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Decontamination strategies and bloodstream infections with antibiotic-resistant microorganisms in ventilated patients : a randomized clinical trial

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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, ANDPARTICIPANTS: RandomizedtrialconductedfromDecember1,2013, toMay 31, 2017, in 13 European ICUs where at least 5% of bloodstream infections are caused by extendedspectrum beta-lactamase-producingEnterobacteriaceae. Patientswithanticipatedmechanicalventilation of more than 24 hourswere eligible. The final date of follow-upwas September 20, 2017. INTERVENTIONS: Standard carewas daily CHX 2% bodywashings and a hand hygiene improvement program. Following a baseline period from 6 to 14 months, each ICUwas 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.
Keywords
INTENSIVE-CARE UNITS, SELECTIVE DECONTAMINATION, DIGESTIVE-TRACT, INTESTINAL-TRACT, OROPHARYNX, MORTALITY, BACTERIA, ICUS

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MLA
Wittekamp, Bastiaan H, Nienke L Plantinga, Ben S Cooper, et al. “Decontamination Strategies and Bloodstream Infections with Antibiotic-resistant Microorganisms in Ventilated Patients : a Randomized Clinical Trial.” JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION 320.20 (2018): 2087–2098. Print.
APA
Wittekamp, B. H., Plantinga, N. L., Cooper, B. S., Lopez-Contreras, J., Coll, P., Mancebo, J., Wise, M. P., et al. (2018). Decontamination strategies and bloodstream infections with antibiotic-resistant microorganisms in ventilated patients : a randomized clinical trial. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 320(20), 2087–2098.
Chicago author-date
Wittekamp, Bastiaan H, Nienke L Plantinga, Ben S Cooper, Joaquin Lopez-Contreras, Pere Coll, Jordi Mancebo, Matt P Wise, et al. 2018. “Decontamination Strategies and Bloodstream Infections with Antibiotic-resistant Microorganisms in Ventilated Patients : a Randomized Clinical Trial.” Jama-journal of the American Medical Association 320 (20): 2087–2098.
Chicago author-date (all authors)
Wittekamp, Bastiaan H, Nienke L Plantinga, Ben S Cooper, Joaquin Lopez-Contreras, Pere Coll, Jordi Mancebo, Matt P Wise, Matt PG Morgan, Pieter Depuydt, Jerina Boelens, Thierry Dugernier, Valérie Verbelen, Philippe G Jorens, Walter Verbrugghe, Surbhi Malhotra-Kumar, Pierre Damas, Cécile Meex, Kris Leleu, Anne-Marie van den Abeele, Ana Filipa Gomes Pimenta de Matos, Sara Fernández Méndez, Andrea Vergara Gomez, Viktorija Tomic, Franc Sifrer, Esther Villarreal Tello, Jesus Ruiz Ramos, Irene Aragao, Claudia Santos, Roberta HM Sperning, Patrizia Coppadoro, Giuseppe Nardi, Christian Brun-Buisson, and Marc JM Bonten. 2018. “Decontamination Strategies and Bloodstream Infections with Antibiotic-resistant Microorganisms in Ventilated Patients : a Randomized Clinical Trial.” Jama-journal of the American Medical Association 320 (20): 2087–2098.
Vancouver
1.
Wittekamp BH, Plantinga NL, Cooper BS, Lopez-Contreras J, Coll P, Mancebo J, et al. Decontamination strategies and bloodstream infections with antibiotic-resistant microorganisms in ventilated patients : a randomized clinical trial. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION. 2018;320(20):2087–98.
IEEE
[1]
B. H. Wittekamp et al., “Decontamination strategies and bloodstream infections with antibiotic-resistant microorganisms in ventilated patients : a randomized clinical trial,” JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, vol. 320, no. 20, pp. 2087–2098, 2018.
@article{8585849,
  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, ANDPARTICIPANTS: RandomizedtrialconductedfromDecember1,2013, toMay 31, 2017, in 13 European ICUs where at least 5% of bloodstream infections are caused by extendedspectrum beta-lactamase-producingEnterobacteriaceae. Patientswithanticipatedmechanicalventilation of more than 24 hourswere eligible. The final date of follow-upwas September 20, 2017. 
INTERVENTIONS: Standard carewas daily CHX 2% bodywashings and a hand hygiene improvement program. Following a baseline period from 6 to 14 months, each ICUwas 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.},
  author       = {Wittekamp, Bastiaan H and Plantinga, Nienke L and Cooper, Ben S and Lopez-Contreras, Joaquin and Coll, Pere and Mancebo, Jordi and Wise, Matt P and Morgan, Matt PG and Depuydt, Pieter and Boelens, Jerina and Dugernier, Thierry and Verbelen, Valérie and Jorens, Philippe G and Verbrugghe, Walter and Malhotra-Kumar, Surbhi and Damas, Pierre and Meex, Cécile and Leleu, Kris and van den Abeele, Anne-Marie and Gomes Pimenta de Matos, Ana Filipa and Fernández Méndez, Sara and Vergara Gomez, Andrea and Tomic, Viktorija and Sifrer, Franc and Villarreal Tello, Esther and Ruiz Ramos, Jesus and Aragao, Irene and Santos, Claudia and Sperning, Roberta HM and Coppadoro, Patrizia and Nardi, Giuseppe and Brun-Buisson, Christian and Bonten, Marc JM},
  issn         = {0098-7484},
  journal      = {JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION},
  keywords     = {INTENSIVE-CARE UNITS,SELECTIVE DECONTAMINATION,DIGESTIVE-TRACT,INTESTINAL-TRACT,OROPHARYNX,MORTALITY,BACTERIA,ICUS},
  language     = {eng},
  number       = {20},
  pages        = {2087--2098},
  title        = {Decontamination strategies and bloodstream infections with antibiotic-resistant microorganisms in ventilated patients : a randomized clinical trial},
  url          = {http://dx.doi.org/10.1001/jama.2018.13765},
  volume       = {320},
  year         = {2018},
}

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