LAUSR

Abstract Background Antibiotics (ABX) are frequently inappropriately used to treat nonbacterial causes of respiratory illnesses. The goal of this prospective cohort study was to characterize the impact of ABX used to treat community-acquired pneumonia (CAP) on the fecal microbiome and resistome in healthy volunteers (HV). Methods Twenty HVs were randomized to receive 5 days of levofloxacin (LV), azithromycin (AZ), cefpodoxime (CF), or AZ+CF. Stool was collected before, during, and after ABX, then underwent microbiologic culture and shotgun sequencing. DNA was extracted, then sequenced using the Illumina NextSeq platform. Relative abundance of bacterial taxa was estimated by MetaPhlAn and antibiotic resistance gene (ARG) composition by ShortBRED. Analysis was in R. Results The mean HV age was 37 (range 24–59) and 10 were female. Species diversity measured via Shannon Index and richness were significantly lower in samples taken from all HVs 3 days post-ABX (P < 0.01 for all). While nonmetric multidimensional scaling (NDMS) ordination shows high interpatient dissimilarity (Bray–Curtis) for most samples, the post-ABX intrapatient dissimilarity varies by ABX. The AZ group exhibited chronic alterations in taxa dissimilarity and the CF group had increases in dissimilarity directly post-ABX. The CF+AZ group displayed both acute and persistent perturbations (Figure 1). Although there was no significant change in ARG richness post-ABX, there was a significant increase in overall ARG abundance across all samples (P < 0.003). Within each ABX, there were unique changes in ARG abundance, and groups with CF had increases in ARG abundance (Figure 2). Conclusion ABX used to treat CAP can cause acute microbiome disruptions, as evidenced by decreased microbiome species diversity and richness, and an increase in ARG abundance post-ABX. The duration of this impact is variable. To prevent microbiome disruptions, measures to prevent inappropriate ABX use via ABX stewardship are necessary. Disclosures E. R. Dubberke, Rebiotix: Consultant and Investigator, Consulting fee and Research support. Pfizer: Consultant and Grant Investigator, Consulting fee and Research grant. Synthetic biologics: Consultant, Consulting fee. Merck: Consultant and Investigator, Consulting fee and Research support. Valneva: Consultant, Consulting fee. Achaogen: Consultant, Consulting fee. Alere: webinar, Speaker honorarium. Biofire: webinar, Speaker honorarium.