Oral versus Intravenous Antibiotics for Bone and Joint Infection

Background

Complex bone and joint infections were long managed with surgery plus a prolonged course of intravenous antibiotics, a habit rooted in a widely cited review from decades ago that declared osteomyelitis was rarely controlled without weeks of parenteral therapy. But intravenous therapy brings catheter risks, inconvenience, and higher cost, and earlier comparative evidence was too thin to change practice. OVIVA was designed to test, pragmatically, whether oral antibiotics could replace intravenous therapy during the first weeks of treatment without losing effectiveness.

Methods

“In the analysis of the risk of the primary end point, the noninferiority margin was 7.5 percentage points.” Noninferiority was met if the upper limit of the two-sided 90% CI for the risk difference (oral minus intravenous) fell below 7.5 percentage points.

Results

Among the 1054 participants (527 per group), end-point data were available for 96.3%; missing data (3.7%) were imputed. Definite treatment failure occurred in 13.2% of the oral group versus 14.6% of the intravenous group — the intention-to-treat difference was −1.4 percentage points (90% CI −4.9 to 2.2; 95% CI −5.6 to 2.9), meeting noninferiority against the 7.5-percentage-point margin (after an earlier 5-percentage-point margin was judged too restrictive).

“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.” — the paper

Serious adverse events were similar (27.7% intravenous vs 26.2% oral; P=0.58), catheter complications favored the oral strategy (9.4% vs 1.0%), early discontinuation was less common with oral therapy (12.8% vs 18.9%; P=0.006), and C. difficile-associated diarrhea was comparable (1.7% vs 1.0%; P=0.30). Median hospital stay was shorter with the oral strategy (11 vs 14 days), and total treatment duration did not differ (71 vs 78 days; P=0.63).

Conclusions

In OVIVA, 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. The authors note that the results challenge a widely accepted standard of care, and that oral therapy was associated with shorter hospital stays and fewer complications than intravenous therapy.

Limitations

The trial was necessarily open-label, because exposing participants to 6 weeks of intravenous placebo would have been unethical; objective end points and blinded adjudication minimized potential bias. Follow-up lasted 1 year, so later treatment failures cannot be ruled out. Attribution of some serious adverse events was subjective. Oral therapy may not be appropriate for every patient, for example those with poor enteral absorption or pathogens resistant to oral agents.

What changed in practice

OVIVA supports oral antibiotic therapy for appropriately selected patients with bone and joint infection, delivering the same 1-year failure risk with shorter hospital stays and fewer catheter complications. It challenged the long-held default to intravenous therapy and, in the authors' words, helps “challenge a widely accepted standard of care”. Choosing and monitoring the oral regimen still requires an infection specialist.