Infection Control & Hospital Epidemiology 0 SE(log[RR])
397
constructed the funnel plots, which are available as supplementary material online.
0.5 Discussion 1 1.5 2 0.01 0.1 1 10 RR 100
Fig. 4. Funnel plot illustrating the risk of overall gram-negative infections with chlorhexidine bathing versus comparator. Dashed line indicates pooled relative risk of 0.89.
the study by Bleasdale et al21 yielded a decreased risk of infection with Klebsiella in patients receiving CHG bathing (RR, 0.53; 95% CI, 0.29–0.93; P = .03).21 Escherichia coli: The meta-analysis of 6 studies (n = 20,770) did
not show a significant reduction in risk of infection with E. coli in patients receivingCHGbathing compared to controls. There was a significant increase in risk of infection with E. coli in patients receiving CHG bathing (RR, 1.74; 95% CI, 1.03–2.92; P = .04) (Fig. 3c). There was no heterogeneity across these studies (I2 = 0%). Influence analysis showed that the exclusion of the studies by Gould et al4 and Boonyasiri et al7 yielded an increase in the risk of E. coli infections in patients receiving CHG bathing [(RR, 1.36; 95% CI, 0.67–2.76; P = .85) and (RR, 1.66; 95% CI, 0.96–2.87; P = .07), respectively] but these increases were not statistically significant. Enterobacter: Our meta-analysis of 5 studies (n = 18,404) did
not show a significant reduction in risk of infection with Enterobacter in patients receiving CHG bathing (RR, 0.75; 95% CI, 0.32–1.75; P = .51) (Fig. 3d). Heterogeneity was moderate across these studies (I2 = 43%). Influence analysis showed that exclusion of the study by Noto et al5 yielded a decrease in the risk of infection with Enterobacter in patients receiving CHG bathing (RR, 0.59; 95% CI, 0.36–0.97; P = .04). Pseudomonas: The meta-analysis of 7 studies (n = 24,697)
did not show a significant reduction in risk of infection with Pseudomonas in patients receiving CHG bathing (RR, 0.92; 95% CI, 0.61–1.4; P = .71) (Fig. 3e). There was no heterogeneity across these studies (I2 = 0%). An influence analysis showed that no particular study affected the pooled effect size.
Publication bias
Weevaluated publication bias over all
GNIs.Afunnel plot of the 12 included studies is shown in Figure 4. On visual inspection, the funnel plot appears symmetric. As per Egger’s method, there was no evidence of publication bias (intercept = 0.44; t = 0.37; 1-tailed P = .36). Adjustment using Duval and Tweedie’s trim- and-fill procedure resulted in a similar imputed RR of 0.88 (95% CI, 0.71–1.07). For each of the specific gram-negative bacteria, we did not formally assess publication bias because the number of included studies was <10. Egger’s linear regression test is unreliable when there are <10 included studies. However, we
In this systematic review and meta-analysis of 15 studies with 34,895 ICU patients, daily CHG bathing was not associated with reduced risk of infection with gram-negative bacteria. Subgroup analysis demonstrated that daily CHG bathing did not significantly reduce the risk of gram-negative infections caused by Acinetobacter, E. coli, Klebsiella, Enterobacter,or Pseudomonas spp. Daily CHG bathing has been shown to be effective at reducing
the risk and transmission of gram-positive infections, including MRSA and VRE.2–4 Our meta-analysis suggests that this interven- tion may not be effective at reducing the risk of gram-negative infections in the ICU. Chlorhexidine is a cationic biguanide that has broad-spectrum antimicrobial activity attributable to disrup- tion of cytoplasmic membranes, with higher in vitro activity against gram-positive bacteria than gram-negative bacteria.29 Although several studies have demonstrated that gram-negative bacteria have a higher minimum inhibitory concentration (MIC) for CHG than gram-positive bacteria, the amount of CHGapplied to the skin is many fold higher than the MIC for both gram-negative and gram-positive bacteria.30,31 However, the effec- tiveness of CHG application varies based on hospital antiseptic practices (ie, frequency, area of application, method of applica- tion), is often identified as suboptimal, and can lead to relatively low concentrations of CHG on skin that may be insufficient to inhibit gram-negative bacteria.32 Furthermore, most of the gram-negative bacilli collected from the skin in 1 randomized con- trolled trial were from the perianal area, which suggests the gram- negative bacteria might have shed from the gastrointestinal tract. Although daily CHG bathing can help reduce skin contamination originating from the gut, it is unlikely that they affect the coloni- zation of the gastrointestinal tract.7 In ICUs, a substantial propor- tion of infections due to gram-negative bacilli may attributable to translocation of organisms from the intestinal tract.8 Our subgroup analyses of individual gram-negative bacteria
also demonstrated that CHG bathing did not significantly reduce the risk of gram-negative bacterial infections. On the contrary, the risk of infections with E. coli was significantly higher in patients receiving CHG bathing group compared to controls. However, because of the smaller number of included studies, the results of the subgroup analyses should be interpreted with caution. With a small number of included studies, the larger studies among them can be influential, as was demonstrated in our influence analyses. Also, not all studies were designed specifically to evaluate the effect of CHG bathing on the rate of gram-negative infections. The findings of this meta-analysis are in agreement with a prior meta-analysis of 4 studies (sample size = 22,850 patients). Afonso et al13 concluded, following secondary subgroup analyses of 4 stud- ies, that there was no reduction in gram-negative infection with CHG bathing; however, the primary objective of the study was to assess the effect of CHG on CLABSIs and other hospital- acquired bloodstream infections.13 Other meta-analyses have focused on the impact of CHG on MRSA and VRE, or general HAIs, without directly evaluating the impact of CHG on gram- negative bacteria.10–12 Our meta-analysis, therefore, built upon prior meta-analyses to further examine the effect of CHG bathing on gram-negative bacteria in an ICU setting. The goal of our study was not only to combine the statistical analyses of observational
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