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Original Investigation
Caring for the Critically Ill Patient
November 27, 2018

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

Author Affiliations
  • 1Intensive Care Center and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands
  • 2Medical Microbiology and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands
  • 3Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, England
  • 4Infectious Diseases–Internal Medicine, Hospital de Sant Pau-Universitat Autònoma de Barcelona, Barcelona, Spain
  • 5Department of Microbiology, Hospital de Sant Pau-Universitat Autònoma de Barcelona, Barcelona, Spain
  • 6Department of Intensive Care, Hospital de Sant Pau-Universitat Autònoma de Barcelona, Barcelona, Spain
  • 7Adult Critical Care, University Hospital of Wales, Cardiff, Wales
  • 8Intensive Care, Ghent University Hospital, Ghent, Belgium
  • 9Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium
  • 10Department of Intensive Care Medicine, Clinique Saint Pierre, Ottignies-Louvain-la-Neuve, Belgium
  • 11Microbiology Department, Clinique Saint Pierre, Ottignies-Louvain-la-Neuve, Belgium
  • 12IntensiveCare Medicine, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium
  • 13Laboratory of Medical Microbiology, Vaccine, & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
  • 14Department of Intensive Care Medicine, CHU Liège, Liege, Belgium
  • 15Clinical Microbiology, CHU Liège, Liege, Belgium
  • 16Anesthesiology and Critical Care, AZ Sint Jan Bruges, Bruges, Belgium
  • 17Microbiology Laboratory, Saint-Lucas Hospital Ghent, Ghent, Belgium
  • 18Serviço de Medicina Intensiva, Centro Hospitalar de Trás-os-Montes os Montes e Alto Douro, Vila Real, Portugal
  • 19Medical Intensive Care Unit, Hospital Clinic of Barcelona, Barcelona, Spain
  • 20Microbiology Department, Hospital Clinic of Barcelona, Barcelona, Spain
  • 21Laboratory for Respiratory Microbiology, University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia
  • 22Intensive Care Unit, University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia
  • 23Intensive Care Unit, Hospital Universitario La Fe, Valencia, Spain
  • 24Intensive Care (UCIP), Hospital Santo Antonio–Centro Hospitalar do Porto (CHP), Porto, Portugal
  • 25Microbiology Laboratory, Hospital Santo Antonio–Centro Hospitalar do Porto (CHP), Porto, Portugal
  • 26Department of Microbiology, Azienda Ospedaliera San Camillo Forlanini, Rome, Italy
  • 27Intensive Care Unit, Azienda Ospedaliera San Camillo Forlanini, Rome, Italy
  • 28Department of Anesthesia and Intensive Care, Ospedale Infermi RIMINI–AUSL della Romagna, Rimini, Italy
  • 29Medical Intensive Care and Infection Control Unit, CHU Henri Mondor & University Paris Est Créteil, Paris, France
JAMA. 2018;320(20):2087-2098. doi:10.1001/jama.2018.13765
Key Points

Question  Is use of chlorhexidine 2% mouthwash, selective oropharyngeal decontamination (SOD), or selective digestive tract decontamination (SDD) associated with reduced risk of bloodstream infections due to multidrug-resistant gram-negative bacteria among ventilated patients in intensive care units (ICUs) with moderate to high prevalence of antibiotic resistance?

Findings  In this randomized trial of 8665 patients, the use of chlorhexidine 1% mouthwash, SOD, or SDD was not associated with significant differences in ICU-acquired bloodstream infections with multidrug-resistant gram-negative bacteria (adjusted hazard ratios, 1.13, 0.89, and 0.70, respectively), compared with a baseline period of chlorhexidine body washing and a hand hygiene improvement program.

Meaning  Among ventilated patients in ICUs with moderate to high prevalence of antibiotic resistance, use of chlorhexidine 1% mouthwash, SOD, or SDD was not associated with a significant difference in bloodstream infections with multidrug-resistant gram-negative bacteria compared with standard care.

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

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