Infection Control & Hospital Epidemiology
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Fig. 1. Flow diagram of study selection process. Eligibility criteria
Two investigators (A.P. and P.P.) independently searched the literature in a systematic way using the following inclusion cri- teria: individual or cluster randomized controlled trials and quasi-experimental studies, both published and unpublished, that evaluated the efficacy of daily bathing withCHGversus soap and water or standard care to prevent healthcare-associated infections in ICUs and non-ICUs. The following exclusion criteria were applied: studies using CHG bathing perioperatively for the purposes of reducing surgical site infections, studies evaluating colonization rates, studies presenting data based on events and not the number of actual patients, and pediatric studies. Review articles and editorials were not included in the search list. The search was performed inNovember 2015 and was updated
in July 2018. The following databases were searched from inception to July 2018: PubMed, EMBASE, Web of Science, and Scopus. We used the terms “chlorhexidine bathing” as the search term in all 4 databases without any language restrictions. The electronic PubMed search strategy is available in the supplemental appendix online. Reference lists of all included studies and previous meta- analyses on similar topics were manually searched for additional publications.
Study selection
A list of retrieved articles that met the inclusion criteria was reviewed by 2 investigators independently (A.P. and P.P.). Any dis- agreement about a particular study was resolved by consensus with a third investigator (A. Deshpande). The PRISMA flow diagram was used to present the study selection process through its different phases (Fig. 1).
Data extraction
Data were extracted by 2 investigators independently (A.P. and P.P.) using a standard data extraction form. The data collected
included year of publication, country of origin, study design, study population, duration, study setting, intervention, comparator, cointervention, and patient demographics. Information relating to specific gram-negative etiology was also collected where avail- able. Any disagreement was resolved by consensus with a third investigator (A. Deshpande). Study authors were contacted if rel- evant information was not available for a particular study. The primary outcome of interest was the risk of developing gram-negative infections in patients undergoing daily bathing with and without CHG. Secondary outcomes of interest included the risk of developing infections related to specific gram-negative bacteria.
Quality assessment
We used the Newcastle-Ottawa scale (NOS) for determining the quality of the observational studies.15 The NOS uses 2 different tools for case-control and cohort studies, and it consists of 3 parameters of quality: selection, comparability, and outcome assessment. A NOS score ≥7 indicates a high-quality study. We assessed the risk of bias of the randomized controlled trials (RCTs) according to the Cochrane Risk of Bias tool. The tool assesses 7 specific domains: (1) random sequence generation, (2) allocation concealment, (3) blinding of participants and personnel, (4) blinding of outcome assessment, (5) incomplete outcome data, (6) selective outcome reporting, and (7) other issues. For eachRCT, each item was described as low risk of bias, high risk of bias, or unclear risk of bias by 2 independent investigators (A. Dunn and A. Deshpande).
Data synthesis and analysis
For each of the studies, we calculated the risk ratio for developing gram-negative infections (primary and secondary outcomes) and their 95% confidence intervals (CIs). The Mantel-Haenszel method with random-effects modeling was then used to calculate the pooled risk ratios (RRs) and their 95% CIs. We evaluated
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