Oral versus Intravenous Antibiotics for Bone and Joint Infection.
Li H-K., Rombach I., Zambellas R., Walker AS., McNally MA., Atkins BL., Lipsky BA., Hughes HC., Bose D., Kümin M., Scarborough C., Matthews PC., Brent AJ., Lomas J., Gundle R., Rogers M., Taylor A., Angus B., Byren I., Berendt AR., Warren S., Fitzgerald FE., Mack DJF., Hopkins S., Folb J., Reynolds HE., Moore E., Marshall J., Jenkins N., Moran CE., Woodhouse AF., Stafford S., Seaton RA., Vallance C., Hemsley CJ., Bisnauthsing K., Sandoe JAT., Aggarwal I., Ellis SC., Bunn DJ., Sutherland RK., Barlow G., Cooper C., Geue C., McMeekin N., Briggs AH., Sendi P., Khatamzas E., Wangrangsimakul T., Wong THN., Barrett LK., Alvand A., Old CF., Bostock J., Paul J., Cooke G., Thwaites GE., Bejon P., Scarborough M., OVIVA Trial Collaborators None.
BACKGROUND: The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication. METHODS: We enrolled adults who were being treated for bone or joint infection at 26 U.K. centers. Within 7 days after surgery (or, if the infection was being managed without surgery, within 7 days after the start of antibiotic treatment), participants were randomly assigned to receive either intravenous or oral antibiotics to complete the first 6 weeks of therapy. Follow-on oral antibiotics were permitted in both groups. The primary end point was definitive treatment failure within 1 year after randomization. In the analysis of the risk of the primary end point, the noninferiority margin was 7.5 percentage points. RESULTS: Among the 1054 participants (527 in each group), end-point data were available for 1015 (96.3%). Treatment failure occurred in 74 of 506 participants (14.6%) in the intravenous group and 67 of 509 participants (13.2%) in the oral group. Missing end-point data (39 participants, 3.7%) were imputed. The intention-to-treat analysis showed a difference in the risk of definitive treatment failure (oral group vs. intravenous group) of -1.4 percentage points (90% confidence interval [CI], -4.9 to 2.2; 95% CI, -5.6 to 2.9), indicating noninferiority. Complete-case, per-protocol, and sensitivity analyses supported this result. The between-group difference in the incidence of serious adverse events was not significant (146 of 527 participants [27.7%] in the intravenous group and 138 of 527 [26.2%] in the oral group; P=0.58). Catheter complications, analyzed as a secondary end point, were more common in the intravenous group (9.4% vs. 1.0%). CONCLUSIONS: Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year. (Funded by the National Institute for Health Research; OVIVA Current Controlled Trials number, ISRCTN91566927 .).