In the JournalsPerspective

OVIVA: Oral therapy noninferior to IV therapy for bone and joint infections

Oral antibiotic therapy is noninferior to IV antibiotic therapy when used in the first 6 weeks of treatment for complex bone and joint infections, according to results from OVIVA, a randomized controlled trial.

The findings, published today in The New England Journal of Medicine, “challenge a widely accepted standard of care,” noted Ho-Kwong Li, MRCP, from the Oxford University Hospitals NHS Foundation Trust, and colleagues.

“Complex bone and joint infections are typically managed with surgery and a prolonged course of treatment with intravenous antibiotic agents,” they wrote. “The preference for intravenous antibiotics reflects a broadly held belief that parenteral therapy is inherently superior to oral therapy, a view supported by an influential 1970 article that suggested that ‘... osteomyelitis is rarely controlled without the combination of careful, complete surgical debridement and prolonged (4 to 6 weeks) parenteral antibiotic therapy ... .’ However, intravenous therapy is associated with substantial risks, inconvenience, and higher costs than oral therapy.”

In OVIVA, Li and colleagues enrolled 1,054 adults being treated for bone or joint infections at 26 health centers in the United Kingdom and randomly assigned them evenly to receive oral or IV antibiotics within 7 days after surgery — or 7 days after the start of antibiotic treatment if surgery was not needed — to complete the first 6 weeks of therapy. The primary endpoint was definitive treatment failure within 1 year, and the noninferiority margin was 7.5 percentage points.

According to the findings, treatment failure occurred in 14.6% of participants in the IV group compared with 13.2% in patients who received oral antibiotics. In an intent-to-treat analysis, the researchers reported observing a –1.4 percentage point (90% CI, –4.9 to 2.2; 95% CI, –5.6 to 2.9) difference in the risk for definitive treatment failure between the oral vs. IV groups. This indicated noninferiority, a finding supported by complete-case, per-protocol and sensitivity analyses, Li and colleagues said.

According to the study, no significant difference in the incidence of serious adverse events was observed between the groups. Some 9.3% of participants in the IV group had catheter complications compared with 1% in the oral group.

“We found that appropriately selected oral antibiotic therapy was noninferior to intravenous therapy when used during the first 6 weeks in the management of bone and joint infection, as assessed by treatment failure within 1 year,” Li and colleagues concluded. “Oral antibiotic therapy was associated with a shorter length of hospital stay and with fewer complications than intravenous therapy.” – by Marley Ghizzone

Disclosures: Li reports receiving grants from the National Institute for Health Research Health Technology Assessment during the conduct of the study. Please see the study for all other authors’ relevant financial disclosures.

Oral antibiotic therapy is noninferior to IV antibiotic therapy when used in the first 6 weeks of treatment for complex bone and joint infections, according to results from OVIVA, a randomized controlled trial.

The findings, published today in The New England Journal of Medicine, “challenge a widely accepted standard of care,” noted Ho-Kwong Li, MRCP, from the Oxford University Hospitals NHS Foundation Trust, and colleagues.

“Complex bone and joint infections are typically managed with surgery and a prolonged course of treatment with intravenous antibiotic agents,” they wrote. “The preference for intravenous antibiotics reflects a broadly held belief that parenteral therapy is inherently superior to oral therapy, a view supported by an influential 1970 article that suggested that ‘... osteomyelitis is rarely controlled without the combination of careful, complete surgical debridement and prolonged (4 to 6 weeks) parenteral antibiotic therapy ... .’ However, intravenous therapy is associated with substantial risks, inconvenience, and higher costs than oral therapy.”

In OVIVA, Li and colleagues enrolled 1,054 adults being treated for bone or joint infections at 26 health centers in the United Kingdom and randomly assigned them evenly to receive oral or IV antibiotics within 7 days after surgery — or 7 days after the start of antibiotic treatment if surgery was not needed — to complete the first 6 weeks of therapy. The primary endpoint was definitive treatment failure within 1 year, and the noninferiority margin was 7.5 percentage points.

According to the findings, treatment failure occurred in 14.6% of participants in the IV group compared with 13.2% in patients who received oral antibiotics. In an intent-to-treat analysis, the researchers reported observing a –1.4 percentage point (90% CI, –4.9 to 2.2; 95% CI, –5.6 to 2.9) difference in the risk for definitive treatment failure between the oral vs. IV groups. This indicated noninferiority, a finding supported by complete-case, per-protocol and sensitivity analyses, Li and colleagues said.

According to the study, no significant difference in the incidence of serious adverse events was observed between the groups. Some 9.3% of participants in the IV group had catheter complications compared with 1% in the oral group.

“We found that appropriately selected oral antibiotic therapy was noninferior to intravenous therapy when used during the first 6 weeks in the management of bone and joint infection, as assessed by treatment failure within 1 year,” Li and colleagues concluded. “Oral antibiotic therapy was associated with a shorter length of hospital stay and with fewer complications than intravenous therapy.” – by Marley Ghizzone

Disclosures: Li reports receiving grants from the National Institute for Health Research Health Technology Assessment during the conduct of the study. Please see the study for all other authors’ relevant financial disclosures.

    Perspective

    andrej Spec, MD, MSCI

    The main message is that once the infection is under control with IV antibiotics, there is no reason to continue IV therapy in many cases. This will significantly simplify the care of many patients with osteomyelitis.
    Also, this will significantly decrease how often IV antibiotics are used outside of the hospital, the so-called outpatient parenteral antibiotic therapy (OPAT). In many complicated cases that were excluded from the study, we will still continue to use OPAT, but this study will make many physicians feel a lot more comfortable with the transition to oral therapy.
    In infectious disease, we desperately need more studies like this. Public funding is scarce for clinical studies, and that forces us often to rely on retrospective data and studies performed by pharmaceutical companies. We need to improve our funding management so that we publish a few landmark, practice-changing studies like this one each year. This study and others, like the POET trial, show how much of an audience exists for these kinds of trials.

    Andrej Spec, MD, MSCI

    Assistant professor of medicine
    Associate director, Infectious Disease Clinical Research Unit
    Washington University School of Medicine
    St. Louis

    Disclosure: Spec reports no relevant financial disclosures.

    –	Gregory D. Schroeder, MD

    This is an outstanding article by Li and colleagues, and the authors and study participants should be commended. The results are clear that in some patients with orthopaedic infections, oral antibiotics are as effective as IV antibiotics with fewer complications. However, it is critical that orthopedic surgeons and infectious disease physicians approach each case individually. This article groups all orthopedic infections together, and this heterogeneity is clearly the biggest limitation of the study. While its broad inclusion criteria allow for generalizability, this also means there are undoubtedly certain cases for which results of the study are not true. Reading the article as an orthopedic spine surgeon, I find it challenging to extrapolate the results of the current patients to many of my patients with osteodiscitis. Only 39 total patients had surgery for discitis, spinal osteomyelitis or an epidural abscess. Furthermore, it is not clear to me what type of surgery for discitis, spinal osteomyelitis or epidural abscess would be performed without a debridement. Given the catastrophic neurologic events that can occur from inadequately treated osteodiscitis, and the fact that the intervertebral disc is a relatively avascular structure, this article is unlikely to change my practice in the treatment of osteodiscitis. Conversely, in patients with an acute postoperative infection, a trial of oral antibiotics may be prudent before moving forward with more aggressive therapy.

    Gregory D. Schroeder, MD

    Department of orthopedic surgery
    Rothman Orthopaedic Specialty Hospital
    Assistant professor of orthopaedic surgery
    Thomas Jefferson University
    Philadelphia

    Disclosure: Schroeder reports no relevant financial disclosures.