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Published in: Critical Care 4/2006

Open Access 01-08-2006 | Research

Administration of antibiotics via the respiratory tract for the prevention of ICU-acquired pneumonia: a meta-analysis of comparative trials

Authors: Matthew E Falagas, Ilias I Siempos, Ioannis A Bliziotis, Argyris Michalopoulos

Published in: Critical Care | Issue 4/2006

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Abstract

Introduction

The administration of prophylactic antibiotics via the respiratory tract is one of several strategies for the prevention of intensive care unit (ICU)-acquired pneumonia. We systematically examined the available evidence regarding the effect of prophylactic antibiotics administered via the respiratory tract on the development of ICU-acquired pneumonia, mortality, colonization of the respiratory tract, emergence of antimicrobial resistance, and toxicity.

Methods

We searched the PubMed database (January 1950 to September 2005) and references from relevant articles to identify trials that provided comparative data regarding the above-mentioned outcomes. Two investigators independently performed the data extraction to calculate the effect of the studied intervention on clinically relevant outcomes.

Results

Our meta-analysis includes 8 comparative trials (5 randomized controlled trials (RCTs) and 3 non-randomized trials) studying gentamicin (3 trials), polymyxins (3 trials), tobramycin (1 trial), and ceftazidime (1 trial) that studied 1,877 patients. Our primary analysis, which included the 5 RCTs, revealed that ICU-acquired pneumonia was less common in the group of patients that received the antibiotic prophylaxis (odds ratio (OR) = 0.49, 95% confidence interval (CI) 0.32–0.76). No difference in mortality was found between the compared groups (OR = 0.86, 95% CI 0.55–1.32). Data were too limited to permit an analysis of colonization with Pseudomonas aeruginosa. A secondary analysis, adding the three non-randomized comparative trials, did not reveal substantially different results regarding ICU-acquired pneumonia and mortality, while fewer patients were colonized with P. aeruginosa in the group that received prophylaxis, compared to the group of patients that received no prophylaxis (OR = 0.51, 95% CI 0.30–0.86). No serious drug-related toxicity was noted. No meaningful systematic analysis of the evidence regarding the emergence of resistance could be performed in the studies included in our meta-analysis.

