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 ß-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.

Outpatient Antibiotic Prescriptions in France: Patients and Providers Characteristics and Impact of the COVID-19 Pandemic.

In France, despite several successive plans to control antimicrobial resistance, antibiotic use remains high in the outpatient setting. This study aims to better understand outpatient antibiotic use and prescription in order to identify tailored targets for future public health actions. Using data from the French National Health Data System, we described and compared the individual characteristics of patients with and without an antibiotic prescription. The prescribed antibiotics (ATC-J01) were detailed and compared between 2019 and 2020. Antibiotic prescribing indicators that take prescriber activity into account were estimated and compared. Patients who were female, advanced age, and the presence of comorbidities were associated with antibiotic prescriptions. The overall prescription rate was estimated at 134 per 1000 consultations and 326 per 1000 patients seen in 2019. General practitioners (GPs), dentists and paediatricians were associated with 78.0%, 12.2% and 2.2% of antibiotic prescriptions, respectively, with high prescription rates (391, 447, and 313 p. 1000 patients seen, respectively). In comparison with 2019, this rate decreased in 2020 for paediatricians (-30.4%) and GPs (-17.9%) whereas it increased among dentists (+17.9%). The reduction was twice as high among the male prescribers than among their female counterparts (-26.6 and -12.0, respectively). The reduction in prescriptions observed in 2020 (-18.2%) was more marked in children (-35.8%) but less so among individuals ≥65 years (-13.1%) and those with comorbidities (-12.5%). The decrease in penicillin prescriptions represents 67.3% of the overall reduction observed in 2020. The heterogeneous decrease in prescriptions by age and antibiotic class could be explained by the impact of COVID-19 control measures on the spread of respiratory viruses; thus, a substantial proportion of the prescriptions avoided in 2020 is likely inappropriate, particularly among children. In order to keep the rate of prescriptions comparable to that observed in 2020, male prescribers, paediatricians and GPs should be encouraged to maintain that level, while a campaign to raise awareness of the appropriate use of antibiotics should be aimed at dentists in particular.