Decontamination Strategies and Bloodstream Infections With Antibiotic-Resistant Microorganisms in Ventilated Patients: A Randomized Clinical Trial

Abstract

Importance: The effects of chlorhexidine (CHX) mouthwash, selective oropharyngeal decontamination (SOD), and selective digestive tract decontamination (SDD) on patient outcomes in ICUs with moderate to high levels of antibiotic resistance are unknown.

Objective: To determine associations between CHX 2%, SOD, and SDD and the occurrence of ICU-acquired bloodstream infections with multidrug-resistant gram-negative bacteria (MDRGNB) and 28-day mortality in ICUs with moderate to high levels of antibiotic resistance.

Design, setting, and participants: Randomized trial conducted from December 1, 2013, to May 31, 2017, in 13 European ICUs where at least 5% of bloodstream infections are caused by extended-spectrum β-lactamase-producing Enterobacteriaceae. Patients with anticipated mechanical ventilation of more than 24 hours were eligible. The final date of follow-up was September 20, 2017.

Interventions: Standard care was daily CHX 2% body washings and a hand hygiene improvement program. Following a baseline period from 6 to 14 months, each ICU was assigned in random order to 3 separate 6-month intervention periods with either CHX 2% mouthwash, SOD (mouthpaste with colistin, tobramycin, and nystatin), or SDD (the same mouthpaste and gastrointestinal suspension with the same antibiotics), all applied 4 times daily.

Main outcomes and measures: The occurrence of ICU-acquired bloodstream infection with MDRGNB (primary outcome) and 28-day mortality (secondary outcome) during each intervention period compared with the baseline period.

Results: A total of 8665 patients (median age, 64.1 years; 5561 men [64.2%]) were included in the study (2251, 2108, 2224, and 2082 in the baseline, CHX, SOD, and SDD periods, respectively). ICU-acquired bloodstream infection with MDRGNB occurred among 144 patients (154 episodes) in 2.1%, 1.8%, 1.5%, and 1.2% of included patients during the baseline, CHX, SOD, and SDD periods, respectively. Absolute risk reductions were 0.3% (95% CI, -0.6% to 1.1%), 0.6% (95% CI, -0.2% to 1.4%), and 0.8% (95% CI, 0.1% to 1.6%) for CHX, SOD, and SDD, respectively, compared with baseline. Adjusted hazard ratios were 1.13 (95% CI, 0.68-1.88), 0.89 (95% CI, 0.55-1.45), and 0.70 (95% CI, 0.43-1.14) during the CHX, SOD, and SDD periods, respectively, vs baseline. Crude mortality risks on day 28 were 31.9%, 32.9%, 32.4%, and 34.1% during the baseline, CHX, SOD, and SDD periods, respectively. Adjusted odds ratios for 28-day mortality were 1.07 (95% CI, 0.86-1.32), 1.05 (95% CI, 0.85-1.29), and 1.03 (95% CI, 0.80-1.32) for CHX, SOD, and SDD, respectively, vs baseline.

Conclusions and relevance: Among patients receiving mechanical ventilation in ICUs with moderate to high antibiotic resistance prevalence, use of CHX mouthwash, SOD, or SDD was not associated with reductions in ICU-acquired bloodstream infections caused by MDRGNB compared with standard care.

Trial registration: ClinicalTrials.gov Identifier: NCT02208154.

Conflict of interest statement

Conflict of Interest Disclosures: Drs Wittekamp, Plantinga, Bonten, and Brun-Buisson report grants from the European Commission (FP7-HEALTH; 282512), during the conduct of the study. Prof Mancebo reports personal fees from Faron and Medtronic, grants from Medtronic, and other funding from IMT Medical (hotel and travel expenses to attend ISICEM meeting in 2017), Fisher & Paykel (high-flow nasal oxygen for the RINO multicenter trial), General Electric (ventilators for research in lung volumes in ARDS), and A-Lung (catheters, gas exchange cartridges, and centrifuge pumps for the SUPERNOVA multicenter trial), outside the submitted work. Dr Wise reports accommodation and travel for lecture at BARD educational meetings. No other disclosures were reported.

Figures

Figure.. Flowchart and Cohorts for Analyses

Abbreviations: ICU, intensive care unit; MV, mechanical ventilation. aSome patients had multiple reasons for exclusion. bThe cohort for hospital mortality included 8509 unique hospital admissions, 37 with missing hospital mortality status. cThe cohort for 28-day mortality included 8496 unique ICU admissions with no prior ICU admission within 30 days, 56 with missing 28-day mortality status.