Conclusion

The limited available evidence supports that prophylactic administration of antibiotics via the respiratory tract is associated with reduction of occurrence of ICU-acquired pneumonia. However, there is evidence from non-comparative studies that this preventive strategy may lead to an increase in the emergence of resistant bacteria. Thus, further investigation, at least in ICU patients at high risk for development of ICU-acquired pneumonia, is warranted, including a more systematic evaluation of issues related to the emergence of resistance.
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Literature
1.
go back to reference Dodek P, Keenan S, Cook D, Heyland D, Jacka M, Hand L, Muscedere J, Foster D, Mehta N, Hall R, et al.: Evidence-based clinical practice guideline for the prevention of ventilator-associated pneumonia. Ann Intern Med 2004, 141: 305-313.CrossRefPubMed Dodek P, Keenan S, Cook D, Heyland D, Jacka M, Hand L, Muscedere J, Foster D, Mehta N, Hall R, et al.: Evidence-based clinical practice guideline for the prevention of ventilator-associated pneumonia. Ann Intern Med 2004, 141: 305-313.CrossRefPubMed
2.
go back to reference Kollef MH, Micek ST: Strategies to prevent antimicrobial resistance in the intensive care unit. Crit Care Med 2005, 33: 1845-1853. 10.1097/01.CCM.0000171849.04952.79CrossRefPubMed Kollef MH, Micek ST: Strategies to prevent antimicrobial resistance in the intensive care unit. Crit Care Med 2005, 33: 1845-1853. 10.1097/01.CCM.0000171849.04952.79CrossRefPubMed
3.
go back to reference Tablan OC, Anderson LJ, Arden NH, Breiman RF, Butler JC, McNeil MM: Guideline for prevention of nosocomial pneumonia. The Hospital Infection Control Practices Advisory Committee, Centers for Disease Control and Prevention. Infect Control Hosp Epidemiol 1994, 15: 587-627.CrossRefPubMed Tablan OC, Anderson LJ, Arden NH, Breiman RF, Butler JC, McNeil MM: Guideline for prevention of nosocomial pneumonia. The Hospital Infection Control Practices Advisory Committee, Centers for Disease Control and Prevention. Infect Control Hosp Epidemiol 1994, 15: 587-627.CrossRefPubMed
4.
go back to reference Tablan OC, Anderson LJ, Besser R, Bridges C, Hajjeh R: Guidelines for preventing health-care – associated pneumonia, 2003: recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee. MMWR Recomm Rep 2004, 53: 1-36.PubMed Tablan OC, Anderson LJ, Besser R, Bridges C, Hajjeh R: Guidelines for preventing health-care – associated pneumonia, 2003: recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee. MMWR Recomm Rep 2004, 53: 1-36.PubMed
5.
go back to reference Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ: Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996, 17: 1-12. 10.1016/0197-2456(95)00134-4CrossRefPubMed Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ: Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996, 17: 1-12. 10.1016/0197-2456(95)00134-4CrossRefPubMed
6.
go back to reference DerSimonian R, Laird N: Meta-analysis in clinical trials. Control Clin Trials 1986, 7: 177-188. 10.1016/0197-2456(86)90046-2CrossRefPubMed DerSimonian R, Laird N: Meta-analysis in clinical trials. Control Clin Trials 1986, 7: 177-188. 10.1016/0197-2456(86)90046-2CrossRefPubMed
7.
go back to reference Mantel N, Mocarelli P, Marocchi A, Brambilla P, Baretta R: Stratified analysis of multivariate clinical data: application of a Mantel-Haenszel approach. Stat Med 1983, 2: 259-266.CrossRefPubMed Mantel N, Mocarelli P, Marocchi A, Brambilla P, Baretta R: Stratified analysis of multivariate clinical data: application of a Mantel-Haenszel approach. Stat Med 1983, 2: 259-266.CrossRefPubMed
8.
go back to reference Mantel N, Haenszel W: Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959, 22: 719-748.PubMed Mantel N, Haenszel W: Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959, 22: 719-748.PubMed
10.
go back to reference Feeley TW, Du Moulin GC, Hedley-Whyte J, Bushnell LS, Gilbert JP, Feingold DS: Aerosol polymyxin and pneumonia in seriously ill patients. N Engl J Med 1975, 293: 471-475.CrossRefPubMed Feeley TW, Du Moulin GC, Hedley-Whyte J, Bushnell LS, Gilbert JP, Feingold DS: Aerosol polymyxin and pneumonia in seriously ill patients. N Engl J Med 1975, 293: 471-475.CrossRefPubMed
