Impact of infectious disease specialist consultations on antibiotic treatment and outcomes of fracture-related infections 

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This study aimed to investigate the effects of ID consultations on antibiotic treatment and FRI outcomes. Methods We conducted a retrospective chart review of data from adult patients with microbiologically diagnosed FRIs at a tertiary care hospital. Results In total, 123 patients with FRIs were included in the study, with a median follow-up period of 31 months. Sixty-five patients (52.8%) received continuous ID consultations until the completion of their treatment, whereas 58 patients (47.2%) either did not receive any ID consultations or had their consultations terminated prematurely. The patients who received continuous ID consultations were more likely to receive pathogen-directed oral antibiotics (76.9% vs. 36.2%; P < 0.001), biofilm-active antibiotics (52.3% vs. 8.6%; P < 0.001), and prolonged antibiotic treatment (median, 50 vs. 26 days; P < 0.001) than those who did not receive such consultations. The multivariate analysis results indicated that Gustilo–Anderson grade 3 open fractures (adjusted odds ratio [aOR], 3.82; P = 0.002), implant retention (aOR, 3.01; P = 0.02), and absence or early termination of ID consultations (aOR, 3.17; P = 0.009) were independent predictors of treatment failure. Recurrence was less frequent in the patients who received biofilm-active agents than in those who did not (10.3% vs. 35.7%; P = 0.007). Conclusion In patients with FRI, appropriate ID consultations were associated with frequent use of biofilm-active antibiotics and improved outcomes. Health sciences/Diseases/Infectious diseases/Bacterial infection Health sciences/Anatomy/Musculoskeletal system/Bone biofilm-active agent duration of antibiotic therapy fixation fracture-related infections implant failure Figures Figure 1 Figure 2 Introduction Fracture-related infection (FRI) is a critical complication of trauma surgery that significantly affects patient outcomes and poses risks such as permanent functional loss or amputation. The prevalence of FRI is considerable and estimated at approximately 1–2% in closed fractures with internal fixation and up to 30% in open fractures [ 1 ]. These rates are expected to increase with the growing number of fracture-related surgeries, particularly in the older adult population [ 2 ]. The management of FRIs is inherently complex owing to several factors. FRIs develop from infections in orthopedic devices inserted after trauma and are often accompanied by soft tissue and vascular damage. This damage can impair wound healing and the local blood supply, hindering the delivery of antibiotics and immune cells to the site of infection. The variability in fracture types and locations further adds to the complexity. Surgical treatment often involves multiple procedures, including debridement (removal of infected and necrotic tissue), stabilization of the fracture, and removal and replacement of hardware. Maintaining fracture stability is crucial, and complete fixative removal in FRIs is feasible only after bone union is achieved. In patients who require orthopedic devices for stabilization, optimal antibiotics should be carefully selected to eradicate biofilm-embedded bacteria on the surface of the orthopedic devices and to prevent recurrence [ 3 – 5 ]. These complexities require collaboration among multiple medical disciplines, including trauma, orthopedics, and vascular surgeons, as well as infectious disease (ID) specialists, microbiologists, and pharmacists [ 4 – 8 ]. ID specialists play a critical role in selecting optimal initial antibiotics based on diagnostic test results and patient conditions. Furthermore, their involvement is essential throughout the treatment period to determine the timing for transitioning from intravenous to suitable oral antibiotics, assess treatment tolerability, and provide alternative therapeutic options when necessary. Multiple studies encompassing a wide range of infections and hospital settings showed that patients who received ID consultations were prescribed more appropriate antibiotics and had better prognoses [ 9 ]. However, limited data exist regarding the role of ID specialists in the management of orthopedic device-related infections. This study aimed to evaluate the impact of ID specialist involvement on antibiotic treatment and outcomes of FRIs. Methods Study design This study was conducted at an 850-bed tertiary care academic center. We retrospectively reviewed the medical charts of all consecutively enrolled adult patients with suspected FRIs between January 2008 and December 2022. The study was approved by the Institutional Review Board of Kyung Hee University Hospital (IRB number: 2023-11-060). Due to the retrospective