Objective: At least 7 meta-analyses (MA) have been published since 1991 on
the effectiveness of antibiotic prophylaxis in Intensive care units (ICU) p
atients, but controversy still remains about the overall effectiveness and
risk-benefits profile of the treatment. This paper aims to summarise availa
ble data on effectiveness and discuss reasons why the controversy is still
open and possible directions for future research.
Design: Review of available published MA on the effectiveness of various re
gimens of antibiotic prophylaxis with particular emphasis on the results of
the individual patient data analysis published in 1998.
Setting: MA or randomised control trials (RCTs) published and unpublished,
conducted anywhere in the world.
Patients and participants: Unselected adult ICU populations included in stu
dies, published and unpublished, comparing different forms of antibiotic pr
ophylaxis.
Main outcome measure: Respiratory tract infections (RTIs) - however defined
in individual studies - and total mortality.
Data sources: General information from the 7 MAs published between 1991 and
1999 and detailed information from the MA published in the British Medical
Journal in 1998 that reported data on 5727 patients enrolled in 33 RCTs; a
ccess to individual patients data could be obtained from 25 of 33 RCTs and
allowed a confirmatory individual patient MA on 4343 patients.
Results: Pooled estimates from 16 RCTs (including 3361 patients) testing th
e effect of the topical and systemic antibiotic combination indicates a sig
nificant reduction of both RTIs (OR = 0.35, 95 % CI = 0.29-0.41) and total
mortality (OR = 0.80, 95 % CI = 0.69-0.93). Five and 23 patients need to be
treated to prevent one infection and one death, respectively, using this t
reatment. Pooled data from the 17 RCTs (including 2366 patients) testing th
e effect of a regimen based on topical antimicrobials indicated a statistic
ally significant reduction in RTIs (OR = 0.57, 95 % CI = 0.46-0.69) but not
in total mortality (OR = 1.01; 95 % CI = 0.84-1.22). Individual patient da
ta analyses confirmed these results.
Conclusions: After over 30 RCTs and seven MAs, there is strong, evidence th
at antibiotic prophylaxis can reduce both RTIs and total mortality in ICUs
patients in a statistically and clinically significant way. Concerns about
the possible occurrence of antimicrobial resistance are not supported by av
ailable data but cannot, at the same time, be ruled out due to methodologic
inadequacies of the studies carried out so far. Whether new trials are nee
ded, and how they should be designed to answer the question of the potentia
l for antibiotic resistance following widespread use of the treatment, are
now the main issues to be settled. Convening an international panel of clin
ical experts and methodologists could be appropriate, in order to explore t
he best way to resolve the controversy that seems to be preventing the wide
spread use of a treatment that the best analysis of available data now indi
cates is effective.