11.
go back to reference Greenfield S, Teres D, Bushnell LS, Hedley-Whyte J, Feingold DS: Prevention of gram-negative bacillary pneumonia using aerosol polymyxin as prophylaxis. I. Effect on the colonization pattern of the upper respiratory tract of seriously ill patients. J Clin Invest 1973, 52: 2935-2940.PubMedCentralCrossRefPubMed Greenfield S, Teres D, Bushnell LS, Hedley-Whyte J, Feingold DS: Prevention of gram-negative bacillary pneumonia using aerosol polymyxin as prophylaxis. I. Effect on the colonization pattern of the upper respiratory tract of seriously ill patients. J Clin Invest 1973, 52: 2935-2940.PubMedCentralCrossRefPubMed
12.
go back to reference Hoth JJ, Franklin GA, Stassen NA, Girard SM, Rodriguez RJ, Rodriguez JL: Prophylactic antibiotics adversely affect nosocomial pneumonia in trauma patients. J Trauma 2003, 55: 249-254.CrossRefPubMed Hoth JJ, Franklin GA, Stassen NA, Girard SM, Rodriguez RJ, Rodriguez JL: Prophylactic antibiotics adversely affect nosocomial pneumonia in trauma patients. J Trauma 2003, 55: 249-254.CrossRefPubMed
13.
go back to reference Klastersky J, Huysmans E, Weerts D, Hensgens C, Daneau D: Endotracheally administered gentamicin for the prevention of infections of the respiratory tract in patients with tracheostomy: a double-blind study. Chest 1974, 65: 650-654.CrossRefPubMed Klastersky J, Huysmans E, Weerts D, Hensgens C, Daneau D: Endotracheally administered gentamicin for the prevention of infections of the respiratory tract in patients with tracheostomy: a double-blind study. Chest 1974, 65: 650-654.CrossRefPubMed
14.
go back to reference Klastersky J, Hensgens C, Noterman J, Mouawad E, Meunier-Carpentier F: Endotracheal antibiotics for the prevention of tracheobronchial infections in tracheotomized unconscious patients. A comparative study of gentamicin and aminosidin-polymyxin B combination. Chest 1975, 68: 302-306.CrossRefPubMed Klastersky J, Hensgens C, Noterman J, Mouawad E, Meunier-Carpentier F: Endotracheal antibiotics for the prevention of tracheobronchial infections in tracheotomized unconscious patients. A comparative study of gentamicin and aminosidin-polymyxin B combination. Chest 1975, 68: 302-306.CrossRefPubMed
15.
go back to reference Klick JM, du Moulin GC, Hedley-Whyte J, Teres D, Bushnell LS, Feingold DS: Prevention of gram-negative bacillary pneumonia using polymyxin aerosol as prophylaxis. II. Effect on the incidence of pneumonia in seriously ill patients. J Clin Invest 1975, 55: 514-519.PubMedCentralCrossRefPubMed Klick JM, du Moulin GC, Hedley-Whyte J, Teres D, Bushnell LS, Feingold DS: Prevention of gram-negative bacillary pneumonia using polymyxin aerosol as prophylaxis. II. Effect on the incidence of pneumonia in seriously ill patients. J Clin Invest 1975, 55: 514-519.PubMedCentralCrossRefPubMed
16.
go back to reference Lepper MH, Kofman S, Blatt N, Dowling HF, Jackson GG: Effect of eight antibiotics used singly and in combination on the tracheal flora following tracheotomy in poliomyelitis. Antibiot Chemother 1954, 4: 829-843. Lepper MH, Kofman S, Blatt N, Dowling HF, Jackson GG: Effect of eight antibiotics used singly and in combination on the tracheal flora following tracheotomy in poliomyelitis. Antibiot Chemother 1954, 4: 829-843.
17.
go back to reference Lode H, Hoffken G, Kemmerich B, Schaberg T: Systemic and endotracheal antibiotic prophylaxis of nosocomial pneumonia in ICU. Intensive Care Med 1992,18(Suppl 1):S24-S27. 10.1007/BF01752973CrossRefPubMed Lode H, Hoffken G, Kemmerich B, Schaberg T: Systemic and endotracheal antibiotic prophylaxis of nosocomial pneumonia in ICU. Intensive Care Med 1992,18(Suppl 1):S24-S27. 10.1007/BF01752973CrossRefPubMed
18.
go back to reference Rathgeber J, Zielmann S, Panzer C, Burchardi H: [Prevention of pneumonia by endotracheal micronebulization of tobramycin]. Anasthesiol Intensivmed Notfallmed Schmerzther 1993, 28: 23-29.CrossRefPubMed Rathgeber J, Zielmann S, Panzer C, Burchardi H: [Prevention of pneumonia by endotracheal micronebulization of tobramycin]. Anasthesiol Intensivmed Notfallmed Schmerzther 1993, 28: 23-29.CrossRefPubMed
