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Randomized Controlled Trial
. 2025 Mar 1;160(3):276-284.
doi: 10.1001/jamasurg.2024.6439.

Oral vs Intravenous Antibiotics for Fracture-Related Infections: The POvIV Randomized Clinical Trial

Major Extremity Trauma Research Consortium (METRC); William T Obremskey  1 , Robert V O'Toole  2 , Saam Morshed  3 , Paul Tornetta 3rd  4 , Clinton K Murray  5 , Clifford B Jones  6   7 , Daniel O Scharfstein  8 , Tara J Taylor  8 , Anthony R Carlini  8 , Jennifer M DeSanto  8 , Renan C Castillo  8 , Michael J Bosse  9 , Madhav A Karunakar  9 , Rachel B Seymour  9 , Stephen H Sims  9 , David A Weinrib  9 , Christine Churchill  9 , Eben A Carroll  10 , Holly T Pilson  10 , James Brett Goodman  10 , Martha B Holden  10 , Anna N Miller  11 , Debra L Sietsema  6 , Philip F Stahel  12 , Hassan Mir  13 , Andrew H Schmidt  14 , Jerald R Westberg  14 , Brian Mullis  15 , Karl D Shively  15 , Robert A Hymes  16 , Sanjit R Konda  17 , Heather A Vallier  18 , Mary Alice Breslin  18 , Christopher S Smith  19 , Colin V Crickard  19 , J Spence Reid  20 , Mitch Baker  2 , W Andrew Eglseder  2 , Christopher LeBrun  2 , Theodore Manson  2 , Daniel C Mascarenhas  2 , Jason Nascone  2 , Andrew N Pollak  2 , Michael G Schloss  2 , Marcus F Sciadini  2 , Yasmin Degani  2 , Theodore Miclau  3 , David B Weiss  21 , Seth R Yarboro  21 , Eric D McVey  21 , Reza Firoozabadi  22 , Julie Agel  22 , Eduardo J Burgos  1 , Vamshi Gajari  1 , Andres Rodriguez-Buitrago  1 , Rajesh R Tummuru  1 , Karen M Trochez  1
Affiliations
Randomized Controlled Trial

Oral vs Intravenous Antibiotics for Fracture-Related Infections: The POvIV Randomized Clinical Trial

Major Extremity Trauma Research Consortium (METRC) et al. JAMA Surg. .

Erratum in

  • Error in Byline.
    [No authors listed] [No authors listed] JAMA Surg. 2025 Jul 1;160(7):826. doi: 10.1001/jamasurg.2025.1626. JAMA Surg. 2025. PMID: 40397463 Free PMC article. No abstract available.

Abstract

Importance: Fracture-related infection (FRI) is a serious complication following fracture fixation surgery. Current treatment of FRIs entails debridement and 6 weeks of intravenous (IV) antibiotics. Lab data and retrospective clinical studies support use of oral antibiotics, which are less expensive and may have fewer complications than IV antibiotics.

Objective: To evaluate the effectiveness of treatment of FRI with oral vs IV antibiotics.

Design, setting, and participants: The POvIV multicenter, prospective randomized clinical trial was conducted across 24 trauma centers in the US among patients aged 18 to 84 years who had fracture repair or arthrodesis with fixation with implants and developed an FRI without radiographic evidence of osteomyelitis. Patients were enrolled between March 2013 and September 2018 and followed up for 12 months after hospitalization for treatment of their FRI.

Intervention: Oral vs IV antibiotics following FRI.

Main outcomes and measures: The primary outcome was number of surgical interventions, and the primary hypothesis was noninferiority of oral vs IV antibiotics with respect to the number of study injury-related surgical interventions by 1 year. Unadjusted modified intent-to-treat (mITT) and adjusted per-protocol (PP) analyses were prespecified. A post hoc adjusted mITT analysis was conducted to resolve discrepancies between the results of the prespecified mITT and PP analyses. Recurrence of a deep surgical site infection was a key secondary outcome.

Results: Among 233 total patients, mean (SD) age was 46.0 (13.9) years, and 53 patients were female (22.7%). The mean number of surgical interventions within 1 year was 1.3 and 1.1 for the oral and IV groups, respectively. The upper bound of the 95% confidence interval of the mean difference with unadjusted mITT analysis was 0.59, which was lower than the prespecified noninferiority margin of 0.67, indicating noninferiority of oral to IV antibiotics. Adjusted PP analysis did not support noninferiority of the number of reoperations. A post hoc adjusted mITT analysis also showed noninferiority. The treatment effects estimates for the key secondary outcome of reinfection showed a similar pattern as those for the primary outcome.

Conclusions and relevance: In this prospective randomized clinical trial, oral antibiotic treatment was noninferior to IV treatment with respect to the primary outcome of number of surgical interventions based on mITT analysis. However, there is some uncertainty in these findings based on preplanned and post hoc secondary analyses. A similar pattern of treatment effect estimates was observed for the secondary outcome of recurrence of infection.

Trial registration: ClinicalTrials.gov Identifier: NCT01714596.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Obremskey reported grants from the US Department of Defense (DOD) during the conduct of the study. Dr O’Toole reported grants from DOD during the conduct of the study; consultant fees from Stryker; holding stock options in Imagen; and royalties from Lincotek outside the submitted work. Drs Scharfstein, Taylor, Carlini, and Karunakar reported grants from DOD during the conduct of the study. Dr Carroll reported grants from DOD during the conduct of the study; personal fees and grants from DePuy Synthes; and personal fees from Globus outside the submitted work. Dr Pilson reported serving as a paid presenter for DePuy Synthes outside the submitted work. Dr Sietsema, Schmidt, Konda, and Vallier reported grants from DOD during the conduct of the study. Dr Breslin reported grants from the Major Extremity Trauma Research Consortium (METRC) during the conduct of the study. Dr Eglseder reported grants from DOD both during the conduct of the study and outside the submitted work. Dr Manson reported consultant fees from Stryker and Globus outside the submitted work. Dr Nascone reported consulting fees from DePuy Synthes; holding stock options in Imagen; and royalties from OsteoCentric Technologies outside the submitted work. Dr Pollak reported grants from DOD during the conduct of the study and royalties from Zimmer Biomet and Globus outside the submitted work. Dr Schloss reported grants from DOD during the conduct of the study. Dr Sciadini reported grants from METRC during the conduct of the study. Dr Miclau reported grants from DOD during the conduct of the study. Dr Weiss reported grants from Johns Hopkins University for serving as the METRC coordinating center during the conduct of the study. Dr McVey reported grants from DOD during the conduct of the study. No other disclosures were reported.

Comment on

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