SLR - May 2019 - Tyler Reber

Oral Versus Intravenous Antibiotic Treatment for Bone and Joint Infections (OVIVA): Study Protocol for a Randomized Controlled Trial

Reference: Li HK, 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. Oral Versus Intravenous Antibiotic Treatment for Bone and Joint Infections (OVIVA): Study Protocol for a Randomized Controlled Trial. N Engl J Med. 2019 Jan 31;380(5):425–436.

Scientific Literature Review

Reviewed By: Tyler Reber, DPM
Residency Program: CHI Franciscan Foot and Ankle Institute, Federal Way, WA

Podiatric Relevance: Osteomyelitis and septic arthritis are increasing in their frequency of treatment by podiatric surgeons with the rise in diabetes and joint replacements. The current standard of care is surgical treatment with prolonged intravenous (IV) antibiotics or, in certain circumstances, IV antibiotics alone. This study compared the effectiveness of oral versus IV antibiotics for acute and chronic osteomyelitis, native and prosthetic joint infections and orthopaedic hardware infections throughout the body to analyze if oral antibiotics are inferior to IV antibiotic treatment.

Methods: The study was a level I randomized, controlled, noninferiority trial conducted at 26 hospitals across the United Kingdom (UK). Eligible participants were >18 years old with symptoms of bone or joint infection that were randomized into groups of six weeks or more of IV or oral antibiotic treatment within seven days of the onset of infection for infections treated nonsurgically and within seven days of definitive surgical treatment if surgical intervention was necessary. The primary outcome measure was definite treatment failure within one year of starting antibiotic therapy defined as continued presence of infection, including draining sinus tracts, pus, or histologic or microbiologic evidence of infection. Some of the secondary endpoints included length of hospital stay, duration of antibiotic treatment and complications involved with the IV catheter.

Results: One thousand fifty patients participated in the study, and endpoint data was available for 1,015. Treatment failure occurred in 14.6 percent in the intravenous group compared to 13.2 percent in the oral group, which was not statistically significant. Secondary endpoint data showed median hospital length of stay was significantly longer in the IV group (14 days) compared to the oral group (11 days). There was no significant difference in the duration of antibiotic therapy with an average of 78 days in the IV group and 71 days in the oral group. Complications associated with the intravenous catheter occurred in 9.4 percent of the IV group versus only 1.0 percent in the oral group.

Conclusion: This study challenges the widely accepted, but somewhat unsupported, standard of care that IV antibiotics are superior to oral antibiotics in treating infections commonly encountered by orthopaedic and podiatric surgeons. The results from this study show that at these facilities, oral antibiotics were as effective as IV antibiotics in treating osteomyelitis, septic arthritis and hardware infections throughout the body. The authors recommend selecting an appropriate antibiotic with high bioavailability and tissue penetrance when taken orally. The protocols used in this study were not strict, and some of the oral antibiotic-treated patients at some point received IV antibiotics throughout their treatment course, while some of the IV antibiotic group received oral rifampin. Not all patients completed a six-week course of antibiotics, and some patients from both groups continued oral antibiotics after six weeks. These limitations in protocol must be taken into consideration when interpreting the results. Although this study is not specific to the lower extremity, it shows evidence that oral antibiotics may be used in lieu of IV treatment when an appropriate oral antibiotic is available.  

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