nature of the study, the Institutional Review Board of Kyung Hee University Hospital waived the need of obtaining informed consent. Inclusion and exclusion criteria Patients with definite FRIs, as defined by the consensus of an international expert group [ 4 ], were included. Briefly, patients were considered to have a definite FRI if they had (i) fistula, sinus, or wound breakdown; (ii) purulent drainage from the wound or pus exudation during surgery; or (iii) phenotypically indistinguishable pathogens identified through cultures of at least two separate deep-tissue specimens [ 4 ]. To ensure clarity of the relationship between antimicrobial selection and treatment outcomes, only microbiologically confirmed cases were assessed in this study. Other reasons for exclusion were incomplete medical records and death before the completion of the antibiotic therapy. FRIs were classified as early (0–2 weeks after implantation), delayed (3–10 weeks), or late (≥ 10 weeks) [ 1 , 4 , 10 , 11 ]. Data collection We retrospectively reviewed the medical records for demographic information, underlying illness/condition, characteristics of fractures and FRIs, medical and surgical treatments, and clinical outcomes. To quantify the overall comorbidity burden, we calculated the Charlson Comorbidity Index (CCI) scores using codes from the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) [ 12 , 13 ]. Treatment The decision for surgical therapy, including implant retention and use of local antibiotics, was at the discretion of the treating physicians. Retaining the implant requires construct stability that facilitates bone healing, adequate surgical debridement, and soft tissue coverage [ 5 , 11 ]. The fixation implant was removed if the bone had healed or exchanged if the bone required further stabilization [ 5 , 6 , 11 ]. Local elution of antibiotics was achieved using antibiotic-impregnated polymethyl methacrylate (PMMA) cement beads and spacers [ 14 , 15 ]. Biofilm-active antibiotic therapy was defined as the administration of a rifampin-based combination for staphylococci or fluoroquinolone for gram-negative bacteria. The intravenous companion drugs for rifampin include nafcillin, cefazolin, vancomycin, and teicoplanin. The oral companion drugs for rifampin include fluoroquinolones, trimethoprim–sulfamethoxazole, fusidic acid, clindamycin, and linezolid [ 4 , 16 ]. The duration of antibiotic therapy was determined based solely on the antimicrobial agents that were appropriate for the isolated organisms and their susceptibility profiles. ID consultation The decision to conduct ID consultations was made by the treating physicians. We divided the patients into two groups to assess the appropriateness of these consultations. The appropriate ID consultation group consisted of patients who received continuous ID consultations throughout their treatment, until the completion of antimicrobial therapy. The inappropriate ID consultation group included patients who either did not receive any ID consultations or whose consultations were prematurely discontinued before the completion of antibiotic therapy. Outcomes Treatment failure was defined as primary failure, infection recurrence, and/or amputation after surgery. Primary failure was defined as new surgical debridement after the initial definite surgery for infection or skin coverage before the end of antibiotic treatment because of signs of uncontrolled infection. Recurrence was defined as unplanned surgery after the completion of antibiotic therapy because of infection recurrence based on the aforementioned definite criteria for FRIs [ 11 ]. Detection of the same pathogen(s) as in the first episode, as well as a new or no pathogen, was interpreted as recurrence, unless conclusive evidence favored new hematogenous seeding after bloodstream infection. Statistical analyses All analyses were performed using the R statistical software (version 4.3.3; R Foundation for Statistical Computing, Vienna, Austria). Categorical variables were compared using the chi-square test or Fisher’s exact test, and continuous variables were compared using the Mann–Whitney U test. Univariate and multivariate analyses of the parameters predictive of treatment failure and recurrence were performed using logistic regression. All variables with a significant result in the univariate analysis were considered in the multivariate logistic regression model. Antibiotic selection and duration of use were included in the multivariate model for recurrence but not in the model for treatment failure, as primary failures occurred before the completion of antibiotic therapy. The treatment failure- and recurrence-free survival rates were estimated using the Kaplan–Meier method, and the survival curves of the two groups were compared using the log-rank test. All tests for statistical