2013) by Mercaldi and Lanes,1 which demonstrates that ultrasound guidance is associated with decreased risk of pneumothorax with thoracentesis and of bleeding complications with paracentesis, allowing a measurable lowering in hospitalization costs. Their contribution is particularly valuable since, seemingly, echo guidance is not sufficiently in use worldwide.
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References 1. Bornhorst JA, Greene DN, Ashwood ER, Grenache DG. a1-Antitrypsin phenotypes and associated serum protein concentrations in a large clinical population. Chest. 2013;143(4): 1000-1008. 2. Ferrarotti I, Thun GA, Zorzetto M, et al. Serum levels and genotype distribution of a1-antitrypsin in the general population. Thorax. 2012;67(8):669-674. 3. Donato LJ, Jenkins SM, Smith C, Katzmann JA, Snyder MR. Reference and interpretive ranges for a(1)-antitrypsin quantitation by phenotype in adult and pediatric populations. Am J Clin Pathol. 2012;138(3):398-405. 4. Bornhorst JA, Calderon FR, Procter M, Tang W, Ashwood ER, Mao R. Genotypes and serum concentrations of human alpha1-antitrypsin “P” protein variants in a clinical population. J Clin Pathol. 2007;60(10):1124-1128. 5. Zorzetto M, Russi E, Senn O, et al; SAPALDIA Team. SERPINA1 gene variants in individuals from the general population with reduced alpha1-antitrypsin concentrations. Clin Chem. 2008;54(8):1331-1338.
Antibiotic Prophylaxis for Ventilator-Associated Pneumonia More Is Less or Less Is More? To the Editor: The increasing prevalence of antibiotic resistance is of global concern. With few antibiotic agents in development,1 there is an increasing need for antibiotic stewardship. This is relevant in the
ICU where patients receive a large burden of antibiotics and are at risk for infection from antibiotic-resistant pathogens. There is a need to improve antibiotic stewardship in patients with suspected ventilator-associated pneumonia (VAP). Because infection is confirmed by positive culture results in about 30% of patients, the implication is that patients commonly receive antibiotics for noninfective respiratory compromise. The report by Vallés et al2 in a recent issue of CHEST (May 2013) adds complexity to the difficulties facing clinicians who balance antibiotic stewardship with the best outcome for the patient. This study reported a fall in VAP associated with prophylactic use of a single dose of antibiotics administered at the time of intubation in comatose patients. Data from the United States over the same period reported declining VAP rates in all patient groups.3 The apparent fall in VAP rates has led to debate about whether this represents the success of prevention strategies or changes in the quality of surveillance and reporting. These results need to be validated in a randomized controlled trial before being implemented in routine practice. Vallés et al2 acknowledged that the main risk of implementing widespread prophylactic antibiotics in the ICU is the emergence of antibiotic-resistant pathogens. Although the choice of antibiotic in this study covers the organisms commonly colonizing sites of potential inoculum before admission to the hospital, this cannot be assumed for all patient groups. The oropharynx of elderly patients admitted from inpatient wards or long-term-care facilities often is colonized by gram-negative bacilli4 and could be at risk for becoming colonized with resistant pathogens following antibiotic exposure. Vallés et al2 did not find an increase in resistant pathogens in the late-onset VAP group, but they did not perform surveillance cultures. Given that this was a small, single-center study, it does not provide sufficient evidence to exclude the possibility that the intervention may promote antibiotic resistance. The apparent reduction in early VAP in comatose patients, although an interesting finding, may be a benefit for a patient group for whom the consequences of VAP are less severe.5 Although these benefits are of potential value, they require confirmation in late VAP for which the clinical consequences are more severe. Ultimately, the aim remains to find better ways of preventing VAP that do not rely on the use of antibiotics. Tom Hellyer, MD Newcastle upon Tyne, Scotland Andrew Conway Morris, MD, PhD Edinburgh, Scotland A. John Simpson, MD, PhD Newcastle upon Tyne, Scotland Affiliations: From the Institute of Cellular Medicine (Dr Hellyer and Prof Simpson), Newcastle University; and University of Edinburgh/MRC Centre for Inflammation Research (Dr Conway Morris). Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Conway Morris has received grants from the Wellcome Trust and UK Department of Health for the study of diagnostic techniques in ventilatorassociated pneumonia. Prof Simpson has received funds to attend educational conferences (for travel, accommodation, and registration) from GlaxoSmithKline and Boehringer Ingelheim GmbH; delivered independent lectures at events sponsored by GlaxoSmithKline and Astellas Pharma Inc; and is a coinvestigator with BD on independent, noncommercial grants. Dr Hellyer has reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Correspondence to: Tom Hellyer, MD, Fourth Floor, William Leech Building, Medical School, Newcastle University, Framlington Pl, Newcastle upon Tyne, NE2 4HH, Scotland; e-mail: thomas.hellyer@ ncl.ac.uk
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Correspondence
© 2013 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.13-1478
References 1. Spellberg B, Powers JH, Brass EP, Miller LG, Edwards JE Jr. Trends in antimicrobial drug development: implications for the future. Clin Infect Dis. 2004;38(9):1279-1286. 2. Vallés J, Peredo R, Burgueño MJ, et al. Efficacy of single-dose antibiotic against early-onset pneumonia in comatose patients who are ventilated. Chest. 2013;143(5):1219-1225. 3. Dudeck MA, Horan TC, Peterson KD, et al. National Healthcare Safety Network (NHSN) Report, data summary for 2010, device-associated module. Am J Infect Control. 2011;39(10): 798-816. 4. Palmer LB, Albulak K, Fields S, Filkin AM, Simon S, Smaldone GC. Oral clearance and pathogenic oropharyngeal colonization in the elderly. Am J Respir Crit Care Med. 2001;164(3): 464-468. 5. Cook A, Norwood S, Berne J. Ventilator-associated pneumonia is more common and of less consequence in trauma patients compared with other critically ill patients. J Trauma. 2010; 69(5):1083-1091.
