LAUSR

Dear Editor, Two recent reviews that describe, on the one hand, the evidence for antibiotic harm to individual ICU patients [1] and on the other, the evidence for improved patient outcomes associated with the use of topical antibiotic decontamination as prophylaxis against ICU acquired infection [2], are of great interest. Both reviews mention the key role of the gut microbiome as a reservoir for ICU acquired infection. As one review notes, in studying the effects of antibiotics in the ICU is that “..some infections may be caused by pathogens acquired through cross-transmission..” is a key study design consideration [2]. Can these two seemingly contrasting reviews be reconciled? Among studies of various methods of preventing ICU acquired infection, topical antibiotic-based methods (Selective digestive decontamination; SDD) appear superior to various non-antibiotic-based methods. However, there are paradoxical observations among these studies that raise questions as to the mechanism of apparent benefit attributed to the topical antibiotic-based methods. Whilst the evidence for apparent benefit from topical antibiotic prophylaxis is most apparent among studies with randomized (concurrent) control patients, these control groups have incidences of VAP, bacteremia, candidemia [3] and even mortality [4] that are as much as five percentage points higher than expected versus groups from studies of comparable ICU populations. These comparable populations are within either studies where topical antibiotic prophylaxis is not in use or studies that use methods of infection prevention not based on antibiotics or within non-concurrent control groups of studies of topical antibiotics. By contrast, paradoxically, the event rates among intervention groups receiving topical antibiotics are overall similar to these comparable populations. These differences remain robust in meta-regression models of mortality incidence and VAP incidence adjusted for factors such as group mean age, publication year and type of group membership that includes data from groups of > 200 studies of various methods of ICU acquired infection prevention [3]. For example, in a plot versus group mean age, the incidence of mortality among 41 concurrent control groups are mostly above a regression line derived from 34 groups without an intervention. Groups from comparable populations within studies other than topical antibiotics straddle this line. Curiously, the topical antibiotic intervention groups (n = 62) also straddle this line (Fig. 1).