The Perfidious Effect of Topical Placebo: Calibration of Staphylococcus aureus Ventilator-Associated Pneumonia Incidence within Selective Digestive Decontamination Studies versus the Broader Evidence Base

Abstract

ABSTRACTAmong various methods for preventing ventilator-associated pneumonia (VAP), the evidence base for selective digestive decontamination (SDD) appears most compelling. However, the extent ofStaphylococcus aureusemergence with SDD use remains uncertain. Groups from 37 observational studies and component (control and intervention) groups from 58 studies of SDD and other methods of VAP prevention were sourced exclusively from 10 systematic reviews.S. aureusas a proportion of VAP isolates (S. aureusisolate proportion [S. aureusIP]) among component groups was calibrated versus that among observational groups (the benchmark). The influence of topical placebo used for blinding purposes and other group-level factors was estimated using generalized estimating equation methods (GEE). The meanS. aureusIP is 22% (95% confidence interval [CI], 19 to 25) for 37 observational groups versus 32% (24 to 41) and 20% (15 to 25) for 22 control groups from the SDD evidence base which did versus did not receive topical placebo, respectively. In GEE models including all 148 observational and component groups, membership of a control (P= 0.03) or intervention (P< 0.001) group of an SDD study that used topical placebo was associated with higherS. aureusIP, whereas, in contrast, membership of these groups was without effect onPseudomonas aeruginosa. Topical placebo is implicated as a vehicle for selective cross-infection withS. aureuswithin the specific context of the SDD evidence base. This effect of topical placebo is perfidious; it could contribute to the higher VAP incidence and inflate the apparent “effectiveness” of SDD. The SDD evidence base requires reappraisal.