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.

Background The optimal duration and choice of antibiotic for fracture-related infection (FRI) is not well defined. This study aimed to determine whether antibiotic duration (≤6 vs >6 weeks) is associated with infection- and surgery-free survival. The secondary aim was to ascertain risk factors associated with surgery- and infection-free survival. Methods We performed a multicenter retrospective study of patients diagnosed with FRI between 2013 and 2022. The association between antibiotic duration and surgery- and infection-free survival was assessed by Cox proportional hazard models. Models were weighted by the inverse of the propensity score, calculated with a priori variables of hardware removal; infection due to Staphylococcus aureus, Staphylococcus lugdunensis, Pseudomonas or Candida species; and flap coverage. Multivariable Cox proportional hazard models were run with additional covariates including initial pathogen, need for flap, and hardware removal. Results Of 96 patients, 54 (56.3%) received ≤6 weeks of antibiotics and 42 (43.7%) received >6 weeks. There was no association between longer antibiotic duration and surgery-free survival (hazard ratio [HR], 0.95; 95% CI, .65–1.38; P = .78) or infection-free survival (HR, 0.77; 95% CI, .30–1.96; P = .58). Negative culture was associated with increased hazard of reoperation or death (HR, 3.52; 95% CI, 1.99–6.20; P < .001) and reinfection or death (HR, 3.71; 95% CI, 1.24–11.09; P < .001). Need for flap coverage had an increased hazard of reoperation or death (HR, 3.24; 95% CI, 1.61–6.54; P = .001). Conclusions The ideal duration of antibiotics to treat FRI is unclear. In this multicenter study, there was no association between antibiotic treatment duration and surgery- or infection-free survival.

Background: Studies evaluating surgical-site infection have had conflicting results with respect to the use of alcohol solutions containing iodine povacrylex or chlorhexidine gluconate as skin antisepsis before surgery to repair a fractured limb (i.e., an extremity fracture). Methods: In a cluster-randomized, crossover trial at 25 hospitals in the United States and Canada, we randomly assigned hospitals to use a solution of 0.7% iodine povacrylex in 74% isopropyl alcohol (iodine group) or 2% chlorhexidine gluconate in 70% isopropyl alcohol (chlorhexidine group) as preoperative antisepsis for surgical procedures to repair extremity fractures. Every 2 months, the hospitals alternated interventions. Separate populations of patients with either open or closed fractures were enrolled and included in the analysis. The primary outcome was surgical-site infection, which included superficial incisional infection within 30 days or deep incisional or organ-space infection within 90 days. The secondary outcome was unplanned reoperation for fracture-healing complications. Results: A total of 6785 patients with a closed fracture and 1700 patients with an open fracture were included in the trial. In the closed-fracture population, surgical-site infection occurred in 77 patients (2.4%) in the iodine group and in 108 patients (3.3%) in the chlorhexidine group (odds ratio, 0.74; 95% confidence interval [CI], 0.55 to 1.00; P = 0.049). In the open-fracture population, surgical-site infection occurred in 54 patients (6.5%) in the iodine group and in 60 patients (7.3%) in the chlorhexidine group (odd ratio, 0.86; 95% CI, 0.58 to 1.27; P = 0.45). The frequencies of unplanned reoperation, 1-year outcomes, and serious adverse events were similar in the two groups. Conclusions: Among patients with closed extremity fractures, skin antisepsis with iodine povacrylex in alcohol resulted in fewer surgical-site infections than antisepsis with chlorhexidine gluconate in alcohol. In patients with open fractures, the results were similar in the two groups. (Funded by the Patient-Centered Outcomes Research Institute and the Canadian Institutes of Health Research; PREPARE ClinicalTrials.gov number, NCT03523962.).

