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Fig. 2. Forest plot illustrating the risk of overall gram-negative infections (GNIs) with chlorhexidine (CHG) bathing versus comparator. The vertical line corresponds to the no difference point between the 2 groups. Squares, the size of which indicates the proportion of information given by each study, correspond to risk ratios. Horizontal lines represent the 95% confidence intervals. The diamond indicates the pooled relative risk ratios. Note. df, degrees of freedom; M-H, Mantel-Haenszel.
statistical heterogeneity using the Cochran χ2 test and the I2 statistic.16 I2 values of 40%–60% were considered to represent a moderate level of heterogeneity.17AP value<.10 for χ2 was defined as indicating the presence of heterogeneity. We utilized Review Manager software (RevMan, version 5.3 for Windows, Oxford, UK; The Cochrane Collaboration, 2008) and Comprehensive Meta-Analysis version 2.0 software (Biostat, Englewood, NJ) for all statistical analyses.
Assessment of risk of bias
To evaluate publication bias, we generated funnel plots and used Egger’s regression asymmetry test. Where asymmetry was detected, we assessed the potential impact of publication bias using the Duval and Tweedie nonparametric “trim and fill” method.18,19 We performed influence analyses to determine whether any single study had a disproportionate impact on the pooled estimates and heterogeneity (analyses was repeatedomitting one study at a time). To assess the influence of time (temporal trend) on the effect esti- mate, we also performed a cumulative meta-analysis.
Results Study characteristics
Our search identified 820 publications (Fig. 1). After removing duplicates and screening study titles, 42 articles were selected based on relevance to the study topic. After screening the abstracts of these potentially relevant articles based on their relevance, 26 were selected for full-text review (Fig. 1). In total, 15 articles were included in the systematic review. The reasons for exclusion of the remaining 11 articles are listed in Figure 1. Of the 15 included studies, 3 studies exclusively examined the effect of CHG bathing on risk of infection with Acinetobacter baumanii; the other 12 included studies examined the effect of CHG bathing on risk of infection with all gram-negative organisms. Therefore, 12 studies were meta-analyzed for the primary outcome of interest and the number of included studies varied for the secondary outcomes related to specific gram-negative bacteria. Table 1 summarizes basic characteristics of the included studies. A total of 34,895 patients (range, 38–9,340) were included in the meta-analysis. Amongthe included studies, 7 were prospective cohorts,6,21,20,22,25,26,28
4 were randomized controlled trials,3,5,7,8 and 4 were retrospective cohorts.4,23,24,27
Quality assessment
Based on theNOSscale, 8 of 11 included observational studies were deemed high quality, and the remaining 3 were deemed moderate quality (Supplemental Table 1 online). All included studies clearly identified the study population (cases and controls). However, there was variation in the type of culture used for assessment of the study outcome (Table 1). Studies also varied in whether they controlled for variables including age and sex (Supplemental Table 1 online). The risk of bias was lowformost items assessed by the Cochrane
risk of bias tool (Supplemental Table 2 online). When no specific descriptions were available, we chose the answer of unclear risk.
Effect of CHG bathing on risk of infection with gram-negative organisms
Overall, our meta-analysis of 12 studies (n = 30,234) to assess the impact ofCHGbathing did not showa significant reduction in risk of gram-negative infections (GNI) in patients receiving CHG bathing compared to control patients (RR, 0.89; 95% CI, 0.73–1.08; P = .24) (Fig. 2). Heterogeneity was moderate across these studies (I2=50%). Influence analysis (ie, excluding 1 study at a time) showed that no particular study affected the pooled effect size. Cumulative meta-analysis showed that the RRs were consistent over time. A subanalysis of high-quality observational studies and RCTs, did not show a significant reduction in risk ofGNI in patients receiving CHG bathing compared to control patients (RR, 0.90; 95% CI, 0.74–1.09; P = .27). Acinetobacter: Meta-analysis of 8 studies (n = 16,731) did
not show a significant reduction in the risk of infection with Acinetobacter in patients receivingCHGbathing compared to con- trols (RR, 0.67; 95% CI, 0.21–2.18; P=.51) (Fig. 3a). Heterogeneity was high across these studies (I2 = 95%). An influence analysis showed that no particular study affected the pooled effect size. Klebsiella: Our meta-analysis of 6 studies (n = 21,757) did not
show a significant reduction in risk of infection with Klebsiella in patients receiving CHG bathing compared to controls (RR, 0.57; 95% CI, 0.31–1.04; P=.07) (Fig. 3b). Heterogeneity was low across these studies (I2 = 7%). Influence analysis showed that excluding
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