ImportanceAntimicrobial resistance continues to spread rapidly at a global scale. Little evidence exists on the association of antimicrobial stewardship programs (ASPs) with the consumption of antibiotics across health care and income settings.ObjectiveTo synthesize current evidence regarding the association between antimicrobial stewardship programs and the consumption of antibiotics globally.Data SourcesPubMed, Web of Science, and Scopus databases were searched from August 1, 2010, to Aug 1, 2020. Additional studies from the bibliography sections of previous systematic reviews were included.Study SelectionOriginal studies of the association of ASPs with antimicrobial consumption across health care and income settings. Animal and environmental studies were excluded.Data Extraction and SynthesisFollowing the Preferred Reporting Items in Systematic Reviews and Meta-Analyses guideline, the pooled association of targeted ASPs with antimicrobial consumption was measured using multilevel random-effects models. The Effective Public Health Practice Project quality assessment tool was used to assess study quality.Main Outcomes and MeasuresThe main outcome measures were proportion of patients receiving an antibiotic prescription and defined daily doses per 100 patient-days.ResultsOverall, 52 studies (with 1 794 889 participants) measured the association between ASPs and antimicrobial consumption and were included, with 40 studies conducted in high-income countries and 12 in low- and middle-income countries (LMICs). ASPs were associated with a 10% (95% CI, 4%-15%) reduction in antibiotic prescriptions and a 28% reduction in antibiotic consumption (rate ratio, 0.72; 95% CI, 0.56-0.92). ASPs were also associated with a 21% (95% CI, 5%-36%) reduction in antibiotic consumption in pediatric hospitals and a 28% reduction in World Health Organization watch groups antibiotics (rate ratio, 0.72; 95% CI, 0.56-0.92).Conclusions and RelevanceIn this systematic review and meta-analysis, ASPs appeared to be effective in reducing antibiotic consumption in both hospital and nonhospital settings. Impact assessment of ASPs in resource-limited settings remains scarce; further research is needed on how to best achieve reductions in antibiotic use in LMICs.

Background To prevent child deaths from severe malaria, early parenteral treatment is essential. Yet, in remote rural areas, accessing facilities offering parenteral antimalarials may be difficult. A randomised controlled trial found pre-referral treatment with rectal artesunate (RAS) to reduce deaths and disability in children who arrived at a referral facility with delay. This study examined the effectiveness of pre-referral RAS treatment implemented through routine procedures of established community-based health care systems. Methods An observational study accompanied the roll-out of RAS in the Democratic Republic of the Congo (DRC), Nigeria and Uganda. Children <5 years of age presenting to a community-based health provider with a positive malaria test and signs of severe malaria were enrolled and followed up during admission and after 28 days to assess their health status and treatment history. The primary outcome was death; covariates of interest included RAS use, referral completion, and post-referral treatment. Results Post-roll-out, RAS was administered to 88% of patients in DRC, 52% in Nigeria, and 70% in Uganda. The overall case fatality rate (CFR) was 6.7% (135/2011) in DRC, 11.7% (69/589) in Nigeria, and 0.5% (19/3686) in Uganda; 13.8% (865/6286) of patients were sick on day 28. The CFR was higher after RAS roll-out in Nigeria (16.1 vs. 4.2%) and stable in DRC (6.7 vs. 6.6%) and Uganda (0.7 vs. 0.3%). In DRC and Nigeria, children receiving RAS were more likely to die than those not receiving RAS (aOR=3.06, 95% CI 1.35–6.92 and aOR=2.16, 95% CI 1.11–4.21, respectively). Only in Uganda, RAS users were less likely to be dead or sick at follow-up (aOR=0.60, 95% CI 0.45–0.79). Post-referral parenteral antimalarials plus oral artemisinin-based combination therapy (ACT), a proxy for appropriate post-referral treatment, was protective. However, in referral health facilities, ACT was not consistently administered after parenteral treatment (DRC 68.4%, Nigeria 0%, Uganda 70.9%). Conclusions Implemented at scale to the recommended target group, pre-referral RAS had no beneficial effect on child survival in three highly malaria-endemic settings. RAS is unlikely to reduce malaria deaths unless health system issues such as referral and quality of care at all levels are addressed. Trial registration The study is registered on ClinicalTrials.gov: NCT03568344.

ObjectiveThis study aimed to examine the prevalence and determinants of benzodiazepine prescription among older adults in Switzerland, and analyse association with hospitalisation and costs.DesignRetrospective analysis of claims data.SettingThe study was conducted in nine cantons in Switzerland.ParticipantsOlder adults aged 65 years and older enrolled with a large Swiss health insurance company participated in the study.Primary and secondary outcome measuresThe primary outcome was prevalence of benzodiazepine prescription. The secondary outcomes were (1) determinants of any benzodiazepine prescription; (2) the association between any prescription and the probability of hospitalisation for trauma and (3) the association between any prescription and total healthcare expenditures.ResultsOverall, 69 005 individuals were included in the study. Approximately 20% of participants had at least one benzodiazepine prescription in 2017. Prescription prevalence increased with age (65–69: 15.9%; 70–74: 18.4%; 75–80: 22.5%; >80: 25.8%) and was higher in women (25.1%) compared with men (14.6%). Enrollees with the highest deductible of Swiss Francs (CHF) 2500 were 70% less likely to receive a prescription than enrollees with the lowest deductible of CHF 300 (adjusted OR=0.29, 95% CI 0.24 to 0.35).Individuals with at least one prescription had a higher probability of hospitalisation for trauma (OR=1.31, 95% CI 1. 20 to 1.1.44), and 70% higher health care expenditures (β=0.72, 95% CI 0. 67 to 0.77). Enrollees in canton Valais were three times more likely to receive a prescription compared to enrollees from canton Aargau (OR=2.84, 95% 2.51 to 3.21).ConclusionsThe proportion of older adults with at least one benzodiazepine prescription is high, as found in the data of one large Swiss health insurance company. These enrollees are more likely to be hospitalised for trauma and have higher healthcare expenditures. Important differences in prescription prevalence across cantons were observed, suggesting potential overuse. Further research is needed to understand the drivers of variation, prescription patterns across providers, and trends over time.