This international, multi-center study investigated the effect of individual components of surgery on the clinical outcomes of patients treated for fracture-related infection (FRI). All patients with surgically treated FRIs, confirmed by the FRI consensus definition, were included. Data were collected on demographics, time from injury to FRI surgery, soft tissue reconstruction, stabilization and systemic and local anti-microbial therapy. Patients were followed up for a minimum of one year. In total, 433 patients were treated with a mean age of 49.7 years (17–84). The mean follow-up time was 26 months (range 12–72). The eradication of infection was successful in 86.4% of all cases and 86.0% of unhealed infected fractures were healed at the final review. In total, 3.3% required amputation. The outcome was not dependent on age, BMI, the presence of metalwork or time from injury (recurrence rate 16.5% in FRI treated at 1–10 weeks after injury; 13.1% at 11–52 weeks; 12.1% at >52 weeks: p = 0.52). The debridement and retention of a stable implant (DAIR) had a failure rate of 21.4%; implant exchange to a new internal fixation had a failure rate of 12.5%; and conversion to external fixation had a failure rate of 10.3% (adjusted hazard ratio (aHR) DAIR vs. Ext Fix 2.377; 95% C.I. 0.96–5.731). Tibial FRI treated with a free flap was successful in 92.1% of cases and in 80.4% of cases without a free flap (HR 0.38; 95% C.I. 0.14–1.0), while the use of NPWT was associated with higher recurrence rates (HR 3.473; 95% C.I. 1.852–6.512). The implantation of local antibiotics reduced the recurrence from 18.7% to 10.0% (HR 0.48; 95% C.I. 0.29–0.81). The successful treatment of FRI was multi-factorial. These data suggested that treatment decisions should not be based on time from injury alone, as other factors also affected the outcome. Further work to determine the best indications for DAIR, free flap reconstruction and local antibiotics is warranted.

Importance: Despite the widespread use of systemic antibiotics to prevent infections in surgically treated patients with fracture, high rates of surgical site infection persist. Objective: To examine the effect of intrawound vancomycin powder in reducing deep surgical site infections. Design, setting, and participants: This open-label randomized clinical trial enrolled adult patients with an operatively treated tibial plateau or pilon fracture who met the criteria for a high risk of infection from January 1, 2015, through June 30, 2017, with 12 months of follow-up (final follow-up assessments completed in April 2018) at 36 US trauma centers. Interventions: A standard infection prevention protocol with (n = 481) or without (n = 499) 1000 mg of intrawound vancomycin powder. Main outcomes and measures: The primary outcome was a deep surgical site infection within 182 days of definitive fracture fixation. A post hoc comparison assessed the treatment effect on gram-positive and gram-negative-only infections. Other secondary outcomes included superficial surgical site infection, nonunion, and wound dehiscence. Results: The analysis included 980 patients (mean [SD] age, 45.7 [13.7] years; 617 [63.0%] male) with 91% of the expected person-time of follow-up for the primary outcome. Within 182 days, deep surgical site infection was observed in 29 of 481 patients in the treatment group and 46 of 499 patients in the control group. The time-to-event estimated probability of deep infection by 182 days was 6.4% in the treatment group and 9.8% in the control group (risk difference, -3.4%; 95% CI, -6.9% to 0.1%; P = .06). A post hoc analysis of the effect of treatment on gram-positive (risk difference, -3.7%; 95% CI, -6.7% to -0.8%; P = .02) and gram-negative-only (risk difference, 0.3%; 95% CI, -1.6% to 2.1%; P = .78) infections found that the effect of vancomycin powder was a result of its reduction in gram-positive infections. Conclusions and relevance: Among patients with operatively treated tibial articular fractures at a high risk of infection, intrawound vancomycin powder at the time of definitive fracture fixation reduced the risk of a gram-positive deep surgical site infection, consistent with the activity of vancomycin.

Background: Open fractures are one of the leading causes of disability worldwide. The threshold time to debridement that reduces the infection rate is unclear. Methods: We searched all available databases to identify observational studies and randomized trials related to open fracture care. We then conducted an extensive meta-analysis of the observational studies, using raw and adjusted estimates, to determine if there was an association between the timing of initial debridement and infection. Results: We identified 84 studies (18,239 patients) for the primary analysis. In unadjusted analyses comparing various “late” time thresholds for debridement versus “early” thresholds, there was an association between timing of debridement and surgical site infection (odds ratio [OR] = 1.29, 95% confidence interval [CI] = 1.11 to 1.49, p < 0.001, I2 = 30%, 84 studies, n = 18,239). For debridement performed between 12 and 24 hours versus earlier than 12 hours, the OR was higher in tibial fractures (OR = 1.37, 95% CI = 1.00 to 1.87, p = 0.05, I2= 19%, 12 studies, n = 2,065), and even more so in Gustilo type-IIIB tibial fractures (OR = 1.46, 95% CI = 1.13 to 1.89, p = 0.004, I2 = 23%, 12 studies, n = 1,255). An analysis of Gustilo type-III fractures showed a progressive increase in the risk of infection with time. Critical time thresholds included 12 hours (OR = 1.51, 95% CI = 1.28 to 1.78, p < 0.001, I2 = 0%, 16 studies, n = 3,502) and 24 hours (OR = 2.17, 95% CI = 1.73 to 2.72, p < 0.001, I2 = 0%, 29 studies, n = 5,214). Conclusions: High-grade open fractures demonstrated an increased risk of infection with progressive delay to debridement.

