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

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.