Estimating the herd effects of antimicrobial prevention interventions on ventilator-associated pneumonia within ICU populations: a cluster randomized trial emulation using data from Cochrane reviews.

Abstract

Background The herd effects of antimicrobial interventions used to prevent ICU-acquired infections are unknown. The objective here was to estimate these herd effects within a single three-tiered cluster randomized trial (CRT) emulated using ventilator-associated pneumonia (VAP) data from randomized concurrent control trials (RCCTs) abstracted within Cochrane reviews. Methods Control and intervention group data derived from 13 Cochrane reviews of 72 RCCTs of antibiotic (Tier 3) and antiseptic (Tier 2) decontamination versus 109 RCCTs of various non-decontamination (Tier 1, serving as benchmark) VAP prevention interventions were arranged as a three-tiered CRT. The direct and indirect (herd) effects of Tiers 2 and 3 each versus Tier 1 interventions were obtained using estimators derived in meta-regression models. Results Benchmark (Tier 1) VAP incidences derived for control and intervention groups from non-decontamination RCCTs were 23.3 (95% CI: 20.6–26.1; n = 111) and 19.2 (95% CI: 16.8–21.8; n = 112), respectively. The mean VAP incidences for antibiotic and antiseptic decontamination control groups were 5% to 15% higher than the control group benchmark. The direct effects of antibiotic and antiseptic interventions versus Tier 1 benchmarks (ORs) were 0.77 (95% CI: 0.55–1.09) and 0.97 (95% CI: 0.71–1.33) whereas the indirect effects were 2.17 (95% CI: 1.56–3.03) and 1.38 (95% CI: 1.0–1.91), respectively. Conclusions Indirect (herd) effects from antimicrobial interventions, although inapparent within individual RCCTs, are strong. These effects on control group VAP incidences, which spuriously conflate the appearance of benefit, constitute herd peril.