Fracture-related infection (FRI) remains a challenging complication that creates a heavy burden for orthopaedic trauma patients, their families and treating physicians, as well as for healthcare systems. Standardization of the diagnosis of FRI has been poor, which made the undertaking and comparison of studies difficult. Recently, a consensus definition based on diagnostic criteria for FRI was published. As a well-established diagnosis is the first step in the treatment process of FRI, such a definition should not only improve the quality of published reports but also daily clinical practice. The FRI consensus group recently developed guidelines to standardize treatment pathways and outcome measures. At the center of these recommendations was the implementation of a multidisciplinary team (MDT) approach. If such a team is not available, it is recommended to refer complex cases to specialized centers where a MDT is available and physicians are experienced with the treatment of FRI. This should lead to appropriate use of antimicrobials and standardization of surgical strategies. Furthermore, an MDT could play an important role in host optimization. Overall two main surgical concepts are considered, based on the fact that fracture fixation devices primarily target fracture consolidation and can be removed after healing, in contrast to periprosthetic joint infection were the implant is permanent. The first concept consists of implant retention and the second consists of implant removal (healed fracture) or implant exchange (unhealed fracture). In both cases, deep tissue sampling for microbiological examination is mandatory. Key aspects of the surgical management of FRI are a thorough debridement, irrigation with normal saline, fracture stability, dead space management and adequate soft tissue coverage. The use of local antimicrobials needs to be strongly considered. In case of FRI, empiric broad-spectrum antibiotic therapy should be started after tissue sampling. Thereafter, this needs to be adapted according to culture results as soon as possible. Finally, a minimum follow-up of 12 months after cessation of therapy is recommended. Standardized patient outcome measures purely focusing on FRI are currently not available but the patient-reported outcomes measurement information system (PROMIS) seems to be the preferred tool to assess the patients’ short and long-term outcome. This review summarizes the current general principles which should be considered during the whole treatment process of patients with FRI based on recommendations from the FRI Consensus Group.

Fracture-related infection (FRI) is a common and serious complication in trauma surgery. Accurately estimating the impact of this complication has been hampered by the lack of a clear definition. The absence of a working definition of FRI renders existing studies difficult to evaluate or compare. In order to address this issue, an expert group comprised of a number of scientific and medical organizations has been convened, with the support of the AO Foundation, in order to develop a consensus definition. The process that led to this proposed definition started with a systematic literature review, which revealed that the majority of randomized controlled trials in fracture care do not use a standardized definition of FRI. In response to this conclusion, an international survey on the need for and key components of a definition of FRI was distributed amongst all registered AOTrauma users. Approximately 90% of the more than 2000 surgeons who responded suggested that a definition of FRI is required. As a final step, a consensus meeting was held with an expert panel. The outcome of this process led to a consensus definition of FRI. Two levels of certainty around diagnostic features were defined. Criteria could be confirmatory (infection definitely present) or suggestive. Four confirmatory criteria were defined: Fistula, sinus or wound breakdown; Purulent drainage from the wound or presence of pus during surgery; Phenotypically indistinguishable pathogens identified by culture from at least two separate deep tissue/implant specimens; Presence of microorganisms in deep tissue taken during an operative intervention, as confirmed by histopathological examination. Furthermore, a list of suggestive criteria was defined. These require further investigations in order to look for confirmatory criteria. In the current paper, an overview is provided of the proposed definition and a rationale for each component and decision. The intention of establishing this definition of FRI was to offer clinicians the opportunity to standardize clinical reports and improve the quality of published literature. It is important to note that the proposed definition was not designed to guide treatment of FRI and should be validated by prospective data collection in the future.