Impacts of the COVID-19 pandemic on antibiotic use and resistance in hospitals: a retrospective ecological analysis of French national surveillance data over 2019-2022

SummaryO_ST_ABSBackgroundC_ST_ABSThe COVID-19 pandemic led to major disruptions in healthcare services at the hospital and community levels. The resulting impact on antibiotic resistance (ABR) in hospitals is difficult to predict. MethodsWe exploited data from the French national surveillance system over four years (2019-2022) including 414 hospitals across 12 French regions. We evaluated changes in annual antibiotic use compared to 2019 using multiple comparison tests. We also compiled a large dataset of 692,551 incident isolates for five antibiotic-bacterium pairs. Using negative binomial regression models accounting for autocorrelation and antibiotic use, we evaluated associations between resistant isolates incidence and COVID-19 indicators (pandemic periods or intubated COVID-19 patient prevalence). We investigated how these associations varied specifically in ICUs (n=85) and across geographical regions. FindingsThe use of some antibiotics, including azithromycin, imipenem and meropenem, significantly increased between 2020 and 2022. Concomitantly, the incidence of methicillin-resistant Staphylococcus aureus (up to 37%, 95% CI: 18-53%) and ESBL-producing Escherichia coli (up to 33%, 95% CI: 16-46%) isolates significantly decreased in hospitals and ICUs during the pandemic. A transient decrease in ICUs was also observed for ESBL-producing Klebsiella pneumoniae during periods of strong anti-COVID-19 interventions in the community (24%, 95% CI: 6-38%). No significant changes for ESBL-producing Enterobacter cloacae complex were observed. Very interestingly, the incidence of carbapenem-resistant Pseudomonas aeruginosa isolates was associated with COVID-19 intubation prevalence in hospitals (p<0.001) and ICUs (p<0.001), notably in the regions most affected by the pandemic. InterpretationOur results highlight strong modifications of antibiotic use and pathogen-specific global impacts of the COVID-19 pandemic on ABR in hospitals. Even though the biological mechanisms underlying between- species differences remain unclear, these results provide important insights into the potential impacts of a viral pandemic on ABR and support the need for pandemic preparedness in healthcare facilities. FundingANR-10-LABX-62-IBEID. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for articles in English published between Jan 1, 2020, and August 31, 2024 exploring national-scale changes in antibiotic resistance (ABR) within healthcare settings during the COVID-19 pandemic. Search terms for titles and abstracts were ("antibiotic resistance" OR "antimicrobial resistance" OR "bacterial resistance" OR "drug resistance" OR "MRSA" OR "ESBL" OR "carbapenem resistant") AND ("hospital" OR "healthcare") AND ("COVID-19" OR "SARS-CoV-2") AND ("national" OR "nationwide"). The search yielded 94 results. We identified 12 relevant studies after filtering out articles referring to viruses, parasites, or fungi, focusing on a single hospital, evaluating changes in antibiotic use only, assessing healthcare workers practices, or using qualitative approaches. All studies used either national surveillance data on antibiotic resistance or large multi-center cohorts of inpatients. Five studies showed a significant increase in MRSA, at least during the first wave of the COVID-19 pandemic, while two studies did not find changes at the national level compared to 2019. Interestingly, one study showed that the abandonment of infection prevention and control strategies that specifically target hospital-acquired MRSA infections was associated with an increase of these infections, regardless of COVID-19 admission prevalence. One study in Spain showed decreased resistance of P. aeruginosa to all tested antibiotics in 2022 compared to 2017, using point prevalence survey results. Conversely, one study focusing on US Veterans Affairs hospitals showed increased incidence and resistance of healthcare-associated carbapenem-resistant P. aeruginosa (CR-PA) infections during the pandemic. Most studies used univariate statistical approaches. Only two studies included COVID-19-related variables in their models; they found no association with MRSA or extended-spectrum cephalosporin-resistant E. coli and K. pneumoniae. Added value of this studyHere, we provide the first evaluation of the impact of the pandemic on antibiotic consumption and resistance for five antibiotic-bacterium pairs (MRSA, CR-PA, ESBL-producing E. coli, ESBL-producing K. pneumoniae, and ESBL-producing E. cloacae complex) in hospitals, at the national and regional scales. By analyzing French surveillance data from the SPARES database including 414 hospitals that represent up to 14% of French hospitals, we evaluated annual changes in antibiotic use and quantified the impacts at the weekly level of the COVID-19 pandemic on the incidence of five of the most prevalent resistant bacteria in France. Accounting for autocorrelation and antibiotic use, factors that were not considered in previous studies, we report a significant positive association between the weekly incidence of CR-PA isolates and the prevalence of intubated COVID-19 patients in the preceding weeks. Carbapenem use and intubation being risk factors of CR-PA infections, our results suggest a direct impact of the pandemic on CR-PA epidemiology. Inversely, we show that the incidence of ESBL-producing E. coli and MRSA isolates decreased after the start of the first pandemic wave at the hospital level but also in ICUs. The fine grain analysis across 12 French administrative regions revealed regional heterogeneities, but highlighted consistent associations in the regions most affected by the COVID-19 pandemic. Implications of all the available evidencePandemics not only destabilize healthcare systems by adding pressure and changing healthcare worker behaviors, but also influence the epidemiology of other infectious diseases as shown in our study. We specifically highlight the contrasting effects of the COVID-19 pandemic on ABR in French hospitals, associated with an increase in CR-PA isolate incidence but a general decrease in ESBL-producing E. coli and MRSA. This work highlights how national-scale hospital surveillance systems such as SPARES that collect data at the weekly level are key to capture the evolving impacts of pandemics. They also allow to generate hypotheses on the potential mechanisms of action of the pandemic on ABR epidemiology, as showcased by the analysis of CR-PA isolates incidence, and thereby participate in the improvement of healthcare systems in pandemic context.