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

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. To determine associations between CHX 2%, SOD, and SDD and t...

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Vydáno v:JAMA : the journal of the American Medical Association Ročník 320; číslo 20; s. 2087
Hlavní autoři: Wittekamp, Bastiaan H, Plantinga, Nienke L, Cooper, Ben S, Lopez-Contreras, Joaquin, Coll, Pere, Mancebo, Jordi, Wise, Matt P, Morgan, Matt P G, Depuydt, Pieter, Boelens, Jerina, Dugernier, Thierry, Verbelen, Valérie, Jorens, Philippe G, Verbrugghe, Walter, Malhotra-Kumar, Surbhi, Damas, Pierre, Meex, Cécile, Leleu, Kris, van den Abeele, Anne-Marie, Gomes Pimenta de Matos, Ana Filipa, Fernández Méndez, Sara, Vergara Gomez, Andrea, Tomic, Viktorija, Sifrer, Franc, Villarreal Tello, Esther, Ruiz Ramos, Jesus, Aragao, Irene, Santos, Claudia, Sperning, Roberta H M, Coppadoro, Patrizia, Nardi, Giuseppe, Brun-Buisson, Christian, Bonten, Marc J M
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 27.11.2018
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ISSN:1538-3598, 1538-3598
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Abstract 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. 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. 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. 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. 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. 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. 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. ClinicalTrials.gov Identifier: NCT02208154.
AbstractList 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.ImportanceThe 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.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.ObjectiveTo 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.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.Design, Setting, and ParticipantsRandomized 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.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.InterventionsStandard 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.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.Main Outcomes and MeasuresThe 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.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.ResultsA 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.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.Conclusions and RelevanceAmong 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.ClinicalTrials.gov Identifier: NCT02208154.Trial RegistrationClinicalTrials.gov Identifier: NCT02208154.
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. 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. 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. 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. 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. 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. 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. ClinicalTrials.gov Identifier: NCT02208154.
Author Depuydt, Pieter
Leleu, Kris
van den Abeele, Anne-Marie
Vergara Gomez, Andrea
Sifrer, Franc
Coll, Pere
Damas, Pierre
Wise, Matt P
Malhotra-Kumar, Surbhi
Meex, Cécile
Nardi, Giuseppe
Mancebo, Jordi
Tomic, Viktorija
Fernández Méndez, Sara
Verbrugghe, Walter
Boelens, Jerina
Jorens, Philippe G
Sperning, Roberta H M
Gomes Pimenta de Matos, Ana Filipa
Dugernier, Thierry
Verbelen, Valérie
Lopez-Contreras, Joaquin
Villarreal Tello, Esther
Coppadoro, Patrizia
Santos, Claudia
Brun-Buisson, Christian
Cooper, Ben S
Aragao, Irene
Ruiz Ramos, Jesus
Morgan, Matt P G
Bonten, Marc J M
Wittekamp, Bastiaan H
Plantinga, Nienke L
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  fullname: Cooper, Ben S
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  organization: Adult Critical Care, University Hospital of Wales, Cardiff, Wales
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  organization: Adult Critical Care, University Hospital of Wales, Cardiff, Wales
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  surname: Depuydt
  fullname: Depuydt, Pieter
  organization: Intensive Care, Ghent University Hospital, Ghent, Belgium
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  givenname: Jerina
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  fullname: Boelens, Jerina
  organization: Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium
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  givenname: Thierry
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  fullname: Dugernier, Thierry
  organization: Department of Intensive Care Medicine, Clinique Saint Pierre, Ottignies-Louvain-la-Neuve, Belgium
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  givenname: Valérie
  surname: Verbelen
  fullname: Verbelen, Valérie
  organization: Microbiology Department, Clinique Saint Pierre, Ottignies-Louvain-la-Neuve, Belgium
– sequence: 13
  givenname: Philippe G
  surname: Jorens
  fullname: Jorens, Philippe G
  organization: IntensiveCare Medicine, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium
