Changes in the Gut Microbiome Following Perioperative Prophylactic Cefazolin Administration in Patients Undergoing Orthopedic Surgery: A Longitudinal Prospective Study

Introduction: Cefazolin is a first-generation cephalosporin with a moderate antimicrobial spectrum and the ability to induce the production of beta-lactamases by bacterial hosts. We investigated the effect of prophylactic cefazolin administration on the gut microbiome in patients undergoing orthopedic surgery. Methods: A total of 42 patients were included in this study, and fecal samples were collected before cefazolin administration, within 3 days after administration, and 1 month after surgery. Shotgun whole-metagenome sequencing was performed with DNA extracted from fecal samples to assess the taxonomic composition and antimicrobial resistance genes (ARGs). Results: Within 3 days after perioperative prophylactic cefazolin administration, both the diversity indices and the Gut Microbiome Health Index were significantly decreased. Furthermore, a decrease in two beneficial anaerobic Gram-positive taxa, Ruminococcus and Fusicatenibacter, and an increase in Enterobacterales was observed. The relative abundances of ARGs related to fluoroquinolone and beta-lactam antimicrobials including penicillin, cephalosporin, carbapenem, and monobactam, were also significantly increased. The changes in the taxonomic composition and resistome related to perioperative cefazolin administration partially reverted after one month. Conclusions: Our findings suggest that even perioperative administration of a single-class antimicrobial agent could be related to the decrease of the gut microbiome diversity with potentially unfavorable taxonomic changes and lead to an increase in ARGs.