Interventions to reduce colonisation and transmission of antimicrobial-resistant bacteria in intensive care units: an interrupted time series study and cluster randomised trial

Abstract

Background: Intensive care units (ICUs) are high-risk areas for transmission of antimicrobial-resistant bacteria, but no controlled study has tested the effect of rapid screening and isolation of carriers on transmission in settings with best-standard precautions. We assessed interventions to reduce colonisation and transmission of antimicrobial-resistant bacteria in European ICUs.

Methods: We did this study in three phases at 13 ICUs. After a 6 month baseline period (phase 1), we did an interrupted time series study of universal chlorhexidine body-washing combined with hand hygiene improvement for 6 months (phase 2), followed by a 12-15 month cluster randomised trial (phase 3). ICUs were randomly assigned by computer generated randomisation schedule to either conventional screening (chromogenic screening for meticillin-resistant Staphylococcus aureus [MRSA] and vancomycin-resistant enterococci [VRE]) or rapid screening (PCR testing for MRSA and VRE and chromogenic screening for highly resistant Enterobacteriaceae [HRE]); with contact precautions for identified carriers. The primary outcome was acquisition of resistant bacteria per 100 patient-days at risk, for which we calculated step changes and changes in trends after the introduction of each intervention. We assessed acquisition by microbiological surveillance and analysed it with a multilevel Poisson segmented regression model. We compared screening groups with a likelihood ratio test that combined step changes and changes to trend. This study is registered with ClinicalTrials.gov, number NCT00976638.

Findings: Seven ICUs were assigned to rapid screening and six to conventional screening. Mean hand hygiene compliance improved from 52% in phase 1 to 69% in phase 2, and 77% in phase 3. Median proportions of patients receiving chlorhexidine body-washing increased from 0% to 100% at the start of phase 2. For trends in acquisition of antimicrobial-resistant bacteria, weekly incidence rate ratio (IRR) was 0·976 (0·954-0·999) for phase 2 and 1·015 (0·998-1·032) for phase 3. For step changes, weekly IRR was 0·955 (0·676-1·348) for phase 2 and 0·634 (0·349-1·153) for phase 3. The decrease in trend in phase 2 was largely caused by changes in acquisition of MRSA (weekly IRR 0·925, 95% CI 0·890-0·962). Acquisition was lower in the conventional screening group than in the rapid screening group, but did not differ significantly (p=0·06).

Interpretation: Improved hand hygiene plus unit-wide chlorhexidine body-washing reduced acquisition of antimicrobial-resistant bacteria, particularly MRSA. In the context of a sustained high level of compliance to hand hygiene and chlorhexidine bathings, screening and isolation of carriers do not reduce acquisition rates of multidrug-resistant bacteria, whether or not screening is done with rapid testing or conventional testing.

Funding: European Commission.

Figure 1

Study profile Patients at risk for acquiring colonisation with AMRB excludes all patients colonised at admission with any of MRSA, VRE, HRE, or in whom a first (admission) swab was taken after the first 2 days of ICU stay and was positive. AMRB=antimicrobial-resistant bacteria. ICU=intensive care unit. MRSA=meticillin-resistant Staphylococcus aureus. VRE=vancomycin-resistant enterococci. HRE=highly resistant Enterobacteriaceae. *Admitted for at least 3 days, for whom admission and discharge data were available and of whom at least one nasal, rectal, or wound swab was obtained during ICU admission.

Figure 2

Mean hand hygiene compliance per month Hand hygiene improvement intervention introduced at month 0. Error bars are 95% CIs.

Figure 3

Acquisition of antimicrobial-resistant bacteria and meticillin-resistant Staphylococcus aureus per 100 patient-days at risk For all antimicrobial bacteria in both screening groups (A), for MRSA in both screening groups (B), for all antimicrobial bacteria in the conventional screening group (C), for MRSA in the conventional screening group (D), for all antimicrobial bacteria in the rapid screening group (E), and for MRSA in the rapid screening group (F). Shaded area is the start of phase 3. Green dots are data; green lines are 7 week moving average. Red lines are expected values from the multilevel Poisson segmented regression model. Cluster effects were accounted for, and potential confounding factors (sex, age, month, invasive devices, nurse-to-patient staffing ratio, location before ICU admission, reason for admission, APACHE and SAPS score, hospital, and number of days-at-risk for acquisition) were fitted as covariates. APACHE=Acute Physiology and Chronic Health Evaluation. SAPS=Simplified Acute Physiology Score.