Pandemic Pressure: How Azithromycin Use Shaped Resistance and Clonal Shifts in Staphylococcus aureus

During the COVID-19 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.