Empiric azithromycin alters the upper respiratory microbiome and resistome without anti-inflammatory benefit in COVID-19Original paper
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease, four years before the first published case study.
Read MoreWhat was studied?
This study tested how empiric azithromycin affects the respiratory microbiome and resistome during COVID-19. Azithromycin was widely given to hospitalized COVID-19 patients despite trials showing no clinical benefit. Researchers applied longitudinal metatranscriptomics to nasal swabs collected over 28 days. They profiled the microbiome, antimicrobial resistance genes, and host immune gene expression in blood and airway. They compared azithromycin recipients with patients given no antibiotics or other antibiotics.
Who was studied?
The cohort was 1,164 adults hospitalized for COVID-19 across 20 US hospitals in the IMPACC study, enrolled from May 2020 to March 2021. None were vaccinated at enrollment. Of these, 366 (31.4 percent) received azithromycin, 474 (40.7 percent) received no antibiotics, and 324 (27.8 percent) received other antibiotics. The median azithromycin course was 2 days. Patients were grouped into five COVID-19 severity trajectory groups, and azithromycin use was highest in the most severe patients.
What were the most important findings?
Azithromycin reduced airway bacterial relative abundance within about one day (fold change 0.90) and shifted community composition (PERMANOVA p equal to 0.001). It enriched potentially pathogenic taxa and depleted commensals. Macrolide, lincosamide, and streptogramin (MLS) resistance genes rose sharply. Their share of the resistome climbed from 24.5 to 42.9 percent after 5 days, and enrichment persisted 7 to 10 days after the drug stopped. There were no differences in host inflammatory gene expression in blood or airway, and no change in SARS-CoV-2 abundance.
What are the greatest implications of this study?
The findings show empiric azithromycin during viral respiratory infection drives macrolide resistance without any measurable anti-inflammatory or antiviral benefit. Effects began within days and outlasted the treatment course. This reinforces antibiotic stewardship, since inappropriate macrolide use can expand resistance in commensals and potential pathogens. The authors note the observational design and nasal-swab sampling as limits, and call for randomized trials with airway, gut, and culture sampling.