Oral versus intravenous antibiotics for bone and joint infection

Li, H.-K. et al. (2019) Oral versus intravenous antibiotics for bone and joint infection. New England Journal of Medicine, 380(5), pp. 425-436. (doi: 10.1056/NEJMoa1710926) (PMID:30699315)

Abstract

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.)

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Mcmeekin, Dr Nicola and Geue, Dr Claudia and Briggs, Professor Andrew
• Authors: Li, H.-K., Rombach, I., Zambellas, R., Walker, S., McNally, M. A., Atkins, B. L., Lipsky, B. A., Hughes, H. C., Bose, D., Kümin, M., Scarborough, C., Matthews, P. C., Brent, A. J., Lomas, J., Gundle, R., Rogers, M., Taylor, A., Angus, B., Byren, I., Berendt, A. R., Warren, S., Fitzgerald, F. E., Mack, D. J.F., Hopkins, S., Folb, J., Reynolds, H. E., Moore, E., Marshall, J., Jenkins, N., Moran, C. E., Woodhouse, A. F., Stafford, S., Seaton, R. A., Vallance, C., Hemsley, C. J., Bisnauthsing, K., Sandoe, J. A.T., Aggarwal, I., Ellis, S. C., Bunn, D. J., Sutherland, R. K., Barlow, G., Cooper, C., Geue, C., Mcmeekin, N., Briggs, A. H., Sendi, P., Khatamzas, E., Wangrangsimakul, T., Wong, T.H. N., Barrett, L. K., Alvand, A., Old, C. F., Bostock, J., Paul, J., Cooke, G., Thwaites, G. E., Bejon, P., and Scarborough, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Health Economics and Health Technology Assessment
• Journal Name: New England Journal of Medicine
• Publisher: Massachusetts Medical Society
• ISSN: 0028-4793
• ISSN (Online): 1533-4406
• Copyright Holders: Copyright © 2019 Massachusetts Medical Society
• First Published: First published in New England Journal of Medicine 380(5):425-436
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher