Daily Chlorhexidine Bathing in the ICU: Re-evaluating Infection Prevention and Antimicrobial Stewardship through the CLEAN-IT Trial

Highlights

• The CLEAN-IT trial, involving 15,935 patients across 22 ICUs, found no significant reduction in the primary composite rate of nosocomial infections (CLABSI, CAUTI, VAP) with daily chlorhexidine (CHG) bathing compared to standard soap and water.
• CHG bathing was associated with a statistically significant 27% reduction in the isolation of multi-drug resistant (MDR) pathogens from clinical cultures.
• Consumption of ‘Reserve’ category antibiotics (WHO AWaRe classification) was significantly lower (RR 0.73) in the CHG group, suggesting a profound impact on antimicrobial stewardship.
• The trial highlights a shift in the perceived utility of CHG bathing from broad infection prevention to a targeted strategy for reducing MDR colonization and qualitative antibiotic use.

Background

Healthcare-associated infections (HAIs) remain a primary driver of morbidity, mortality, and healthcare costs in intensive care units (ICUs) globally. For over a decade, daily bathing with chlorhexidine gluconate (CHG), an antiseptic with broad-spectrum activity against Gram-positive and many Gram-negative organisms, has been a cornerstone of infection prevention bundles. The rationale is based on the reduction of the skin microbiome’s bioburden, thereby decreasing the risk of cross-transmission and endogenous contamination of invasive devices such as central venous catheters and urinary catheters.

Early trials and observational studies suggested substantial benefits, particularly in reducing central line-associated bloodstream infections (CLABSIs) and methicillin-resistant Staphylococcus aureus (MRSA) acquisition. However, as ICU practices have evolved with the widespread implementation of specialized bundles (e.g., the ‘ventilator bundle’ or ‘insertion bundles’), the marginal benefit of universal CHG bathing in general ICU populations has come under scrutiny. Furthermore, the rising threat of antimicrobial resistance and reports of reduced susceptibility to CHG itself necessitate a rigorous re-evaluation of its clinical utility in large-scale, real-world settings.

Key Content

Chronological Evolution of Evidence for CHG Bathing

The evidence base for CHG bathing has shifted significantly over the last 15 years. Initial landmark studies, such as the cluster-randomized trial by Climo et al. (2013), demonstrated a 23% reduction in HAIs and a significant decrease in MRSA and Vancomycin-resistant Enterococcus (VRE) acquisitions. This was followed by the REDUCE MRSA trial (Huang et al., 2013), which showed that universal decolonization (CHG bathing plus intranasal mupirocin) was more effective than targeted decolonization or screening/isolation in reducing MRSA clinical isolates and all-cause bloodstream infections.

However, subsequent studies in different geographic and clinical contexts began to show mixed results. For instance, the MORDOR trial and several European studies indicated that in ICUs with already low baseline infection rates or high adherence to standard care bundles, the additional benefit of CHG bathing was negligible. This led to the design of the CLEAN-IT trial, intended to provide high-quality evidence in a resource-diverse setting like Brazil.

The CLEAN-IT Trial: Methodological Rigor and Primary Findings

The CLEAN-IT trial (Tomazini et al., 2026) utilized a multicentre, cluster-randomised crossover design—a robust methodology for evaluating unit-wide interventions. Spanning 22 Brazilian ICUs and including nearly 16,000 patients, it is one of the largest trials to date addressing this topic. Patients were subjected to daily 2% CHG bathing or standard soap and water, with treatment periods lasting 3 to 6 months separated by a washout period.

Primary Outcome: The study reported 3.99 nosocomial infections per 1000 patient-days in the CHG group versus 3.45 in the control group. The rate-ratio (RR) of 1.09 (95% CI 0.95–1.25; p = 0.22) confirms that CHG bathing did not significantly lower the incidence of the composite endpoint (CLABSI, CAUTI, and VAP). This finding suggests that in the modern ICU environment, where device-care bundles are standard, the antiseptic effect of CHG on the skin may not translate into a reduction of deep-seated or device-related infections as once hypothesized.

Secondary Outcomes: Impact on MDR and Antimicrobial Use

Despite the negative primary outcome, the secondary findings of CLEAN-IT offer critical insights for clinicians:

• MDR Pathogen Reduction: A significant reduction in MDR cultures (14.42 vs. 20.13 per 1000 patient-days; RR 0.73) suggests that CHG remains effective at reducing the environmental and skin presence of highly resistant organisms. This has major implications for infection control and the prevention of ICU outbreaks.
• Antibiotic Stewardship: Most notably, the trial observed a 27% reduction in the use of ‘Reserve’ group antimicrobials (e.g., polymyxins, ceftazidime-avibactam). These are drugs of last resort, often used empirically when MDR colonization is suspected or confirmed. By reducing MDR isolation, CHG bathing may indirectly prevent the ‘escalation’ of antibiotic therapy, even if it does not prevent the initial infection.

Expert Commentary

The CLEAN-IT trial represents a turning point in our understanding of antiseptic decolonization. The lack of effect on the primary infection rate is likely multifactorial. First, the pathogenesis of VAP is largely related to micro-aspiration of oropharyngeal secretions rather than skin flora, making it an insensitive target for CHG bathing. Second, the increasing quality of baseline ICU care (standard soap bathing, hand hygiene, and sterile technique) may have reached a threshold where the antiseptic superiority of CHG is marginal.

However, the reduction in MDR cultures and ‘Reserve’ antibiotic use is a compelling finding. It suggests that CHG bathing acts as a tool for qualitative modification of patient care. In an era of escalating resistance, any intervention that reduces the selective pressure of broad-spectrum antibiotics is highly valuable. Clinicians should view CHG bathing not as a singular prophylactic against all infections, but as a specific strategy to curb the spread of MDR pathogens and support stewardship programs.

One limitation and point of controversy is the potential for CHG resistance. While CLEAN-IT did not report on qacA/B gene prevalence or MIC shifts, the broad use of CHG in 22 units over a year warrants long-term surveillance to ensure that we are not trading antibiotic resistance for antiseptic resistance.

Conclusion

The CLEAN-IT trial demonstrates that daily chlorhexidine bathing is not a panacea for nosocomial infections in a general ICU population. However, its significant role in reducing the burden of multi-drug resistant pathogens and the subsequent need for ‘last-resort’ antibiotics provides a strong rationale for its continued, though perhaps more targeted, use in high-risk environments. Future research should focus on cost-benefit analyses of CHG bathing in low- versus high-prevalence MDR settings and investigate the long-term ecological impact of universal antiseptic use.

References

• Tomazini BM, et al. Daily Chlorhexidine Bathing for the Prevention of Nosocomial Infections in Critically Ill Patients (CLEAN-IT): a multicentre, cluster-randomised, crossover trial. Lancet Reg Health Am. 2026;56:101400. PMID: 41732706.
• Climo MW, et al. Effect of daily chlorhexidine bathing on hospital-acquired infection. N Engl J Med. 2013;368(6):533-542. PMID: 23389196.
• Huang SS, et al. Targeted versus universal decolonization to prevent ICU infection. N Engl J Med. 2013;368(24):2255-2265. PMID: 23718152.
• Musuuza JS, et al. Effectiveness of chlorhexidine bathing to reduce catheter-associated urinary tract infections: a systematic review and meta-analysis. J Hosp Infect. 2019;103(1):19-26. PMID: 30851336.