Effect of Daily Chlorhexidine Bathing and Antibiotic/PPI Stewardship on Prevention of CPE Transmission and Infection

Not Applicable

• Conditions: Carbapenemase-Producing Enterobacteriaceae (CPE); Healthcare-Associated Infections (HAIs)

• Registration Number: NCT07039955
• Lead Sponsor: Chuncheon Sacred Heart Hospital

Brief Summary

This multicenter, cluster-randomized crossover trial aims to evaluate the effectiveness and safety of a bundled intervention-including daily chlorhexidine bathing and targeted antimicrobial and proton pump inhibitor (PPI) stewardship-for preventing colonization and infection caused by carbapenemase-producing Enterobacteriaceae (CPE) in intensive care units (ICUs) across three university-affiliated hospitals in South Korea.

Each hospital will include two ICUs, randomized to either the intervention or control group for six months, followed by a crossover. The intervention group will receive daily bathing using no-rinse, 4% chlorhexidine gluconate (CHG)-impregnated washcloths along with antimicrobial and PPI stewardship focused on reducing unnecessary carbapenem and PPI use. The control group will receive standard bathing without chlorhexidine, while receiving the same stewardship interventions as the intervention group.

Primary outcomes include the incidence and prevalence of CPE colonization and CPE-attributable healthcare-associated infections such as bloodstream infections, hospital-acquired pneumonia, and urinary tract infections. Secondary outcomes include evaluation of residual CHG skin concentrations, comparison with CHG minimum inhibitory concentrations (MICs) of CPE isolates, impact of feedback on adherence to bathing protocols, and assessment of adverse skin reactions to CHG bathing.

Findings from this study are expected to provide evidence-based guidance on the effectiveness and feasibility of combining daily chlorhexidine bathing with no-rinse, 4% CHG-impregnated washcloths and stewardship interventions to control the spread of CPE in high-risk healthcare settings.

Detailed Description

Carbapenemase-producing Enterobacteriaceae (CPE) are a critical public health threat, particularly in healthcare settings where vulnerable patients are at increased risk of colonization and infection. In South Korea, the number of reported CPE cases has increased sharply in recent years, necessitating the implementation of high-impact, evidence-based strategies for prevention and control.

This multicenter, cluster-randomized crossover trial is being conducted in six intensive care units (ICUs) across three university-affiliated hospitals in South Korea. The primary aim of the study is to evaluate the effectiveness and safety of a bundled intervention consisting of daily chlorhexidine bathing and targeted antimicrobial and proton pump inhibitor (PPI) stewardship in reducing CPE colonization and infection.

Each participating hospital will contribute two ICUs. One ICU will initially serve as the intervention unit and the other as the control unit for six months, after which the roles will be crossed over for an additional six months. The intervention group will receive daily bathing using no-rinse, 4% chlorhexidine gluconate (CHG)-impregnated washcloths, along with antimicrobial and PPI stewardship interventions focused on reducing unnecessary use of carbapenems and PPIs. The control group will receive standard bathing without chlorhexidine, while receiving the same stewardship measures as the intervention group.

Primary outcomes include the incidence and prevalence of CPE colonization and CPE-attributable healthcare-associated infections (HAIs), such as bloodstream infections, hospital-acquired pneumonia, and urinary tract infections. Surveillance cultures will be obtained per institutional protocols and national guidelines, including rectal swabs at ICU admission and weekly thereafter.

Secondary outcomes include:

1. Assessment of residual CHG skin concentrations at 3-month intervals using standardized skin swabs and comparison of these concentrations with the minimum inhibitory concentrations (MICs) of CPE isolates obtained from clinical and surveillance cultures to evaluate the adequacy of chlorhexidine exposure.

2. Evaluation of adherence to CHG bathing protocols through quarterly feedback of CHG skin concentration results to ICU staff.

3. Assessment of adverse skin reactions associated with CHG bathing to evaluate its safety in critically ill patients.

Skin swab samples will be obtained from the neck, axilla, and groin using a standardized technique. CHG concentrations will be analyzed via a semiquantitative colorimetric assay. CPE isolates will undergo broth microdilution testing to determine the MICs of CHG, following modified Clinical and Laboratory Standards Institute (CLSI) guidelines. CPE isolates will undergo broth microdilution MIC testing based on modified CLSI guidelines.

