Oral Antibiotics Non-Inferior to IV Antibiotics for Orthopedic Infections in OVIVA Trial


Although IV antibiotics have been the standard of care for bone and joint infections, a new study finds that oral antibiotics were non-inferior.

A new study suggests that oral antibiotic therapy may be appropriate for treating bone and joint infections typically treated with a prolonged course of intravenous (IV) antibiotic therapy.

The new paper published in the New England Journal of Medicine details the Oral Versus Intravenous Antibiotics for Bone and Joint Infection (OVIVA) trial, in which investigators aimed to determine whether oral antibiotics are non-inferior to IV antibiotics in the management of complex orthopedic infections. Such infections can occur after joint replacement surgery and other implant-associated procedures. The current standard of care for bone and joint infections typically includes surgery followed by a 4- to 6-week course of IV antibiotics, although the authors note there is little evidence to suggest that oral antibiotic therapy leads to worse outcomes.

To evaluate outcomes at 1 year after intravenous therapy as compared with oral therapy administered during the initial 6 weeks of treatment for orthopedic infection, the investigators conducted a multicenter, open label, parallel-group, randomized, controlled noninferiority trial comparing IV versus oral antibiotic therapy in participants older than 18 years of age with serious bone and joint infections. Investigators did not use blinding due to ethical considerations of exposing trial participants in the oral group to the risks associated with prolonged courses of intravenously administered placebo.

Patients from 26 hospitals in the United Kingdom were enrolled in the trial and were randomly assigned 6 weeks of either standard IV therapy or oral antibiotics on a 1:1 basis within 7 days after surgery, or 7 days following initiation of antibiotic treatment if there was no surgery. A total of 1054 patients were enrolled in the study (527 in each treatment group), of whom 639 (60.1%) had metalware-related infections. Staphylococcus aureus, coagulase negative Staphylococcus, and Streptococcus species were the most commonly identified organisms.

Investigators collected endpoint data from 1015 trial participants and found that, at 1-year follow up, 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. The intention-to-treat analysis showed a difference in the risk of definitive treatment failure (oral vs IV) of -1.4 percentage points (90% confidence interval [CI], -4.9 to 2.2; 95% CI, -5.6 to 2.9), indicating noninferiority, results which were consistent across all subgroups analyzed.

“In this trial, with regard to treatment failure assessed at 1 year, oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks of treatment for bone and joint infection,” study investigators wrote, noting that oral antibiotic therapy was associated with shorter hospital stays and fewer complications than IV therapy, and that oral therapy may not be appropriate for some patients and pathogens with resistance to oral agents. “Our results thereby challenge a widely accepted standard of care.”

The OVIVA trial did not compare specific antibiotic agents or stipulate which agents should be used. Instead, investigators relied on a consulting infectious-disease specialist to select and adjust antibiotic regimens with consideration to factors such as susceptibilities, bioavailability, tissue penetration, side effects, coexisting conditions, and drug interactions. The trial was funded by the UK’s National Institute for Health Research.

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