Effectiveness of antibiotic prophylaxis in critically ill adult patients: systematic review of randomised controlled trials

BMJ 1998;316:1275-1285 ( 25 April )

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Effectiveness of antibiotic prophylaxis in critically ill adult patients: systematic review of randomised controlled trials

Roberto D'Amico, research fellow, ^a Silvia Pifferi, research fellow, ^b Cinzia Leonetti, research fellow, ^b Valter Torri, chief of biometry unit, ^a Angelo Tinazzi, computer scientist, ^a Alessandro Liberati, head, ^a fn behalf of the study investigators.

^a Mario Negri Institute for Pharmacological Research, 20157 Milan, Italy, ^b Maggiore Ospedale IRCCS, 20122 Milan

Correspondence to: Dr A Liberati, Italian Cochrane Centre, Laboratory of Health Services Research, Mario Negri Institute, Via Eritrea 62, 20157 Milan, Italy

Cochrane{at}irfmn.mnegri.it

Objective: To determine whether antibiotic prophylaxis reduces respiratory tract infections and overall mortality inunselected critically ill adult patients.
Design: Meta-analysis of randomised controlled trials from 1984 and 1996 that compared different forms of antibioticprophylaxis used to reduce respiratory tract infections and mortalitywith aggregate data and, in a subset of trials, data from individualpatients.
Subjects: Unselected critically ill adult patients; 5727 patients for aggregate data meta-analysis, 4343 for confirmatorymeta-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 andtopical preparation with or without a systemic antibiotic versusa systemic agent or placebo. Estimates from aggregate data meta-analysisof 16 trials (3361 patients) that tested combined treatment indicateda 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 wouldneed to be treated to prevent one infection and one death, respectively.Similar analysis of 17 trials (2366 patients) that tested onlytopical 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 patientsyielded similar results. No significant differences in treatmenteffect 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 combinationof topical and systemic drugs can reduce respiratory tract infectionsand overall mortality in critically ill patients. This effectis significant and worth while, and it should be considered whenpractice 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

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