Paradoxical Acinetobacter-associated ventilator-associated pneumonia incidence rates within prevention studies using respiratory tract applications of topical polymyxin: benchmarking the evidence base

Abstract

Regimens containing topical polymyxin appear to be more effective in preventing ventilator-associated pneumonia (VAP) than other methods. To benchmark the incidence rates of Acinetobacter-associated VAP (AAVAP) within component (control and intervention) groups from concurrent controlled studies of polymyxin compared with studies of various VAP prevention methods other than polymyxin (non-polymyxin studies). An AAVAP benchmark was derived using data from 77 observational groups without any VAP prevention method under study. Data from 41 non-polymyxin studies provided additional points of reference. The benchmarking was undertaken by meta-regression using generalized estimating equation methods. Within 20 studies of topical polymyxin, the mean AAVAP was 4.6% [95% confidence interval (CI) 3.0-6.9] and 3.7% (95% CI 2.0-5.3) for control and intervention groups, respectively. In contrast, the AAVAP benchmark was 1.5% (95% CI 1.2-2.0). In the AAVAP meta-regression model, group origin from a trauma intensive care unit (+0.55;+0.16 to+0.94, P=0.006) or membership of a polymyxin control group (+0.64;+0.21 to+1.31, P=0.023), but not membership of a polymyxin intervention group (+0.24; -0.37 to+0.84, P=0.45), were significant positive correlates. The mean incidence of AAVAP within the control groups of studies of topical polymyxin is more than double the benchmark, whereas the incidence rates within the groups of non-polymyxin studies and, paradoxically, polymyxin intervention groups are more similar to the benchmark. These incidence rates, which are paradoxical in the context of an apparent effect against VAP within controlled trials of topical polymyxin-based interventions, force a re-appraisal.