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

Abstract

Introduction: The administration of prophylactic antibiotics via the respiratory tract is one of several strategies for the prevention of 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 (1/1950 to 9/2005) 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: 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 were included in our meta-analysis. Our primary analysis that included the 5 RCTs, revealed that ICU-acquired pneumonia was less common in the group of patients that received the antibiotic prophylaxis (OR = 0.49, 95% CI 0.32-0.76). No difference in mortality was found between the compared groups (OR = 0.86, 95% CI 0.55-1.32). There were limited data to permit an analysis of colonization with Pseudomonas aeruginosa. A secondary analysis by adding the 3 non-randomized comparative trials did not reveal substantially different results regarding ICU-acquired pneumonia and mortality, while fewer patients were colonized with Pseudomonas 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.

Conclusions: 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.

Figure 1

Flow diagram of reviewed articles.

Figure 2

Odds ratios of mortality between patients who received antibiotic prophylaxis via the respiratory tract and those who received placebo or no therapy. (a) Primary analysis (only randomized controlled trials); (b) secondary analysis (including non-randomized trials). Vertical line = 'no difference' point in mortality between the two regimens. Horizontal lines = 95% confidence interval. Square = odds ratio; the size of each square denotes the proportion of information given by each trial. Diamond/triangle = pooled odds ratio for all studies.

Figure 3

Odds ratios of intensive care unit-acquired pneumonia between patients who received antibiotic prophylaxis via the respiratory tract and those who received placebo or no therapy. (a) Primary analysis (only randomized controlled trials); (b) secondary analysis (including non-randomized trials). Vertical line = 'no difference' point in intensive care unit-acquired pneumonia between the two regimens. Horizontal lines = 95% confidence interval. Square = odds ratio; the size of each square denotes the proportion of information given by each trial. Diamond/triangle = pooled odds ratio for all studies.