During the 2019 pandemic sweeping through hospitals, an insidious companion emerged in bloodstream infections, where bacteria invade the blood: Staphylococcus aureus with heightened antibiotic resistance. The global rush to treat viral pneumonia often included widespread use of azithromycin, a macrolide antibiotic—a drug class that targets bacterial protein synthesis, raising concerns that this practice may have unintentionally fueled resistance in other pathogens. Amid this crisis, researchers in Rio de Janeiro set out to compare Staphylococcus aureus isolates from before and during the pandemic, seeking to understand how antibiotic prescriptions and bacterial genetics intersected in a high-stakes clinical environment.

Professor Kátia Santos and Professor Raiane Chamon from the Federal University of Rio de Janeiro and the Federal Fluminense University characterized dozens of Staphylococcus aureus isolates recovered from bloodstream infections in the periods before and during the pandemic. The team’s work is published in Scientific Reports, and it reveals both shifts in clonal lineages, or genetic family groups, and striking impacts of prior azithromycin use on resistance patterns.

Overall, nearly half of the isolates were resistant to methicillin, with a small fraction showing limited responsiveness to newer treatments such as ceftaroline and daptomycin, designed to overcome resistance. A widespread hospital-adapted lineage was dominant, constituting around forty percent of the resistant strains, while community-associated genotypes made up almost one-third of all cases. Among patients diagnosed with Coronavirus Disease 2019, methicillin-resistant Staphylococcus aureus, a type of bacteria resistant to common antibiotics, became even more prevalent, affecting the vast majority, compared to less than half of those without the virus. These shifts underscore an alarming rise in multidrug-resistant infections concurrent with the pandemic surge.

Crucially, there was a clear link between azithromycin exposure and elevated resistance rates. “There was a significant impact on the resistance rates for cefoxitin, clindamycin and erythromycin among Staphylococcus aureus isolates from bloodstream infections in COVID‑19 patients and association with the previous use of azithromycin by them,” Professor Santos explained. Isolates from patients who had received azithromycin as outpatients before hospitalization exhibited a marked increase in inducible resistance to macrolides, lincosamides and streptogramins, meaning the bacteria can activate defenses when exposed, suggesting selective pressure from community antibiotic use.

Beyond resistance trends, the genetic landscape of Staphylococcus aureus shifted notably over the study period. The proportion of community‑associated methicillin-resistant Staphylococcus aureus lineages, including strains first identified in community outbreaks in the United States, and generally more virulent, rose during the pandemic, displacing hospital‑adapted clones. “A clonal alternation and an increase in the emergence of community-associated methicillin-resistant Staphylococcus aureus lineages were also found, highlighting the importance of constant microbiological surveillance,” Professor Chamon emphasized, highlighting the dynamic nature of bacterial populations in response to treatment practices.

Drawing on clinical and molecular data, combining patient information and genetic analysis, the research team emphasizes the need for judicious antibiotic stewardship, especially when repurposing drugs in pandemic settings. The surge in methicillin-resistant Staphylococcus aureus among COVID‑19 patients, coupled with the association between azithromycin use and macrolide resistance, serves as a cautionary tale for balancing immediate therapeutic needs against long‑term impacts on antimicrobial efficacy.

Ultimately, Professor Chamon and Professor Santos’s research shows how a viral pandemic can change the bacterial threats in hospitals, speeding up resistance and reshaping the mix of strain types. By linking community antibiotic use to measurable resistance shifts, the research provides actionable insights for infection control teams. As hospitals worldwide prepare for potential future surges, ongoing monitoring and focused antibiotic management will be crucial to prevent the unintended consequences of broad‑spectrum antibiotic use.

Journal Reference

Whitaker C.O., Rocha de Oliveira T.L., Ferreira A.L.P., Nouér S.A., Chamon R.C., dos Santos K.R.N. “Clonal shift and impact of azithromycin use on antimicrobial resistance of Staphylococcus aureus isolated from bloodstream infection during the Coronavirus Disease 2019 pandemic.” Scientific Reports, 2025; 15:597. DOI: https://doi.org/10.1038/s41598-024-84307-1

About the Authors

Dr. Kátia Regina Netto dos Santos is a specialist in Medical Microbiology, working as a Full Professor on the faculty of the Federal University of Rio de Janeiro, in Rio de Janeiro, Brazil. The Professor is a recognized researcher by the National Council for Scientific and Technological Development of Brazil and by the Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro. The Professor has made significant contributions to studies on Staphylococcus aureus and coagulase-negative Staphylococcus, through their molecular and phenotypic diagnosis, molecular detection of antimicrobial resistance and its correlation with conventional techniques, and in aspects related to their virulence and molecular epidemiology. Her study highlights translational medicine, which involves clinical practice and microbiology in health care, developing approaches that can help direct empirical therapies and the rational use of antimicrobials, allowing the transfer of knowledge generated on the bench to clinical practice. Her research has been published in many scientific articles in the medical and microbiology fields. The Professor has supervised numerous undergraduate and postgraduate students, many of whom are now independent researchers at different Universities.

Dr. Raiane Cardoso Chamon holds a degree in Biomedical Sciences from Universidade Federal Fluminense (UFF) (2011), a master’s degree (2013), and a Ph.D. in Sciences (Microbiology) from the Graduate Program of the Institute of Microbiology Prof. Paulo de Góes (IMPG) at the Federal University of Rio de Janeiro (UFRJ). She is an Adjunct Professor of Clinical Microbiology and served as Head of the Department of Pathology at the UFF School of Medicine (2021–2023). Currently, she is the Deputy Head of the same department and is recognized as a “Young Scientist of Our State” by the Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro. Her research focuses on the genotypic and phenotypic characterization of antimicrobial resistance and virulence in Staphylococcus spp. isolates from Antônio Pedro University Hospital, by leading the Staphylococcus research group at UFF.  She is also a permanent faculty member of the Graduate Program in Pathology at UFF. Additionally, she collaborates with the Hospital Infection Laboratory at IMPG–UFRJ on projects involving the characterization and epidemiological and molecular studies of infections caused by Staphylococcus spp. isolates from hospitals in Rio de Janeiro.