Health Technology Assessment Volume: 7, Issue: 27, Published in September 2003

Health Technology Assessment Volume: 9, Issue: 26, Published in July 2005

Objective: To determine whether antibiotic prophylaxis reduces respiratory tract infections and overall mortality in unselected critically ill adult patients. Design: Meta-analysis of randomised controlled trials from 1984 and 1996 that compared different forms of antibiotic prophylaxis used to reduce respiratory tract infections and mortality with aggregate data and, in a subset of trials, data from individual patients. Subjects: Unselected critically ill adult patients; 5727 patients for aggregate data meta-analysis, 4343 for confirmatory meta-analysis with data from individual patients. Main outcome measures: Respiratory tract infections and total mortality. Results: Two categories of eligible trials were defined: topical plus systemic antibiotics versus no treatment and topical preparation with or without a systemic antibiotic versus a systemic agent or placebo. Estimates from aggregate data meta-analysis of 16 trials (3361 patients) that tested combined treatment indicated a strong significant reduction in infection (odds ratio 0.35; 95% confidence interval 0.29 to 0.41) and total mortality (0.80; 0.69 to 0.93). With this treatment five and 23 patients would need to be treated to prevent one infection and one death, respectively. Similar analysis of 17 trials (2366 patients) that tested only topical antibiotics indicated a clear reduction in infection (0.56; 0.46 to 0.68) without a significant effect on total mortality (1.01; 0.84 to 1.22). Analysis of data from individual patients yielded similar results. No significant differences in treatment effect by major subgroups of patients emerged from the analyses. Conclusions: This meta-analysis of 15 years of clinical research suggests that antibiotic prophylaxis with a combination of topical and systemic drugs can reduce respiratory tract infections and overall mortality in critically ill patients. This effect is significant and worth while, and it should be considered when practice guidelines are defined. Key messages: Over 40% of patients who need ventilation in intensive care develop respiratory tract infections and about 30% may die in the units If the most effective antibiotic prophylaxis (that is, a protocol combining topical and systemic antibiotics) is used the incidence of respiratory tract infections can be reduced by 65% and total mortality by 20% A regimen of topical antibiotics alone reduces respiratory tract infections but does not influence survival The concern that widespread antibiotic use may lead to resistance cannot be confirmed or ruled out by this review. Trials with different design are probably warranted to handle this question This important effect of antibiotic prophylaxis with a combination of topical and systemic antibiotics on survival should be considered by intensivists when treatment policies are designed