RCT: In bone and joint infections, oral antibiotic therapy was noninferior to IV antibiotic therapy for treatment failure at 1 year.
Li HK, Rombach I, Zambellas R, et al. Oral versus Intravenous Antibiotics for Bone and Joint Infection. N Engl J Med. 2019 Jan 31;380(5):425-436. doi: 10.1056/NEJMoa1710926.

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 .).

Ratings
Specialty Area Score
Hospital Doctor/Hospitalists
Internal Medicine
Infectious Disease
Comments from MORE raters

Hospital Doctor/Hospitalists

As the authors of the editorial comment, it is probably too early to change practice, but confirmation would have a huge impact on treatment of these infections with large cost savings.

This article reveals a potential opportunity for a paradigm shift in management of orthopedic infections that will be manifest in reduced cost of care and potentially fewer direct and indirect complications of care. I will be interested to see the feedback from this data from ID and Orthopedic colleagues.

As a practicing hospitalist consultant, this article provides adequate evidence to allow for conversations between ID specialists to utilize oral antibiotics instead of IV antibiotics for patients with osteomyelitis with high likelihood of treatment completion.

Infectious Disease

This randomized comparison of IV vs PO therapy for bone and joint infection, 60.6% with prosthesis-related infection, showed non-inferiority of PO therapy vs IV therapy; 13.2% failure with oral therapy and 14.6% failure with intravenous therapy. The accompanying editorial claims victory, but this is not ready for prime time. The devil is in the details: only one-year follow-up, open label study. Kudos for inclusiveness: with and without surgery, heterogeneous population, and regimens. However, we are unable to discern what characteristics would best define patients likely to benefit from PO vs IV regimens. Most patients received therapy beyond 6 weeks, median duration 78 days in the IV group and 71 days in the PO group. Most disconcerting is the obvious selection of participants - 2077 patients were screened and only 1054 randomized. The complication rate was similar in both groups, signifying the need for close follow-up with oral regimens. Only 3-day difference in length-of-stay.

Internal Medicine

This issue is not really common but it is common enough in primary care that this is something primary care physcians should know about. If you can get away without having to place a PICC line, that's a good thing.

In this non-inferiority trial, 1054 real-world patients with bone and joint infections (including 23% with prosthetic retained implants) who normally would have received IV antibiotics for 6 weeks were randomized to oral or IV antibiotics. Most the patients (81%) had a lower limb infection, with around a quarter with hip, knee, and foot infections. They included patients on immunosuppressives (4.3%) and HIV (0.4%). S. aureus was the most commonly isolated bug (37%, including 10% MRSA), but those initially S. aureus bacteremic were excluded. Greater than 90% had 95% compliance or better with oral meds. Both groups had similar rates of treatment failure (14.6% IV, 13.2% oral) with no difference in C. difficile rates. In US practice, where extended antibiotics mean an ECF or significant out-of-pocket cost for home antibiotics, this is a significant and important study that probably bears repeating before guidelines change.

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