Doxycycline Compared With Linezolid and Trimethoprim-Sulfamethoxazole for the Treatment of Presumed and Confirmed Gram-Positive Bone and Joint Infections

Background: Several studies have demonstrated comparable treatment outcomes when switching to oral antimicrobial therapy for the treatment of bone and joint infections. The OVIVA trial is the largest of such studies, and used oral agents with high bioavailability: namely fluoroquinolones, clindamycin, and rifampin. A combination of adverse effects, development of resistance during therapy, and potent drug interactions makes these suboptimal choices for gram-positive bone and joint infections. Similarly, tolerability limits the use of other frequently used gram-positive agents: linezolid and trimethoprim/sulfamethoxazole. Comparatively, doxycycline has a favorable adverse effect profile; however, it was infrequently prescribed in OVIVA and other studies. This paucity of data diminishes confidence for its use in bone and joint infections. Methods: This single-center, retrospective cohort study was conducted at a large, urban safety-net hospital from January 2021 to June 2022. Individuals receiving doxycycline were compared with those receiving either linezolid or trimethoprim/sulfamethoxazole following a short course of intravenous therapy. The primary outcome was a composite of the incidence of amputation, operating room debridement, all-cause mortality, and reinitiation of an antibiotic course related to the original bone and joint infection within 9 months. Results: A total of 77 individuals were included in this study (33 doxycycline, 44 linezolid or trimethoprim/sulfamethoxazole). There was no significant difference in the cumulative incidence in the composite primary outcome at 9 months (9 vs. 11, P =0.82). Conclusions: For individuals with presumed or confirmed gram-positive bone and joint infections, doxycycline may represent an acceptable treatment option that is associated with fewer laboratory-related adverse events.