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

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 NCT02208154

Audio-visual (A/V) stimuli used in the present study.

<p>Monosyllabic sound /be/ spoken by a Japanese male speaker was presented under six different visual conditions: 1) control: visual noise created by applying a strong Gaussian filter of a PC software (Adobe^® Photoshop) to a still image of the speaker’s face, and moving image of the same speaker’s face uttering /ge/ (incongruent visual stimuli known to evoke McGurk effect); 2) with synchronous conditions (no A/V lag) (A/V 0); 3) with +500 ms audio lag (A/V +500); 4) with +100 ms audio lag (A/V +100); 5) with -100 ms audio lag or +100 ms audio lead (A/V -100); and 6) with -500 ms audio lag or +500 ms audio lead (A/V -500). Each visual stimulus was prepared as a video clip with duration of 3 s. Audio stimulus started 1400 ms after the beginning of the visual stimulus and lasted for approximately 180 ms under the A/V 0 as well as control conditions (A/V noise). The presentation timing of audio stimuli were preceded or delayed 100 and 500 ms under A/V +/-100 and +/-500 ms conditions, respectively. The still images of visual stimuli at the timing points of -500 ms, -300 ms, -100 ms, 0 ms (at the onset of utterance), +100 ms, +300 ms, and +500 ms after the onset of utterance represent the moving images of uttering /ge/ (these face images in Fig 1 were treated with a digital filter except for the area around the mouth, so that the individual can not be identified). The movement of the speaker’s mouth started just before the time point -300 ms (300 ms before the onset of utterance) and ended just after the time point +300 ms (300 ms after the onset of utterance).</p