Elsevier

The Lancet

Volume 393, Issue 10177, 23–29 March 2019, Pages 1205-1215
The Lancet

Articles
Chlorhexidine versus routine bathing to prevent multidrug-resistant organisms and all-cause bloodstream infections in general medical and surgical units (ABATE Infection trial): a cluster-randomised trial

https://doi.org/10.1016/S0140-6736(18)32593-5Get rights and content

Summary

Background

Universal skin and nasal decolonisation reduces multidrug-resistant pathogens and bloodstream infections in intensive care units. The effect of universal decolonisation on pathogens and infections in non-critical-care units is unknown. The aim of the ABATE Infection trial was to evaluate the use of chlorhexidine bathing in non-critical-care units, with an intervention similar to one that was found to reduce multidrug-resistant organisms and bacteraemia in intensive care units.

Methods

The ABATE Infection (active bathing to eliminate infection) trial was a cluster-randomised trial of 53 hospitals comparing routine bathing to decolonisation with universal chlorhexidine and targeted nasal mupirocin in non-critical-care units. The trial was done in hospitals affiliated with HCA Healthcare and consisted of a 12-month baseline period from March 1, 2013, to Feb 28, 2014, a 2-month phase-in period from April 1, 2014, to May 31, 2014, and a 21-month intervention period from June 1, 2014, to Feb 29, 2016. Hospitals were randomised and their participating non-critical-care units assigned to either routine care or daily chlorhexidine bathing for all patients plus mupirocin for known methicillin-resistant Staphylococcus aureus (MRSA) carriers. The primary outcome was MRSA or vancomycin-resistant enterococcus clinical cultures attributed to participating units, measured in the unadjusted, intention-to-treat population as the HR for the intervention period versus the baseline period in the decolonisation group versus the HR in the routine care group. Proportional hazards models assessed differences in outcome reductions across groups, accounting for clustering within hospitals. This trial is registered with ClinicalTrials.gov, number NCT02063867.

Findings

There were 189 081 patients in the baseline period and 339 902 patients (156 889 patients in the routine care group and 183 013 patients in the decolonisation group) in the intervention period across 194 non-critical-care units in 53 hospitals. For the primary outcome of unit-attributable MRSA-positive or VRE-positive clinical cultures (figure 2), the HR for the intervention period versus the baseline period was 0·79 (0·73–0·87) in the decolonisation group versus 0·87 (95% CI 0·79–0·95) in the routine care group. No difference was seen in the relative HRs (p=0·17). There were 25 (<1%) adverse events, all involving chlorhexidine, among 183 013 patients in units assigned to chlorhexidine, and none were reported for mupirocin.

Interpretation

Decolonisation with universal chlorhexidine bathing and targeted mupirocin for MRSA carriers did not significantly reduce multidrug-resistant organisms in non-critical-care patients.

Funding

National Institutes of Health.

Introduction

Extensive reductions in health-care-associated infections have been achieved in the USA, largely because of successful infection prevention efforts in intensive care units (ICUs).1 Investments in infection reduction have led to several multicentre trials of infection prevention strategies in ICUs.2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 Notably, several recent trials of universal decolonisation involving daily chlorhexidine bathing with and without nasal mupirocin prompted widespread adoption of this practice in ICUs, because of evidence that universal decolonisation reduces device-associated bacteraemia, all-cause bacteraemia, and multidrug-resistant organisms.7, 8, 9, 10, 11, 12, 13

Although the patient-specific risk is highest in ICUs, most health-care-associated infections occur outside the ICU, because the patient populations are so much larger. Questions remain about the use of ICU-proven strategies across entire hospitals, because they could potentially have a higher cost-to-benefit ratio and lower overall effect on infection prevention.

Research in context

Evidence before this study

Several cluster-randomised trials in intensive care units (ICUs) have led to the widespread adoption of universal ICU decolonisation involving daily chlorhexidine bathing with or without nasal ointments to prevent bloodstream infections and methicillin-resistant Staphylococcus aureus (MRSA).These trials have also led to national guidance in the USA for the use of daily chlorhexidine bathing in ICUs to reduce device-associated infections, specifically central line-associated bloodstream infections. Only modest experimental evidence has been gathered about the effect of universal decolonisation in non-ICU settings. We searched PubMed for “chlorhexidine bathing” (MeSH Terms) and “hospital,” excluding “intensive care unit”, or “ICU” and found four quasi-experimental studies. One study found a 64% reduction in hospital-associated MRSA and vancomycin-resistant enterococcus (VRE) infections compared with historical controls after 14 months of daily bathing with chlorhexidine in four general medical units at an academic centre. Another study found a 55% reduction in hospital-associated MRSA and a 36% reduction in hospital-associated VRE after chlorhexidine bathing for 7 months in a crossover study of four general medical units at an academic centre. A third study with a non-randomised, stepped-wedge design involving 19 months of hospital-wide chlorhexidine bathing reported a 29% reduction in Clostridium difficile infection with thrice weekly chlorhexidine bathing, and a 59% reduction in C difficile infection with daily chlorhexidine bathing. In the last study, one chronic care hospital unit was randomly assigned to bathe patients daily with chlorhexidine for 12 months resulting in a 71% reduction in MRSA incidence among 122 patients, although the reported benefit was not significant. All but one study used 2% no-rinse chlorhexidine cloths. Reported adherence with chlorhexidine bathing in these studies was approximately 60%.

