Oral versus intravenous antibiotics for bone and joint infection

Ho Kwong Li, Ines Rombach, Rhea Zambellas, A. Sarah Walker, Martin A. McNally, Bridget L. Atkins, Benjamin A. Lipsky, Harriet C. Hughes, Deepa Bose, Michelle Kümin, Claire Scarborough, Philippa C. Matthews, Andrew J. Brent, Jose Lomas, Roger Gundle, Mark Rogers, Adrian Taylor, Brian Angus, Ivor Byren, Anthony R. BerendtSimon Warren, Fiona E. Fitzgerald, Damien J.F. Mack, Susan Hopkins, Jonathan Folb, Helen E. Reynolds, Elinor Moore, Jocelyn Marshall, Neil Jenkins, Christopher E. Moran, Andrew F. Woodhouse, Samantha Stafford, R. Andrew Seaton, Claire Vallance, Carolyn J. Hemsley, Karen Bisnauthsing, Jonathan A.T. Sandoe, Ila Aggarwal, Simon C. Ellis, Deborah J. Bunn, Rebecca K. Sutherland, Gavin Barlow, Cushla Cooper, Claudia Geue, Nicola McMeekin, Andrew H. Briggs, Parham Sendi, Elham Khatamzas, Tri Wangrangsimakul, T. H. Nicholas Wong, Lucinda K. Barrett, Abtin Alvand, C. Fraser Old, Jennifer Bostock, John Paul, Graham Cooke, Guy E. Thwaites, Philip Bejon, Matthew Scarborough

Research output: Contribution to journalArticlepeer-review

345 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)425-436
Number of pages12
JournalNew England Journal of Medicine
Volume380
Issue number5
DOIs
Publication statusPublished - 31 Jan 2019

Bibliographical note

Funding Information:
Supported by the National Institute for Health Research Health Technology Assessment program (project number 11/36/29), the NIHR Imperial College Biomedical Research Centre (to Dr. Cooke), and the NIHR Oxford Biomedical Research Centre (to Drs. Walker, M. Scarborough, and Bejon).

Publisher Copyright:
© 2019 Massachusetts Medical Society.

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