A time-series analysis approach to quantify change in antibiotic resistance and antibiotic consumption during COVID-19 Epidemics: a multicenter cross-national ecological study on behalf of QUARANTINE (QUantifying change in Antibiotic Resistance, ANTibiotic use, and INfection control during COVID-19 Epidemics) study project

Objectives: We aim to assess the impact of COVID-19 on antibiotic consumption (AMC) and antimicrobial-resistance (AMR) in the new epidemiological scenario from a cross-national perspective. Methods: A quasi-experimental retrospective multicenter ecological study was conducted to explore the impact of COVID-19 on AMC and AMR using routinely generated retrospectively time series data. This study included nine Healthcare University Hospitals from Europe and Israel on behalf of QUARANTINE project. Total effects were defined as the difference between the pre-COVID-19 period (ranging from January 2015 or January 2016 to February 2020) and during the COVID-19 pandemic period (March 2020 to July 2021 or December 2021. The outcomes were incidence density (ID) of carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumoniae (CRKP), extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli, vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Pseudomonas aeruginosa (CRPA) and Clostridiodies difficile, as monthly isolates per 1000 patient days (PD) and the monthly AMC ranked according to the Access, Watch, and Reserve (AWaRe) WHO classification system. Results: We assessed 15.9 million total hospital bed-days, 315,736 COVID-19 bed-days, 52,557 monthly bacterial isolates, and 461,739 monthly antimicrobial DDDs. The COVID-19 pandemic had a significant impact on the consumption of overall hospital antibiotics combined in all centers except two. Prescriptions for piperacillin/tazobactam, glycopeptides, and ceftazidime/avibactam increased, while third-generation cephalosporins, macrolides, and fluoroquinolones returned to pre-pandemic levels after an initial surge, in all centres. A positive relationship between the pandemic intensity and VRE ID was observed in 6/9 (66%) centres followed by MRSA-ID and CRPA-ID 3/4 (44%) for both. A negative relationship was found for ESBL-producing E. coli ID. Conclusions: The COVID-19 pandemic was associated with higher usage of broad-spectrum antibiotics and higher incidence of multi-drug-resistant bacteria, with great variability by Countries. These results could support international action plans that embed AMR as a priority in the post- COVID-19 era.