Added value of this study

The ABATE Infection (active bathing to eliminate infection) trial is the first large-scale cluster-randomised trial to evaluate whether universal chlorhexidine bathing for all patients plus mupirocin for MRSA carriers in non-critical-care units reduces multidrug-resistant organisms and all-cause bloodstream infection. Chlorhexidine compliance was higher than in the four quasi-experimental studies reported above. We found that universal decolonisation did not reduce infection in the overall population, but in post-hoc analyses of patients with medical devices the regimen was associated with significant reductions in all-cause bloodstream infections and MRSA or VRE clinical cultures.

Implications of all the available evidence

Although previous single-centre, quasi-experimental studies in non-ICU settings found broad infection reduction benefits with daily chlorhexidine use in patients in academic hospitals, the ABATE Infection trial did not find significant benefits in non-critical-care patients. Our results contrast with those showing benefits of universal decolonisation over routine care in several trials of ICUs. Current US ICU guidance to use daily chlorhexidine bathing for prevention of central line-associated infections has led many hospitals to adopt daily chlorhexidine bathing for all patients with central lines and other devices, although evidence in non-ICU patients has been lacking. The post-hoc analysis in the ABATE Infection trial found that non-ICU patients with medical devices had a significant 37% reduction in MRSA and VRE and a significant 32% reduction in all-cause bloodstream infections. Patients with medical devices constituted only 10% of the inpatient population, but were responsible for 37% of MRSA and VRE cultures and 56% of all-cause bloodstream infections. Despite these findings, further research is needed to confirm these effects if the decolonisation strategy is applied only to patients with medical devices, since the ABATE Infection trial involved universal decolonisation in all patients.

We aimed to evaluate the use of chlorhexidine bathing in non-critical-care units, with an intervention similar to one that was found to reduce multidrug-resistant organisms and bacteraemia in ICUs.7

Section snippets

Study design and participants

The ABATE Infection (active bathing to eliminate infection) trial was a cluster-randomised trial of 53 hospitals comparing routine bathing to decolonisation with universal chlorhexidine and targeted nasal mupirocin in non-critical-care units. Central institutional review board (IRB) approval was obtained from Harvard Pilgrim Health Care (Boston, MA, USA) with a waiver of informed consent. All participating hospitals formally ceded IRB oversight to the Harvard Pilgrim Health Care IRB, except for

Results

158 hospitals in 14 US states were invited to participate, and 53 were enrolled and randomised. Collectively, participating hospitals had 194 non-critical-care units (64 medical, 26 surgical, 72 mixed medical-surgical, seven oncology, and 25 step-down units).

Five hospitals withdrew after the intervention period started: two hospitals in the routine care group because of competing interventions, and three hospitals in the decolonisation group because of a competing intervention, closure of the

Discussion

There has been widespread adoption of chlorhexidine bathing with or without nasal decolonisation in ICUs across the USA and other countries, in response to cluster-randomised trials24, 25, 26, 27 showing marked reductions in central line-associated bloodstream infections and all-cause bloodstream infections, and reductions in MRSA carriage and transmission. The success of this strategy in ICUs has raised questions about whether the benefit could be extended to other populations, such as

Data sharing

The ABATE Infection trial dataset involves data on over half a million patients. Data sharing requests will be addressed through a supervised data enclave,38 which will be maintained behind HCA's firewall on HCA servers for 3 years after the primary publication date. Requests are subject to approval based on planned use of the data, protection of privacy, and scope consistent with the outcomes of the ABATE Infection trial. Only aggregate data (eg, counts, distributions) will be returned. No

References (38)

  • I Raad et al.

    Central venous catheters coated with minocycline and rifampin for the prevention of catheter-related colonization and bloodstream infections: a randomized, double-blind trial

    Ann Intern Med

    (1997)
  • de SmetAM et al.

    Decontamination of the digestive tract and oropharynx in ICU patients

    N Engl J Med

    (2009)
  • AD Harris et al.

    Universal glove and gown use and acquisition of antibiotic-resistant bacteria in the ICU: a randomized trial

    JAMA

    (2013)
  • SS Huang et al.

    Targeted versus universal decolonization to prevent ICU infection

    N Engl J Med

    (2013)
  • MW Climo et al.

    Effect of daily chlorhexidine bathing on hospital-acquired infection

    N Engl J Med

    (2013)
  • E Septimus et al.

    Closing the translation gap: toolkit-based implementation of universal decolonization in adult intensive care units reduces central line-associated bloodstream infections in 95 community hospitals

    Clin Infect Dis

    (2016)
  • SS Huang et al.

    Cost savings of universal decolonization to prevent intensive care unit infection: implications of the REDUCE MRSA trial

    Infect Control Hosp Epidemiol

    (2014)
  • PC Mahalanobis

    On the generalised distance in statistics

    Proc Natl Inst Sci India

    (1936)
  • C Liu et al.

    Clinical practice guidelines by the infectious diseases society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children

    Clin Infect Dis

    (2011)
  • Cited by (80)

    • Best products for skin antisepsis

      2023, American Journal of Infection Control
    • Reduction in patient refusal of CHG bathing

      2023, American Journal of Infection Control
    View all citing articles on Scopus
    View full text