Patients with an orthopedic infection treated with debridement and an implanted antibiotic fared as well over 12 months whether they received a short (≤7 days) or standard duration (≥4 weeks) course of systemic antibiotic, according to the findings of a multicenter trial.1
"This trial challenges the standard of care for orthopedic infection, which usually includes at least 4 weeks of postoperative systemic antibiotic treatment," declare Martin McNally, MD, Bone infection Unit, Nuffield Orthopaedic Centre, Oxford University Hospitals, Oxford, United Kingdom, and colleagues.
The investigators conducted the multi-center, open-label, noninferiority trial with 475 patients randomized on 1:1 basis to receive a short or standard duration of antibiotic treatment following debridement and implanted antibiotic for an orthopedic infection.457 participants remained eligible after vetting for trial protocol violations; with an additional 11 excluded for surgical site cultures resistant to the local antibiotic, and 3 in the long-duration group and 8 in the short-duration group lost to follow-up before 12 months.
The localized and systemic antibiotics were chosen by infectious disease specialists at the trial site.The implanted devices—either an absorbable or a polymethylmethacrylate (PMMA)-based carrier—eluted high antibiotic concentration at the infection site for at least 4 weeks.
The primary outcome was treatment failure within 12 months of surgery defined by the presence of at least one of the following: sinus tract or purulence at surgical site, microbiologic or histologic identification of infection at reoperation, newly elevated biomarkers in synovial fluid on aspiration or reoperation, or death from infection at the index surgical site. Secondary outcomes included potential antibiotic side effects and serious adverse effects.
McNally and colleagues reported definite treatment failure occurred within 1 year in 14.1% of patients in the long-duration group and in 11.1% in the short duration group, meeting the preset 10% difference criteria for non-inferiority.Overall survival at 12 months was 96.3% in the long-duration group and 97.9% in the short duration group.
What You Need to Know
In a 475-patient multicenter trial, a short (≤7 days) course of systemic antibiotics after debridement and local antibiotic implant was noninferior to a standard course (≥4 weeks) for preventing treatment failure in orthopedic infections at 12 months.
Treatment failure occurred in 14.1% of the long-duration group versus 11.1% of the short-duration group, meeting noninferiority criteria, while 12-month survival was similar between groups (96.3% vs. 97.9%).
The short-duration regimen was associated with notably fewer antibiotic-related adverse events (17.2% vs. 45.2% at 6 weeks) and a shorter average hospital stay, suggesting shorter systemic courses may be a safer option when local antibiotics are also used.
Adverse events related to the antibiotic treatment at 6 weeks, however, had occurred in 45.2% of those in the long-duration group, compared to 17.2% with short antibiotic regimens.The adverse events included 2 patients in the long-duration group with new onset C difficile infection; both severe and occurring within 6 weeks of surgery
Adverse symptoms were also reported between 3 and 6 months by 20.4% of those in the long-duration group and 8.5% with the short regimen. Other secondary outcome measures were comparable between groups, including the mean duration hospital stay of 14.8 days in the long-duration group and 11.9 days with the short regimen.
McNally and colleagues cite studies that associate the addition of local, implanted antibiotic treatment to systemic regimens with lower risk of treatment failure; and others that support the primary use of local antibiotic therapy for orthopedic infections.
"However, although data from the current trial support the utility of local antibiotics in reducing the need for prolonged systemic antibiotics, a substantial amount of high-quality data is needed before local therapy is adopted as the primary approach in clinical practice," McNally and colleagues indicate.
Reference
1. McNally M, Dudareva M, Kümin M, et al. Short or long antibiotic regimens in orthopedics. N Engl J Med. 2026, Online September 16; doi:10.1056/NEJMoa2506756