the ICU decreased (from 60% in control subjects to 30% in the prophylaxis group).1 Rational antibiotic prescription is conceived to optimize antimicrobial therapy, to assure cost-effective therapy while containing bacterial resistance. Although our strategy needs to be further evaluated in a randomized clinical trial, antibiotic stewardship can be easily implemented with a single dose. Jordi Vallés, MD, PhD Ignacio Martin-Loeches, MD, PhD Barcelona, Spain Affiliations: From the Critical Care Department, Corporació Parc Taulí. Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Correspondence to: Jordi Vallés, MD, PhD, Corporació Parc Taulí - Critical Care Department, Parc Tauli s/n, Sabadell, Barcelona 08208, Spain; e-mail: [email protected] © 2013 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.13-1576
References
Response To the Editor: We thank Dr Hellyer and colleagues for their comments regarding our article on prophylactic use of a single dose of antibiotic administered at the time of intubation in comatose patients.1 We agree that the excess of antibiotic use is associated with a higher risk of acquisition of multiple drug-resistant pathogens. Therefore, in our article, the goal of a prophylactic strategy is focused on a very particular population of comatose patients who are intubated in emergency situations. This group of patients presents a high incidence of early ventilator-associated pneumonia (VAP) (50%-60%),2,3 and, based on the American Thoracic Society/Infectious Diseases Society of America recommendations, it is suggested that prophylactic antibiotic use might be administered within the first 24 h.4 In our study, to rapidly decrease the bacterial burden during intubation, we decided to focus the period of administration of antibiotic within the first 4 h after intubation. The association of developing resistances to antibiotics has been recognized with the use of prolonged treatments. Furthermore, significant differences in antibiotic resistances have been documented when surgical patients received antibiotic prophylaxis for . 48 h.5 Interestingly, this was the main difference with previous studies that administered more than only one single dose of antibiotic. We have to acknowledge that with the use of our strategy, the outcome was not different between patients who received prophylaxis and those who did not. However, it is important to highlight the reduction in antibiotic pressure. Dead bugs do not mutate, and, therefore, avoiding early-onset VAP episodes will help avoid prescribing antibiotic therapy with ceftriaxone, quinolone, ampicillin/sulbactam, or ertapenem for 5 to 7 days based on the current American Thoracic Society/Infectious Diseases Society of America guidelines recommendation. We agree that we should be restrictive with the use of broadspectrum antibiotics in ICU settings to reduce the acquisition of multiple drug-resistant pathogens. Therefore, we strongly believe that with the use of a single antibiotic dose, the incidence of early VAP decreased and consequently the antibiotic consumption in
1. Vallés J, Peredo R, Burgueño MJ, et al. Efficacy of singledose antibiotic against early-onset pneumonia in comatose patients who are ventilated. Chest. 2013;143(5):1219-1225. 2. Acquarolo A, Urli T, Perone G, Giannotti C, Candiani A, Latronico N. Antibiotic prophylaxis of early onset pneumonia in critically ill comatose patients. A randomized study. Intensive Care Med. 2005;31(4):510-516. 3. Perbet S, Mongardon N, Dumas F, et al. Early-onset pneumonia after cardiac arrest: characteristics, risk factors and influence on prognosis. Am J Respir Crit Care Med. 2011; 184(9):1048-1054. 4. American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospitalacquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005;171(4):388-416. 5. Habarth S, Samore MH, Lichtenberg D, Carmeli Y. Prolonged antibiotic prophylaxis after cardiovascular surgery and its effect on surgical site infection and antimicrobial resistence. Circulation. 2000;101(25):2916-2921.
Thoracic Ultrasound Guidance for Access to Pleural, Peritoneal, and Pericardial Space To the Editor: A great contribution to patients’ care and safety of procedures is provided by ultrasound guidance in several interventions. Better visualization of the needle insertion site for thoracentesis, pericardiocentesis, and paracentesis is possible with ultrasound, reducing the risk of complications and their associated costs. This subject is very well presented in the recent report in CHEST (February 2013) by Mercaldi and Lanes,1 which demonstrates that ultrasound guidance is associated with decreased risk of pneumothorax with thoracentesis and of bleeding complications with paracentesis, allowing a measurable lowering in hospitalization costs. Their contribution is particularly valuable since, seemingly, echo guidance is not sufficiently in use worldwide.
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