Antibiotic Review Kit for Hospitals (ARK-Hospital): a stepped wedge cluster randomised controlled trial

Background: Strategies to reduce antibiotic overuse in hospitals depend on clinicians reviewing antibiotics which have been started empirically. There is a lack of evidence on how to do this effectively. We evaluated a multifaceted behaviour change intervention (ARK) aimed at reducing antibiotic consumption in hospitals by increasing prescriber decisions to stop antibiotics at clinical review. Methods: We performed a stepped-wedge, hospital-level, cluster -randomised controlled trial using computer-generated sequence randomisation of 39 acute hospitals to 7 calendar-time blocks (12/February/2018–01/July/2019). Co-primary outcomes were monthly antibiotic defined-dailydoses (DDD) per acute/medical admission (organisation-level, superiority) and all-cause 30-day mortality (patient-level, non-inferiority, margin 5%). Clusters were eligible if they admitted nonelective medical patients, could identify an intervention “champion” and provide pre-intervention data from February/2016. Sites were followed up for a minimum of 14 months. Intervention effects were assessed using interrupted time series analyses in each cluster. Overall effects were derived through random-effects meta-analysis, using meta-regression to assess heterogeneity in effects across prespecified factors. Trial registration was ISRCTN12674243. Findings: Adjusted estimates showed a year-on-year reduction in antibiotic consumption (-4.8%, 95%CI: -9.1%,-0.2%, p=0.042) following the ARK intervention. Among 7,160,421 acute/medicaladmissions, we observed a -2.7% (95%CI: -5.7%,+0.3%, p=0.079) immediate and +3.0% (95%CI: - 0.1%,+6.2%, p=0.060) sustained change in adjusted 30-day mortality. This mortality trend was not related to the magnitude of antibiotic reduction achieved (Spearman’s ρ=0.011, p=0.949). Whilst 90- day mortality odds appeared to increase over time (+3.9%, 95%CI:+0.5%,+7.4%, p=0.023), this was not observed among admissions before COVID-19 onset (+3.2%, 95%CI:-1.5%,+8.2%, p=0.182). Length of hospital stay was unaffected. Interpretation: The weak, inconsistent effects of the intervention on mortality are likely to be explained by the COVID-19 pandemic onset during the post-implementation phase. We conclude that the ARK-intervention resulted in sustained, safe reductions in hospital antibiotic use

Effects of Antibiotic Cycling Policy on Incidence of Healthcare-Associated MRSA and <em>Clostridioides difficile</em> Infection in Secondary Healthcare Settings

This quasi-experimental study investigated the effect of an antibiotic cycling policy based on time-series analysis of epidemiologic data, which identified antimicrobial drugs and time periods for restriction. Cyclical restrictions of amoxicillin/clavulanic acid, piperacillin/tazobactam, and clarithromycin were undertaken over a 2-year period in the intervention hospital. We used segmented regression analysis to compare the effect on the incidence of healthcare-associated Clostridioides difficile infection (HA-CDI), healthcare-associated methicillin-resistant Staphylococcus aureus (HA-MRSA), and new extended-spectrum β-lactamase (ESBL) isolates and on changes in resistance patterns of the HA-MRSA and ESBL organisms between the intervention and control hospitals. HA-CDI incidence did not change. HA-MRSA incidence increased significantly in the intervention hospital. The resistance of new ESBL isolates to amoxicillin/clavulanic acid and piperacillin/tazobactam decreased significantly in the intervention hospital; however, resistance to piperacillin/tazobactam increased after a return to the standard policy. The results question the value of antibiotic cycling to antibiotic stewardship

Impact of multidisciplinary team escalating approach on antibiotic stewardship in the United Arab Emirates

Antimicrobial stewardship programs (ASP) are an essential strategy to combat antimicrobial resistance. This study aimed to measure the impact of an ASP multidisciplinary team (MDT) escalating intervention on improvement of clinical, microbiological, and other measured outcomes in hospitalised adult patients from medical, intensive care, and burns units. The escalating intervention reviewed the patients’ cases in the intervention group through the clinical pharmacists in the wards and escalated complex cases to ID clinical pharmacist and ID physicians when needed, while only special cases required direct infectious disease (ID) physicians review. Both non-intervention and intervention groups were each followed up for six months. The study involved a total of 3000 patients, with 1340 (45%) representing the intervention group who received a total of 5669 interventions. In the intervention group, a significant reduction in length of hospital stay (p < 0.01), readmission (p < 0.01), and mortality rates (p < 0.01) was observed. Antibiotic use of the WHO AWaRe Reserve group decreased in the intervention group (relative rate change = 0.88). Intravenous to oral antibiotic ratio in the medical ward decreased from 4.8 to 4.1. The presented ASP MDT intervention, utilizing an escalating approach, successfully improved several clinical and other measured outcomes, demonstrating the significant contribution of clinical pharmacists atimproving antibiotic use and informing antimicrobial stewardship

The impact of the COVID-19 pandemic on antibiotic consumption and prevalence of pathogens in primary and secondary healthcare settings in Northern Ireland

To evaluate the impact of the COVID-19 pandemic on the patterns of antimicrobial use and the incidence of pathogens in primary and secondary healthcare settings in Northern Ireland. Data was collected on antibiotic use and Gram-positive and Gram-negative pathogens from primary and secondary healthcare settings in Northern Ireland for the period before (January 2015-March 2020) and during the pandemic (April 2020-December 2021). Time-series intervention analysis methods were utilized. In the hospital setting, the mean total hospital antibiotic consumption during the pandemic was 1864.5 DDD per 1000 occupied bed days (OBD), showing no significant change from pre-pandemic (p=0.7365). During the pandemic: the use of second-generation cephalosporins, third generation cephalosporins, co-amoxiclav, and levofloxacin increased; there was a decrease in the percentage use of hospital Access group (p=0.0083) and an increase in the percentage use of Watch group (p=0.0040); and the number of hospital Klebsiella oxytoca and methicillin-susceptible Staphylococcus aureus cases increased. In primary care the mean total antibiotic consumption during the COVID-19 pandemic was 20.53 DDD per 1000 inhabitants per day (DID), compared to 25.56 DID before the COVID-19 pandemic (p= 0.0071). During the pandemic there was a decrease in use of several antibiotic classes, an increase in the percentage use of the Reserve group (p= 0.0032), and an increase in the number of community onset Pseudomonas aeruginosa cases. This study provides details of both changes in antibiotic consumption and the prevalence of infections in hospitals and primary care before and during the COVID-19 pandemic that emphasise the importance of antimicrobial stewardship in pandemic situations