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  givenname: Walter
  surname: Verbrugghe
  fullname: Verbrugghe, Walter
  organization: IntensiveCare Medicine, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium
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  surname: Malhotra-Kumar
  fullname: Malhotra-Kumar, Surbhi
  organization: Laboratory of Medical Microbiology, Vaccine, & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
– sequence: 16
  givenname: Pierre
  surname: Damas
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  organization: Department of Intensive Care Medicine, CHU Liège, Liege, Belgium
– sequence: 17
  givenname: Cécile
  surname: Meex
  fullname: Meex, Cécile
  organization: Clinical Microbiology, CHU Liège, Liege, Belgium
– sequence: 18
  givenname: Kris
  surname: Leleu
  fullname: Leleu, Kris
  organization: Anesthesiology and Critical Care, AZ Sint Jan Bruges, Bruges, Belgium
– sequence: 19
  givenname: Anne-Marie
  surname: van den Abeele
  fullname: van den Abeele, Anne-Marie
  organization: Microbiology Laboratory, Saint-Lucas Hospital Ghent, Ghent, Belgium
– sequence: 20
  givenname: Ana Filipa
  surname: Gomes Pimenta de Matos
  fullname: Gomes Pimenta de Matos, Ana Filipa
  organization: Serviço de Medicina Intensiva, Centro Hospitalar de Trás-os-Montes os Montes e Alto Douro, Vila Real, Portugal
– sequence: 21
  givenname: Sara
  surname: Fernández Méndez
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  organization: Microbiology Department, Hospital Clinic of Barcelona, Barcelona, Spain
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  fullname: Tomic, Viktorija
  organization: Laboratory for Respiratory Microbiology, University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia
– sequence: 24
  givenname: Franc
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  organization: Intensive Care Unit, University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia
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  givenname: Esther
  surname: Villarreal Tello
  fullname: Villarreal Tello, Esther
  organization: Intensive Care Unit, Hospital Universitario La Fe, Valencia, Spain
– sequence: 26
  givenname: Jesus
  surname: Ruiz Ramos
  fullname: Ruiz Ramos, Jesus
  organization: Intensive Care Unit, Hospital Universitario La Fe, Valencia, Spain
– sequence: 27
  givenname: Irene
  surname: Aragao
  fullname: Aragao, Irene
  organization: Intensive Care (UCIP), Hospital Santo Antonio-Centro Hospitalar do Porto (CHP), Porto, Portugal
– sequence: 28
  givenname: Claudia
  surname: Santos
  fullname: Santos, Claudia
  organization: Microbiology Laboratory, Hospital Santo Antonio-Centro Hospitalar do Porto (CHP), Porto, Portugal
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  givenname: Roberta H M
  surname: Sperning
  fullname: Sperning, Roberta H M
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  fullname: Coppadoro, Patrizia
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  givenname: Giuseppe
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  organization: Department of Anesthesia and Intensive Care, Ospedale Infermi RIMINI-AUSL della Romagna, Rimini, Italy
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  givenname: Christian
  surname: Brun-Buisson
  fullname: Brun-Buisson, Christian
  organization: Medical Intensive Care and Infection Control Unit, CHU Henri Mondor & University Paris Est Créteil, Paris, France
– sequence: 33
  givenname: Marc J M
  surname: Bonten
  fullname: Bonten, Marc J M
  organization: Medical Microbiology and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands
BackLink https://www.ncbi.nlm.nih.gov/pubmed/30347072$$D View this record in MEDLINE/PubMed
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References 30964520 - JAMA. 2019 Apr 9;321(14):1409-1410. doi: 10.1001/jama.2019.0444.
30964522 - JAMA. 2019 Apr 9;321(14):1408-1409. doi: 10.1001/jama.2019.0452.
30964521 - JAMA. 2019 Apr 9;321(14):1409. doi: 10.1001/jama.2019.0448.
30347049 - JAMA. 2018 Nov 27;320(20):2081-2083. doi: 10.1001/jama.2018.13764.
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Snippet The effects of chlorhexidine (CHX) mouthwash, selective oropharyngeal decontamination (SOD), and selective digestive tract decontamination (SDD) on patient...
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SubjectTerms Adult
Aged
Aged, 80 and over
Anti-Infective Agents - therapeutic use
Bacteremia - prevention & control
Chlorhexidine - therapeutic use
Cross Infection - prevention & control
Disinfection - methods
Drug Resistance, Bacterial
Female
Gastrointestinal Tract - microbiology
Gram-Negative Bacterial Infections - prevention & control
Hospital Mortality
Humans
Intensive Care Units
Male
Middle Aged
Mouthwashes - therapeutic use
Oropharynx - microbiology
Respiration, Artificial
Young Adult
Title Decontamination Strategies and Bloodstream Infections With Antibiotic-Resistant Microorganisms in Ventilated Patients: A Randomized Clinical Trial
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