This randomized clinical trial investigates noninferiority of fosfomycin vs ceftriaxone or meropenem in achieving clinical and microbiological cure among patients with urinary tract infections due to multidrug-resistant
Escherichia coli
.
Background
Antimicrobial stewardship programs (ASPs) are recommended in nursing homes (NHs), although data are limited. This study aimed to determine the clinical and ecological impact of an ASP for NHs.
Methods
We performed a cluster randomized controlled trial and a before-after study with interrupted time-series analyses in 14 NHs, for 30 consecutive months from July 2018 to December 2020, in Andalusia, Spain. Seven facilities implemented an ASP with a bundle of five educational measures (general-ASP) and 7 added one-to-one educational interviews (experimental-ASP). The primary outcome was the overall use of antimicrobials, calculated monthly, as defined daily doses (DDD) per 1000 residents-day (DRD).
Results
During the ASP implementation, the total mean antimicrobial consumption decreased by 31.2% (-16.72 DRD; p = 0.045) with respect to the pre-intervention period; the overall use of quinolones and amoxicillin-clavulanic acid dropped by 52.2% (p = 0.001) and 42.5% (p = 0.006) respectively; and the overall prevalence of MDRO decreased from 24.7% to 17.4% (p = 0.012). During the intervention period, 12.5 educational interviews per doctor were done in the experimental ASP-group; no differences were found in the total mean antimicrobial use between groups (-14.62 DRD; p = 0.25) and two unexpected SARS-CoV-2 waves affected the participating centers with significant increases in the overall mean use of total antimicrobials of 40% (51.56 DRD; p < 0.0001).
Conclusion
This study suggests that an ASP for NHs appears to be associated with a decrease in total consumption of antimicrobials and prevalence of MDRO. This trial did not find benefits associated with educational interviews probably due to the COVID-19 pandemic.
Background
Infection associated with osteosynthesis material (IOM) is one of the most feared and challenging complications of trauma surgery and can cause significant functional loss, requiring multiple interventions and excessive consumption of antimicrobials. Evidence is needed about the best surgical procedure and the duration of antibiotic treatment according to the age of the implant or onset of infection symptoms, as it considers the biofilm formation and the state of fracture healing. There were not clinical trials evaluating the optimal duration of antibiotic therapy in IOM when implant is retained. Because there are antibiotics that have proven to be effective for the treatment of infection associated to implant, mainly in PJI, these antibiotics could be used in these infections. Investigating whether shorter duration of treatment is a priority in infectious diseases, as a way to reduce the exposure to antibiotics and help in controlling antimicrobial resistance and avoiding unnecessary adverse events and cost. We aim to describe the hypothesis, objectives, design, variables and procedures for a pragmatic randomized controlled trial comparing different durations of antibiotic treatment in IOM after long bone fractures treated with debridement and implant retention.
Methods and design
This is a multicenter, open-label, non-inferiority, randomized, controlled, pragmatic phase 3 trial, comparing different durations of antibiotic treatment in IOM after long bone fractures treated with debridement and implant retention. Patients with microbiologically confirmed IOM will be included. Eligible patients are those older than 14 years, with early IOM (up to 2 weeks after the implant surgery) and delayed IOM (between 3 and 10 weeks after the implant surgery) with stabilized fracture and absence of bone exposure who sign the informed consent. Randomization will be 1:1 to receive a short-term antibiotic treatment (8 weeks in early IOM and 12 weeks in delayed IOM) or a long-term antibiotic treatment (12 weeks in early IOM or until fracture healing or implant removal in delayed IOM). The antibiotic treatment will be that used in routine practice by the specialist in infectious diseases. The primary outcome is the composited variable "cure" that includes clinical cure, radiological healing, and definitive soft tissue coverage, which will be evaluated in the test of cure at 12 months after the end of antibiotic therapy. Adverse events, resistance development during therapy and functional status will be collected. A total of 364 patients are needed to show a 10% non-inferiority margin, with 80% power and 5% one-sided significance level.
Discussion
If the hypothesis of non-inferiority of short vs. long antibiotic treatments is demonstrated, and the efficacy of antibiotics with less ecological impact in long treatments, the impact on reduction of bacterial resistance, toxicity and health costs will be observed.
Trial registration
This trial is registered at ClinicalTrials.gov (NCT05294796) on Jan 26th 2022 and at the European Union Drug Regulating Authorities Clinical Trials (EUDRACT) (2021-003914-38) on Jul 16th 2021. The Sponsor Study Code is DURATIOM.
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