In parallel, antimicrobial and PPI utilization will be monitored using antibiotic use density (AUD) metrics. Stewardship interventions will focus on minimizing unnecessary use of carbapenems and PPIs, particularly for ventilator-associated pneumonia prophylaxis, and promoting use of alternatives where appropriate. Monthly trends in AUDs will be tracked for carbapenems, ampicillin/sulbactam, ceftazidime/avibactam, cefiderocol, colistin, and other key antibiotics, as well as PPIs and H2 blockers.

This study is designed to provide high-quality evidence on the effectiveness and feasibility of bundled interventions for the prevention of CPE transmission and infection in high-risk ICU settings. Findings from this trial may inform national infection control guidelines and support the broader implementation of CHG-based decolonization and stewardship strategies in similar healthcare environments.

Study Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-06-06
• Study First Submitted QC: 2025-06-24
• Study First Posted: 2025-06-26
• Study Start: 2025-07-14
• Last Update Submitted: 2025-07-18
• Last Update Posted: 2025-07-23
• Primary Completion: 2026-07-14
• Study Completion: 2026-08-31

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 5760

Inclusion Criteria

1. Adults aged 19 years or older

2. Admitted to one of the participating intensive care units (ICUs):

   • Chuncheon Sacred Heart Hospital: CICU or NCU
   • Wonju Severance Christian Hospital: MICU or NSICU
   • Gangneung Asan Hospital: MICU or SICU

Exclusion Criteria

1. Age 18 years or younger
2. Patients with extensive burns
3. Patients with a known hypersensitivity to chlorhexidine

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
Incidence of CPE Colonization and Infection	From ICU admission up to ICU discharge (an average of 10-14 days)	Incidence of new colonization or infection with carbapenemase-producing Enterobacteriaceae (CPE) during ICU admission, confirmed through active surveillance cultures (e.g., rectal swab) and clinical diagnostic specimens (e.g., blood, respiratory, or urine cultures).; Infections will be defined according to CDC/NHSN criteria for healthcare-associated infections.

Secondary Outcome Measures

Name	Time	Method
Residual CHG Skin Concentration vs. CPE MIC Comparison	Measured at 3-month intervals during intervention periods	Assessment of residual skin concentrations of chlorhexidine gluconate (CHG) using standardized skin swabs, and comparison with the minimum inhibitory concentrations (MICs) of CPE isolates obtained from clinical or surveillance cultures to determine adequacy of CHG exposure.
Proportion of CHG Bathing Days Adherent to Protocol Based on CHG Skin Concentration, Checklist Compliance, and EMR Audit	Approximately Day 15 of Months 0, 3, and 6 during the intervention period	This outcome assesses adherence to the daily chlorhexidine gluconate (CHG) bathing protocol among ICU patients. Adherence will be evaluated using a combination of: 1. Colorimetric CHG skin concentration testing, with adherence defined as CHG concentration ≥125 µg/mL on at least 2 of 3 body sites; 2. Chlorhexidine Bathing Checklist completed by bedside staff; and; 3. Electronic Medical Record (EMR) audit for daily documentation of CHG bathing.; Feedback on adherence results will be provided to ICU staff, and its impact on improving adherence rates will be evaluated.
Incidence of Adverse Skin Reactions Related to CHG Bathing	Daily during the intervention period, from ICU admission up to ICU discharge (an average of 10-14 days)	Monitoring and reporting of adverse skin reactions (e.g., erythema, rash, itching, blistering) associated with daily chlorhexidine bathing using 4% CHG-impregnated washcloths. Skin assessments will be conducted by trained staff through direct observation and chart review.
Monthly Trends in Antimicrobial and PPI Use	Monthly, from intervention start (Month 1) to study end (Month 12)	Monthly analysis of antimicrobial and PPI utilization, measured as days of therapy (DOT) per 1,000 patient-days, including carbapenems, ampicillin/sulbactam, ceftazidime/avibactam, cefiderocol, and PPI vs. H2 blocker use.

Trial Locations

Locations (3)

Chuncheon Sacred Heart Hospital, Hallym University College of Medicine; 🇰🇷 Chuncheon, Gangwon-do, Korea, Republic of

Gangneung Asan Hospital, University of Ulsan College of Medicine; 🇰🇷 Gangneung, Gangwon-do, Korea, Republic of

Wonju Severance Christian Hospital, Yonsei University Health System; 🇰🇷 Wŏnju, Gangwon-do, Korea, Republic of