19.
go back to reference Rouby JJ, Poete P, Martin dL, Nicolas MH, Bodin L, Jarlier V, Korinek AM, Viars P: Prevention of gram negative nosocomial bronchopneumonia by intratracheal colistin in critically ill patients. Histologic and bacteriologic study. Intensive Care Med 1994, 20: 187-192. 10.1007/BF01704698CrossRefPubMed Rouby JJ, Poete P, Martin dL, Nicolas MH, Bodin L, Jarlier V, Korinek AM, Viars P: Prevention of gram negative nosocomial bronchopneumonia by intratracheal colistin in critically ill patients. Histologic and bacteriologic study. Intensive Care Med 1994, 20: 187-192. 10.1007/BF01704698CrossRefPubMed
20.
go back to reference Vogel F, Werner H, Exner M, Marx M: [Prophylaxis and treatment of respiratory tract infection in ventilated patients by endotracheal administration of aminoglycosides (author's transl)]. Dtsch Med Wochenschr 1981, 106: 898-903.CrossRefPubMed Vogel F, Werner H, Exner M, Marx M: [Prophylaxis and treatment of respiratory tract infection in ventilated patients by endotracheal administration of aminoglycosides (author's transl)]. Dtsch Med Wochenschr 1981, 106: 898-903.CrossRefPubMed
21.
go back to reference Wood GC, Boucher BA, Croce MA, Hanes SD, Herring VL, Fabian TC: Aerosolized ceftazidime for prevention of ventilator-associated pneumonia and drug effects on the proinflammatory response in critically ill trauma patients. Pharmacotherapy 2002, 22: 972-982. 10.1592/phco.22.12.972.33596CrossRefPubMed Wood GC, Boucher BA, Croce MA, Hanes SD, Herring VL, Fabian TC: Aerosolized ceftazidime for prevention of ventilator-associated pneumonia and drug effects on the proinflammatory response in critically ill trauma patients. Pharmacotherapy 2002, 22: 972-982. 10.1592/phco.22.12.972.33596CrossRefPubMed
22.
go back to reference Crouch TW, Higuchi JH, Coalson JJ, Johanson WG Jr: Pathogenesis and prevention of nosocomial pneumonia in a nonhuman primate model of acute respiratory failure. Am Rev Respir Dis 1984, 130: 502-504.PubMed Crouch TW, Higuchi JH, Coalson JJ, Johanson WG Jr: Pathogenesis and prevention of nosocomial pneumonia in a nonhuman primate model of acute respiratory failure. Am Rev Respir Dis 1984, 130: 502-504.PubMed
23.
go back to reference Le Conte P, Potel G, Peltier P, Horeau D, Caillon J, Juvin ME, Kergueris MF, Bugnon D, Baron D: Lung distribution and pharmacokinetics of aerosolized tobramycin. Am Rev Respir Dis 1993, 147: 1279-1282.CrossRefPubMed Le Conte P, Potel G, Peltier P, Horeau D, Caillon J, Juvin ME, Kergueris MF, Bugnon D, Baron D: Lung distribution and pharmacokinetics of aerosolized tobramycin. Am Rev Respir Dis 1993, 147: 1279-1282.CrossRefPubMed
24.
go back to reference Odio W, Van Laer E, Klastersky J: Concentrations of gentamicin in bronchial secretions after intramuscular and endotracheal administration. J Clin Pharmacol 1975, 15: 518-524.CrossRefPubMed Odio W, Van Laer E, Klastersky J: Concentrations of gentamicin in bronchial secretions after intramuscular and endotracheal administration. J Clin Pharmacol 1975, 15: 518-524.CrossRefPubMed
25.
go back to reference Wood GC, Boucher BA: Aerosolized antimicrobial therapy in acutely ill patients. Pharmacotherapy 2000, 20: 166-181. 10.1592/phco.20.3.166.34783CrossRefPubMed Wood GC, Boucher BA: Aerosolized antimicrobial therapy in acutely ill patients. Pharmacotherapy 2000, 20: 166-181. 10.1592/phco.20.3.166.34783CrossRefPubMed
26.
go back to reference Orriols R, Roig J, Ferrer J, Sampol G, Rosell A, Ferrer A, Vallano A: Inhaled antibiotic therapy in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa . Respir Med 1999, 93: 476-480. 10.1016/S0954-6111(99)90090-2CrossRefPubMed Orriols R, Roig J, Ferrer J, Sampol G, Rosell A, Ferrer A, Vallano A: Inhaled antibiotic therapy in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa . Respir Med 1999, 93: 476-480. 10.1016/S0954-6111(99)90090-2CrossRefPubMed
27.
