A Look at the Evidence: Should Orthopaedic Surgeons Start Prescribing 6 Weeks of Oral Antibiotics?

The current standard of care for bone infections at most centers is 6 weeks of IV antibiotics. However, in recent years, this practice has been called into question to reduce healthcare costs, improve antibiotic stewardship, and reduce IV antibiotic complications such as Clostridium difficile, deep vein thrombosis, line clotting, and sepsis. This article presents the current evidence for oral versus IV antibiotics.

In 2019, Helen Boucher, MD, an infectious diseases specialist at Tufts University, authored an editorial in the New England Journal of Medicine titled “Partial Oral Therapy for Osteomyelitis and Endocarditis—Is It Time?” The theme of the editorial was how and why the medical community should combat antimicrobial resistance. For example, she cited that an estimated 162,000 deaths per year in the United States are the result of multidrug-resistant infections. Dr. Boucher wrote, “Surveillance and stewardship [happen] through the use of narrow-spectrum therapy, shorter durations of therapy, and oral rather than parenteral therapy.” Considering oral therapy rather than IV therapy is one way the orthopaedic community can impact the development of multidrug-resistant infections.

Efficacy of oral antibiotics
The Oral versus IV Antibiotics (OVIVA) study was a randomized, controlled trial, published in 2019, that enrolled more than 1,000 participants with bone or joint infection (e.g., periprosthetic joint infection, fracture-related infection) across 26 centers in the United Kingdom. Participants were randomly assigned to receive either IV or oral antibiotics to complete the first 6 weeks of therapy, which commenced within 7 days of either surgical treatment or antibiotic therapy for osteomyelitis. The primary endpoint was definitive treatment failure within 1 year after randomization. Treatment failure occurred in 74 of 506 participants (14.6 percent) in the IV group and 67 of 509 participants (13.2 percent) in the oral group. The authors concluded that oral antibiotic therapy is noninferior to IV therapy when used during the first 6 weeks of treatment for bone or joint infection in regard to the primary endpoint. Furthermore, these findings challenge the current standard of care and provide an opportunity to realize significant benefits for patients, antimicrobial stewardship, and the healthcare economy.

A U.S.-based multicenter study from William T. Obremskey, MD, MPH, and colleagues, published in 2017 in the Journal of Orthopaedic Trauma, also compared oral and IV antibiotics in patients with postoperative wound infections after extremity fractures. That study also showed that oral antibiotics were noninferior to IV antibiotic regimens. The authors had these words of caution: “A limitation of the study is lack of blinding of clinicians and patients. Other limitations include those typical of pragmatic trials in that the details of surgical treatment were left to the discretion of the site surgeons, which might lead to important variations in treatment that might harm the ability to detect a treatment effect. However, this design should also increase the generalizability of the findings.” In other words, despite the surgical treatments being left to the discretion of the site surgeons, which is an inherent limiting study variable, the variability likely reflects practice patterns outside the study. So, the study limitation described by the authors may actually be a study strength.

Complications and economic impact
How do complication rates and cost benefits compare between oral versus IV 6-week regimens? The data also come from the OVIVA trial. With the exception of IV catheter complications—which occurred in 9.37 percent of the IV arm and 0.96 percent of the oral arm—there were no significant differences between the two arms in the incidence of serious adverse events. Oral therapy was highly cost effective, yielding a saving of £2,740 per patient, without any significant difference in quality-adjusted life-years between the two arms of the trial.

In summary, the common protocol of 6 weeks of IV antibiotics for bone infections has been challenged in recent years by two high-level clinical studies. The benefits of oral versus IV antibiotics include lower costs, improved antibiotic stewardship, and fewer antibiotic side effects. Scant evidence suggests that oral therapy results in worse outcomes than IV antibiotics. Although consultation with an infectious diseases specialist to determine antibiotic treatment remains standard of care, a broad-based switch by clinicians to oral antibiotic regimens is a welcome paradigm change with great potential to reduce the costs, complications, and logistical challenges of discharging patients with 6 weeks of IV antibiotics. The last reason has resulted in a significant reduction of length of stay in the author’s practice.

Daniel R. Schlatterer, DO, MBA, FAAOS, is the former chair of the orthopaedic surgery residency program and former chief of orthopaedic trauma at WellStar Health System in Atlanta, Georgia. He is a member of the AAOS Now Editorial Board.

References

1. Li HK, Rombach I, Zambellas R, et al: Oral versus intravenous antibiotics for bone and joint infection. N Engl J Med 2019;380(5):425-36.
2. Boucher HW: Partial oral therapy for osteomyelitis and endocarditis—is it time? N Engl J Med 2019;380:487-9.
3. McMeekin N, Geue C, Briggs A, et al: Cost-effectiveness of oral versus intravenous antibiotics (OVIVA) in patients with bone and joint infection: evidence from a non-inferiority trial. Wellcome Open Res 2019;4:108.
4. Gilbert DN, Dworkin RJ, Raber SR, et al: Outpatient parenteral antimicrobial-drug therapy. N Engl J Med 1997;337:829-39.
5. Scarborough M, Li HK, Rombach I, et al: Oral versus intravenous antibiotics for bone and joint infections: the OVIVA non-inferiority RCT. Health Technol Assess 2019;23(38):1-92.
6. Obremskey WT, Schmidt AH, O’Toole RV, et al: A prospective randomized trial to assess oral versus intravenous antibiotics for the treatment of postoperative wound infection after extremity fractures (POvIV Study). J Orthop Trauma 2017;31 Suppl 1:S32-8.