Daily Chlorhexidine Bathing for the Prevention of Nosocomial Infections in Critically Ill Patients (CLEAN-IT): a multicentre, cluster-randomised, crossover trial.

Background: Critically ill patients are at risk of nosocomial infections, acquisition of multidrug-resistant pathogens, and substantial antimicrobial consumption. We assessed whether bathing with chlorhexidine reduces these outcomes compared to standard practices. Methods: We conducted an open-label, cluster-randomised crossover trial in 22 Brazilian intensive care units comparing daily chlorhexidine bathing versus soap and water bathing (control). Centres were randomised to 3- or 6-months chlorhexidine or control periods, separated by a 1-month washout. Primary outcome was nosocomial infection rate (central line-associated bloodstream infections, catheter-associated urinary tract infections, and ventilator-associated pneumonia) during ICU stay. Secondary outcomes included specific nosocomial infections incidence, multi-drug resistant cultures, antibiotic use, length of stay, and mortality. This completed trial is registered at ClinicalTrials.gov, NCT05485051. Findings: From August 1st, 2022 to December 31, 2023, we included 15,935 patients (8247 chlorhexidine and 7688 control group). Mean age was 64·4 years (SD 17·3) in the chlorhexidine group [4315 (52·3%) male] and 64·2 years (SD 17·4) in the control group [4035 (52·5%) male]. A total of 201 nosocomial infections occurred in the chlorhexidine group, compared to 165 in the control group. There was no statistically significant difference in the overall nosocomial infections rate between groups [3·99 per 1000 patient-days in the chlorhexidine group and 3·45 per 1000 patient-days in the control group (rate-ratio, 1·09; 95% CI 0·95-1·25; p = 0·22)]. Patients in the chlorhexidine group had lower rates of multi-drug resistant cultures compared to the control group (14·42 vs. 20·13 per 1000 patient-days, rate-ratio, 0·73; 95% CI 0·59-0·91; p = 0·0092). Although overall antimicrobial consumption defined by WHO's DDD did not differ between groups (rate-ratio, 0·91; 95% CI 0·80-1·03; p = 0·14), there was a statistically significant difference in the consumption of antimicrobials in the Reserve group of WHO's AWaRe classification (rate-ratio, 0·73; 95% CI 0·59-0·90; p = 0·0071) in the chlorhexidine group. This reduction was not associated with higher mortality. Interpretation: Chlorhexidine bathing did not reduce the incidence of nosocomial infections in a general ICU population, but contributed to lower rates of multi-drug resistant pathogen isolation, and lower use of Reserve antimicrobials, potentially leading to a qualitative modification of antimicrobial use. Funding: This study was funded by the Brazilian Health Ministry through the Programa de Apoio ao Desenvolvimento Institucional do Sistema Único de Saúde (PROADI-SUS).