go back to reference Drobnic ME, Sune P, Montoro JB, Ferrer A, Orriols R: Inhaled tobramycin in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection with Pseudomonas aeruginosa . Ann Pharmacother 2005, 39: 39-44.CrossRefPubMed Drobnic ME, Sune P, Montoro JB, Ferrer A, Orriols R: Inhaled tobramycin in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection with Pseudomonas aeruginosa . Ann Pharmacother 2005, 39: 39-44.CrossRefPubMed
28.
go back to reference Barker AF, Couch L, Fiel SB, Gotfried MH, Ilowite J, Meyer KC, O'Donnell A, Sahn SA, Smith LJ, Stewart JO, et al.: Tobramycin solution for inhalation reduces sputum Pseudomonas aeruginosa density in bronchiectasis. Am J Respir Crit Care Med 2000, 162: 481-485.CrossRefPubMed Barker AF, Couch L, Fiel SB, Gotfried MH, Ilowite J, Meyer KC, O'Donnell A, Sahn SA, Smith LJ, Stewart JO, et al.: Tobramycin solution for inhalation reduces sputum Pseudomonas aeruginosa density in bronchiectasis. Am J Respir Crit Care Med 2000, 162: 481-485.CrossRefPubMed
29.
30.
go back to reference Melani AS, Di Gregorio A: Acute respiratory failure due to gentamicin aerosolization. Monaldi Arch Chest Dis 1998, 53: 274-276.PubMed Melani AS, Di Gregorio A: Acute respiratory failure due to gentamicin aerosolization. Monaldi Arch Chest Dis 1998, 53: 274-276.PubMed
31.
go back to reference Paterson JW, Sudlow MF, Walker SR: Blood-levels of fluorinated hydrocarbons in asthmatic patients after inhalation of pressurised aerosols. Lancet 1971, 2: 565-568. 10.1016/S0140-6736(71)92149-0CrossRefPubMed Paterson JW, Sudlow MF, Walker SR: Blood-levels of fluorinated hydrocarbons in asthmatic patients after inhalation of pressurised aerosols. Lancet 1971, 2: 565-568. 10.1016/S0140-6736(71)92149-0CrossRefPubMed
32.
go back to reference Levine BA, Petroff PA, Slade CL, Pruitt BA Jr: Prospective trials of dexamethasone and aerosolized gentamicin in the treatment of inhalation injury in the burned patient. J Trauma 1978, 18: 188-193.CrossRefPubMed Levine BA, Petroff PA, Slade CL, Pruitt BA Jr: Prospective trials of dexamethasone and aerosolized gentamicin in the treatment of inhalation injury in the burned patient. J Trauma 1978, 18: 188-193.CrossRefPubMed
33.
go back to reference Brown RB, Phillips D, Barker MJ, Pieczarka R, Sands M, Teres D: Outbreak of nosocomial Flavobacterium meningosepticum respiratory infections associated with use of aerosolized polymyxin B. Am J Infect Control 1989, 17: 121-125. 10.1016/0196-6553(89)90197-1CrossRefPubMed Brown RB, Phillips D, Barker MJ, Pieczarka R, Sands M, Teres D: Outbreak of nosocomial Flavobacterium meningosepticum respiratory infections associated with use of aerosolized polymyxin B. Am J Infect Control 1989, 17: 121-125. 10.1016/0196-6553(89)90197-1CrossRefPubMed
34.
go back to reference Alothman GA, Ho B, Alsaadi MM, Ho SL, O'Drowsky L, Louca E, Coates AL: Bronchial constriction and inhaled colistin in cystic fibrosis. Chest 2005, 127: 522-529. 10.1378/chest.127.2.522CrossRefPubMed Alothman GA, Ho B, Alsaadi MM, Ho SL, O'Drowsky L, Louca E, Coates AL: Bronchial constriction and inhaled colistin in cystic fibrosis. Chest 2005, 127: 522-529. 10.1378/chest.127.2.522CrossRefPubMed
35.
36.
go back to reference Falagas ME, Bliziotis IA, Siempos II: Attributable mortality of Acinetobacter baumannii infections in critically ill patients: a systematic review of matched cohort and case-control studies. Crit Care 2006, 10: R48. 10.1186/cc4869PubMedCentralCrossRefPubMed Falagas ME, Bliziotis IA, Siempos II: Attributable mortality of Acinetobacter baumannii infections in critically ill patients: a systematic review of matched cohort and case-control studies. Crit Care 2006, 10: R48. 10.1186/cc4869PubMedCentralCrossRefPubMed
Metadata
Title
Administration of antibiotics via the respiratory tract for the prevention of ICU-acquired pneumonia: a meta-analysis of comparative trials
Authors
Matthew E Falagas
Ilias I Siempos
Ioannis A Bliziotis
Argyris Michalopoulos
Publication date
01-08-2006
Publisher
BioMed Central
Published in
Critical Care / Issue 4/2006
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc5032

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