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. 2025 Nov 19;107(22):2541-2553.
doi: 10.2106/JBJS.24.01055. Epub 2025 Nov 19.

Infection and Nonunion Rates in Open Fractures: Description of 6,042 Fractures from the FLOW and PREP-IT Trials

Roman M Natoli  1 , Lucas S Marchand  2 , Sofia Bzovsky  3 , Jennifer E Hagen  4 , Mark J Gage  5 , Christina A Stennett  5 , Nathan N O'Hara  5 , Kyle J Jeray  6 , Brad Petrisor  3 , Sheila Sprague  3   7 , Gerard P Slobogean  5 ; FLOW Investigators; PREP-IT Investigators; FLOW Investigators and the PREP-IT Investigators
Collaborators, Affiliations

Infection and Nonunion Rates in Open Fractures: Description of 6,042 Fractures from the FLOW and PREP-IT Trials

Roman M Natoli et al. J Bone Joint Surg Am. .

Abstract

Background: Infection and nonunion are common sequelae of open fractures. Studies have shown infection and nonunion rates ranging from 2% to 52% and 12% to 17%, respectively. The present article describes the rates of surgical site infection (SSI) and delayed union/nonunion following open fractures in a large contemporary series of patients from prospective clinical trials with adjudicated outcomes.

Methods: A descriptive analysis was performed with use of patient data from the FLOW, Aqueous-PREP, and PREPARE-Open studies. These studies, published within the past 10 years, included multiple international trauma centers and shared definitions for SSI and delayed union/nonunion. SSI and delayed union/nonunion rates were stratified by the OTA/AO fracture and Gustilo-Anderson open fracture classification systems. Kaplan-Meier estimators were utilized to obtain point estimates, and the log-log transformation approach was utilized to calculate 95% confidence intervals (CIs) for outcome rates.

Results: A total of 6,042 open fractures were included. The cumulative SSI rates at 12 months for Gustilo-Anderson Types 1, 2, 3A, 3B, and 3C were 5.1%, 9.7%, 13.8%, 28.9%, and 26.2%, respectively. The cumulative rates of delayed union/nonunion at 12 months for Gustilo-Anderson Types 1, 2, 3A, 3B, and 3C were 3.0%, 5.2%, 8.0%, 14.0%, and 17.0%, respectively. Utilizing the OTA/AO fracture classification to increase the point estimate granularity, the estimated 12-month SSI and delayed union/nonunion rates in 156 Gustilo-Anderson type 3B open tibial shaft fractures (OTA/AO 42) were 34.7% (95% CI, 26.7% to 41.9%) and 18.4% (95% CI, 12.0% to 24.4%), respectively. A companion website with SSI and delayed union/nonunion rates was developed to supplement this article.

Conclusions: Open fractures are a substantial problem with complications that include infection and nonunion. The present data are useful for prognosis, research study design, and informing public awareness and policy. These results show that, despite current treatment approaches, the rates of SSI and delayed union/nonunion following treatment of open fractures remain high at 1 year and are not substantially improved from historical rates spanning several decades. Although open fracture sequelae remain a burden for patients, orthopaedic surgeons, and health-care systems, there may be opportunities for improvement in outcomes.

Level of evidence: Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence.

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Conflict of interest statement

Disclosure: The Aqueous-PREP study was funded by the US Department of Defense (W81XWH-17-1-070), a Canadian Institutes of Health Research Foundation Grant, McMaster University Surgical Associates, and the PSI (Physicians’ Services Incorporated) Foundation. The PREPARE trial was funded by the Patient-Centered Outcomes Research Institute and the Canadian Institutes of Health Research. Research reported in this publication was also partially supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number 2K24AR076445. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The FLOW trial was supported by research grants from the Canadian Institutes of Health Research (MCT-93173), United States Army Institute of Surgical Research, Orthopaedic Trauma Research Program (OTRP) and Peer Reviewed Orthopaedic Research Program (PRORP), and Association Internationale pour l’Ostéosynthèse Dynamique (AIOD). Stryker provided Surgilav irrigators for the trial for clinical sites in Asia. Zimmer provided Pulsavac irrigators at discounted rates to selected clinical sites in North America. Triad Medical donated the initial supply of castile soap for the study. The FLOW trial was also supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Orthopaedic Trauma Research Program under Award W81XWH-08-1-0473 and the Peer Reviewed Orthopaedic Research Program under Award W81XWH-12-1-0530. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/I840).

Figures

Fig. 1
Fig. 1
Heat maps of 12-month infection rates (per the color scale at left) and nonunion rates (per the color scale at right) for each Gustilo-Anderson open fracture type. Each anatomical location is labeled according to the OTA/AO fracture classification. Data are based on Tables II through V, and combinations of OTA/AO fracture location and Gustilo-Anderson severity with <10 fractures are omitted.
Fig. 2
Fig. 2
Histogram of event rates by time interval for SSI (Fig. 2-A) and delayed union/nonunion (Fig. 2-B). SSIs were predominantly identified within the first 3 months, whereas delayed unions/nonunions were predominantly identified between 6 and 12 months. For each Gustilo-Anderson classification, the bars sum to the cumulative event rates provided in Appendix Tables S5A and S5B for SSI and delayed union/nonunion, respectively.
See this image and copyright information in PMC

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