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

NCT07039955 | Enrolling By Invitation DMC

• 1 other identifier: 2025-05-001
• Study Type: interventional
• Target: 5,760
• Locations: 1 country
• Sites: 3

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.

Conditions

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

Keywords

Carbapenemase-Producing Enterobacteriaceae; Healthcare-Associated Infections; Intensive Care Unit; infection control; Daily Chlorhexidine Bathing; Antimicrobial Stewardship; Proton Pump Inhibitor Stewardship; Chlorhexidine (CHG) Skin Concentration; Chlorhexidine (CHG) Minimum Inhibitory Concentration (MIC)

Outcome Measures

Primary Outcomes (1)

• Incidence of CPE Colonization and Infection

  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.

  From ICU admission up to ICU discharge (an average of 10-14 days)

Secondary Outcomes (4)

• Residual CHG Skin Concentration vs. CPE MIC Comparison

  Measured at 3-month intervals during intervention periods

• 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

• 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)

• Monthly Trends in Antimicrobial and PPI Use

  Monthly, from intervention start (Month 1) to study end (Month 12)

Study Arms (2)

CHG Bathing + Antimicrobial/PPI Stewardship

EXPERIMENTAL

Patients admitted to intensive care units (ICUs) assigned to the intervention group will receive daily bathing using no-rinse, 4% chlorhexidine gluconate (CHG)-impregnated washcloths. In addition, targeted antimicrobial stewardship focused on reducing unnecessary carbapenem use and PPI stewardship aimed at limiting inappropriate PPI prescriptions will be implemented.

Behavioral: Daily Chlorhexidine Bathing; Behavioral: Antimicrobial and PPI Stewardship Program

Standard Bathing + Antimicrobial/PPI Stewardship

ACTIVE COMPARATOR

Patients admitted to ICUs assigned to the control group will receive standard daily bathing without chlorhexidine. The same antimicrobial and PPI stewardship interventions applied in the intervention group will also be implemented in the control group.

Behavioral: Antimicrobial and PPI Stewardship Program; Behavioral: Standard Bathing

Interventions

Daily Chlorhexidine Bathing BEHAVIORAL

Daily bathing using no-rinse, 4% chlorhexidine gluconate (CHG)-impregnated washcloths will be implemented in ICUs assigned to the intervention group. The purpose is to reduce CPE colonization and infection by maintaining effective residual CHG skin concentrations. Bathing will be performed by trained nursing staff following standardized protocols.

CHG Bathing + Antimicrobial/PPI Stewardship

Antimicrobial and PPI Stewardship Program BEHAVIORAL

A targeted stewardship program will be implemented to reduce unnecessary carbapenem use and inappropriate proton pump inhibitor (PPI) prescriptions. The program includes audit and feedback, education of ICU physicians, and monthly monitoring of antimicrobial and PPI usage. Stewardship activities will be uniformly applied across both intervention and control ICUs.

CHG Bathing + Antimicrobial/PPI Stewardship; Standard Bathing + Antimicrobial/PPI Stewardship

Standard Bathing BEHAVIORAL

Patients in ICUs assigned to the control group will receive standard daily bathing without the use of chlorhexidine. No CHG-containing products will be applied. This represents usual care in the participating hospitals.

Standard Bathing + Antimicrobial/PPI Stewardship

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged 19 years or older
• 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

You may not qualify if:

• Age 18 years or younger
• Patients with extensive burns
• Patients with a known hypersensitivity to chlorhexidine

Sponsors & Collaborators

• Chuncheon Sacred Heart Hospital: lead
• Wonju Severance Christian Hospital: collaborator
• Gangneung Asan Hospital: collaborator
• National Institute of Health, Korea: collaborator

Study Sites (3)

Chuncheon Sacred Heart Hospital, Hallym University College of Medicine

Chuncheon, Gangwon-do, 24253, South Korea

Location

Gangneung Asan Hospital, University of Ulsan College of Medicine

Gangneung, Gangwon-do, 25440, South Korea

Location

Wonju Severance Christian Hospital, Yonsei University Health System

Wŏnju, Gangwon-do, 26426, South Korea

Location

Related Publications (5)

• Rhee Y, Hayden MK, Schoeny M, Baker AW, Baker MA, Gohil S, Rhee C, Talati NJ, Warren DK, Welbel S, Lolans K, Bahadori B, Bell PB, Bravo H, Dangana T, Fukuda C, Habrock Bach T, Nelson A, Simms AT, Tolomeo P, Wolf R, Yelin R, Lin MY; CDC Prevention Epicenters Program. Impact of measurement and feedback on chlorhexidine gluconate bathing among intensive care unit patients: A multicenter study. Infect Control Hosp Epidemiol. 2023 Sep;44(9):1375-1380. doi: 10.1017/ice.2023.177. Epub 2023 Sep 13.

  PMID: 37700540 BACKGROUND

• Willems RPJ, van Dijk K, Ket JCF, Vandenbroucke-Grauls CMJE. Evaluation of the Association Between Gastric Acid Suppression and Risk of Intestinal Colonization With Multidrug-Resistant Microorganisms: A Systematic Review and Meta-analysis. JAMA Intern Med. 2020 Apr 1;180(4):561-571. doi: 10.1001/jamainternmed.2020.0009.

  PMID: 32091544 BACKGROUND

• Rhee Y, Simms AT, Schoeny M, Baker AW, Baker MA, Gohil S, Rhee C, Talati NJ, Warren DK, Welbel S, Lolans K, Bell PB, Fukuda C, Hayden MK, Lin MY; CDC Prevention Epicenters Program. Relationship between chlorhexidine gluconate concentration and microbial colonization of patients' skin. Infect Control Hosp Epidemiol. 2024 May 28:1-6. doi: 10.1017/ice.2024.81. Online ahead of print.

  PMID: 38804007 BACKGROUND

• Patel A, Parikh P, Dunn AN, Otter JA, Thota P, Fraser TG, Donskey CJ, Deshpande A. Effectiveness of daily chlorhexidine bathing for reducing gram-negative infections: A meta-analysis. Infect Control Hosp Epidemiol. 2019 Apr;40(4):392-399. doi: 10.1017/ice.2019.20. Epub 2019 Feb 26.

  PMID: 30803462 BACKGROUND

• Climo MW, Yokoe DS, Warren DK, Perl TM, Bolon M, Herwaldt LA, Weinstein RA, Sepkowitz KA, Jernigan JA, Sanogo K, Wong ES. Effect of daily chlorhexidine bathing on hospital-acquired infection. N Engl J Med. 2013 Feb 7;368(6):533-42. doi: 10.1056/NEJMoa1113849.

  PMID: 23388005 BACKGROUND

MeSH Terms

Conditions

Cross Infection

Interventions

Anti-Infective Agents

Condition Hierarchy (Ancestors)

Infections; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Cluster-randomized crossover trial involving six intensive care units (ICUs) across three university-affiliated hospitals. Each hospital contributes two ICUs, which are randomized to either the intervention or control group for six months, followed by crossover to the opposite group.

Study Record Dates

• First Submitted: June 6, 2025
• First Posted: June 26, 2025
• Study Start: July 14, 2025
• Primary Completion (Estimated): July 14, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: July 23, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

KR (3)