Oral Antibiotics Noninferior to IV Treatment for Fracture-Related Infections: JAMA

The authors revealed that oral antibiotic treatment was noninferior to intravenous treatment concerning the primary outcome, the number of surgical interventions, as determined by the mITT analysis. However, the researchers noted some uncertainty in these findings based on the results of preplanned and post hoc secondary analyses. A similar trend in treatment effect estimates was observed for the secondary outcome, which evaluated the recurrence of infection. The findings were published online in JAMA Surgery.

Fracture-related infection is a significant complication following fracture fixation surgery, often requiring debridement and a six-week course of IV antibiotics as the standard treatment. While IV antibiotics have been the traditional approach, laboratory data, and retrospective clinical studies suggest that oral antibiotics could be an effective alternative, offering advantages such as lower costs and potentially fewer complications.

Against this backdrop, William T. Obremskey, MD, MPH, MMHC, Vanderbilt University Medical Center, Nashville, TN, and colleagues from the Major Extremity Trauma Research Consortium (METRC), aimed to evaluate the effectiveness of oral antibiotics compared to IV antibiotics in the treatment of FRIs, providing evidence to inform future clinical decision-making.

For this purpose, the researchers conducted the POvIV multicenter, prospective randomized clinical trial across 24 trauma centers in the US, enrolling patients aged 18 to 84 years with fracture repair or arthrodesis involving implants who developed fracture-related infections (FRIs) without radiographic evidence of osteomyelitis. Patients were followed for 12 months after hospitalization between March 2013 and September 2018.

The trial compared oral and intravenous (IV) antibiotics. The primary outcome was the number of study injury-related surgical interventions within a year. Secondary outcomes included the recurrence of deep surgical site infections, which were analyzed using preplanned and post hoc methods to ensure reliability.

The following were the key findings of the study:

• The study included 233 patients with a mean age of 46.0 years, and 22.7% of patients were female.
• The mean number of surgical interventions within one year was 1.3 for the oral group and 1.1 for the IV group.
• The upper bound of the 95% confidence interval for the mean difference in the unadjusted mITT analysis was 0.59, which was below the prespecified noninferiority margin of 0.67, suggesting noninferiority of oral to IV antibiotics.
• The adjusted PP analysis did not support the noninferiority of the number of reoperations.
• A post hoc adjusted mITT analysis indicated noninferiority.
• The treatment effect estimates for reinfection, a key secondary outcome, followed a similar pattern to the primary outcome.

The POvIV randomized clinical trial demonstrates that oral antibiotics are noninferior to IV antibiotics for the primary outcome of surgical interventions based on mITT analyses. However, oral antibiotics did not show noninferiority in the secondary PP analysis. While reinfection rates were similar in the unadjusted mITT analysis, adjusted mITT and PP analyses revealed greater differences.

"These findings can assist clinicians and patients in making informed decisions about antibiotic care for FRIs," the researchers concluded.

Reference:

Major Extremity Trauma Research Consortium (METRC). Oral vs Intravenous Antibiotics for Fracture-Related Infections: The POvIV Randomized Clinical Trial. JAMA Surg. Published online January 22, 2025. doi:10.1001/jamasurg.2024.6439