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studies but also to systematically assess the impact ofCHGbathing on gram-negative infections and on infection with specific gram- negative bacteria, as well as to assess heterogeneity across studies. Themeta-analysis of observational studies is challenging because it includes greater focus on study quality and ensuring low hetero- geneity across included studies. The strengths of our study include the following: our findings are consistent with previous studies; our study included a significantly large population of patients; we uti- lized the NOS scale for quality analysis; and we strictly followed PRISMA guidelines for systematic reviews (Supplemental Table 2 online). Our study has several limitations. First, the studies in our meta-
analysis vary in terms of study design, diagnostic microbiologic cultures used to detect infection, and follow-up period. There was significant variability in the choice and definition of study outcome, including but not limited to bloodstream infections, ventilator-associated pneumonia, and urinary tract infections. The setting of included studies also varied, ranging from medical ICUs to bone marrow transplant units. Data regarding these variations were largely insufficient to permit subgroup analysis beyond looking at specific gram-negative bacteria. Also, we used the traditional methods for conducting our meta-analysis, although some have recommended using the Bayesian method of meta-analysis when the included studies are either small or the relative risks are close to 0 or 1.33 Second, although a relatively limited number of studies were included in our meta-analysis, the included studies were the product of a comprehensive literature search and had a large sample size of almost 35,000 subjects. Third, several of the included studies were observational or quasi-experimental and, consequently, were subject to residual confounding. Also, we excluded studies that focused on coloniza- tion acquisition of gram-negative
pathogens.Afourth limitation of this meta-analysis is that it employed a random-effect model, which may place greater emphasis on smaller studies with lower quality data, compared to a fixed-effects model. Finally, as many of the included studies were observational or quasi-experimental, this meta-analysis did not establish causality with regard to CHG bathing as an intervention. Multiple institutions have implemented CHG bundles as part
of their efforts to reduce the infections and transmission of multidrug-resistant gram-positive and gram-negative bacteria. However, it appears that there are insufficient data and evidence to support these practices for gram-negative bacteria. The current evidence may be skewed because very few studies have reported the rates of compliance with CHG bathing in their ICUs, and other studies have reported no detectable CHG on the skin of patients after CHG bathing. Therefore, there is an urgent need for studies specifically designed to evaluate the impact ofCHGbathing on the rates of gram-negative infections while also monitoring the rate of compliance with CHG bathing procedures and the skin levels of CHG after bathing. Future studies should explore alternative approaches for the prevention of infection with gram-negative organisms in an ICU setting.
Supplementary material. To view supplementary material for this article, please visit
https://doi.org/10.1017/ice.2019.20.
Acknowledgments.
Financial support. No financial support was provided relevant to this study. J.A.O. would like to acknowledge support from the National Institute for Health Research Health Protection Research Unit in Healthcare-Associated Infections and Antimicrobial Resistance at Imperial College London in partnership with
Aditi Patel et al
Public Health England, and the Imperial College Healthcare Trust NIHR Biomedical Research Centre.
Conflicts of interest. Abhishek Deshpande has received research support from Clorox not related to this study. Curtis J. Donskey has received research support from Clorox,GOJO, PDI, Avery Dennison, and Ecolab unrelated to this study. Jonathan A. Otter is a consultant to Gama Healthcare and Pfizer. Priyaleela Thota is a consultant for Vancive Medical Technologies. All other authors report no conflicts of interest relevant to this article.
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