significance were two-tailed, and P -values ≤ 0.05 were considered to indicate statistical significance. Results During the study period, FRI was suspected in 189 patients. Among these, 151 met the predefined criteria for definite FRI. Of the 151 definite FRIs, 28 were excluded for the following reasons: no microbiological confirmation ( n = 21), loss to follow-up within one year ( n = 4), incomplete medical records ( n = 2), and nontuberculous mycobacterial infection (n = 1). Ultimately, data from 123 cases of definite FRIs were included in the final analysis, of which 11 cases (8.9%) were of early FRI, 21 (17.1%) of delayed FRI, and 91 (74.0%) of late FRI (Fig. 1 ). All except one of the 18 patients in the implant exchange cohort underwent one-stage exchange. Consequently, we classified the exchange group as part of the implant retention group in the outcome analysis. Patients’ characteristics The clinical characteristics of the 123 patients with FRIs are presented in Table 1 . The median age of the participants was 50 years (interquartile range [IQR], 33–66 years) and 95 (77.2%) were male. Forty-one patients (33.3%) had diabetes mellitus and 11 (8.9%) had underlying malignancies. Fifty-three (43.1%) of the 123 patients with infections were managed with implant retention, 18 (14.6%) with implant exchange, and 52 (42.3%) with implant removal (Fig. 1 ). Table 1 Characteristics of the 123 patients with microbiologically diagnosed fracture-related infections Variable Early FRI ( n = 11) Delayed FRI ( n = 21) Late FRI ( n = 91) All cases ( n = 123) Patient characteristics Age, years 50 (32–65) 45 (23–63) 50 (34–66) 50 (33–66) Male sex 6 (54.5) 16 (76.2) 73 (80.2) 95 (77.2) Body mass index ≥ 25 kg/m 2 7 (63.6) 6 (28.6) 33 (36.3) 46 (37.4) Current smoker 5 (45.5) 7 (33.3) 23 (25.3) 35 (28.5) Harmful alcohol consumption a 5 (45.5) 4 (19.0) 6 (6.6) 15 (12.2) Diabetes mellitus 3 (27.3) 7 (33.3) 31 (34.1) 41 (33.3) Malignancy 0 1 (4.8) 10 (11.0) 11 (8.9) Cerebrovascular accident 2 (18.2) 0 6 (6.6) 8 (6.5) Charlson Comorbidity Index score 0 7 (63.6) 12 (57.1) 53 (58.2) 72 (58.5) 1–3 3 (27.3) 7 (33.4) 25 (27.5) 35 (28.5) ≥ 4 1 (9.1) 2 (9.5) 13 (14.3) 16 (13.0) Characteristics of fracture Injury severity of fracture Closed fracture 5 (45.5) 13 (61.9) 48 (52.7) 66 (53.7) Open fracture, GA grade 1 1 (9.1) 0 0 1 (0.8) Open fracture, GA grade 2 1 (9.1) 2 (9.5) 13 (14.3) 16 (13.0) Open fracture, GA grade 3 4 (36.4) 6 (28.6) 30 (33.0) 40 (32.5) Comminuted fracture 10 (90.9) 14 (66.7) 41 (45.1) 65 (52.8) Site of fracture Tibia and fibula 5 (45.5) 10 (47.6) 45 (49.5) 60 (48.8) Femur 0 1 (4.8) 27 (29.7) 28 (22.8) Ankle and foot 4 (36.4) 2 (9.5) 10 (11.0) 16 (13.0) Radius and ulna 1 (9.1) 2 (9.5) 7 (7.7) 10 (8.1) Humerus 1 (9.1) 2 (9.5) 1 (1.1) 4 (3.3) Other 0 4 (19.0) 0 4 (3.3) Multiple sites 0 0 1 (1.1) 1 (0.8) Characteristics of infection Fistula or sinus tract 0 1 (4.8) 13 (14.3) 14 (11.4) Purulent discharge 8 (72.7) 7 (33.3) 29 (31.9) 44 (35.8) Pain 6 (54.5) 18 (85.7) 61 (67.0) 85 (69.1) Redness 2 (18.2) 2 (9.5) 15 (16.5) 19 (15.4) Swelling 4 (36.4) 5 (23.8) 24 (26.4) 33 (26.8) Local warmth 0 (0.0) 4 (19.0) 10 (11.0) 14 (11.4) Fever (> 38°C) 2 3 (14.3) 3 (3.3) 8 (6.5) WBC, ×10 9 /mL 5.6 (4.4– 7.7) 8.0 (7.4– 9.7) 7.2 (6.0– 8.8) 7.4 (6.0– 9.0) ESR, mm/h 34 (22–62) 65 (27–86) 39 (24–70) 43 (24–74) CRP, mg/dL 3.9 (0.9– 8.9) 2.1 (0.5– 7.3) 0.9 (0.4– 2.8) 1.1 (0.4– 4.0) Causative pathogens Staphylococcus aureus 1 (9.1) 8 (38.1) 56 (61.5) 65 (52.8) Methicillin-susceptible S. aureus 0 2 (9.5) 20 (22.0) 22 (17.8) Methicillin-resistant S. aureus 1 (9.1) 6 (28.6) 36 (39.5) 43 (35.0) Coagulase-negative staphylococci 3 (27.3) 3 (14.3) 12 (13.2) 17 (14.6) Enterococcus species 0 0 3 (3.3) 3 (2.5) Enterobacteriaceae 4 (36.4) 1 (4.7) 5 (5.5) 10 (8.1) Pseudomonas aeruginosa 1 (9.1) 7 (33.3) 9 (9.9) 17 (13.8) Stenotrophomonas maltophilia 1 (9.1) 0 1 (1.1) 2 (1.6) Other 0 1 (4.8) 3 (3.3) 4 (3.3) Polymicrobial 1 (9.1) 1 (4.8) 2 (2.2) 4 (3.3) Data are presented as numbers (%) or median (interquartile range), unless otherwise indicated. Abbreviations: CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; GA, Gustilo–Anderson; FRI, fracture-related infection; WBC, white blood cells a Defined as consuming more than two standard drinks per day in men and more than one standard drink per day in women The most common site of fracture was the tibia/fibula (48.8%), followed by the femur (22.8%) and ankle/foot (13.0%). Staphylococcus aureus was the most common causative pathogen (52.8%), followed by coagulase-negative staphylococci (14.6%), Pseudomonas aeruginosa (13.8%), and Enterobacteriaceae (8.1%). Implants were initially removed in 27.3% (3/11) of the patients with early FRIs, 42.9% (9/21) with delayed FRIs, and 44.0% (40/91) of patients with late FRIs (Fig. 1 ). Antibiotic treatment The types, routes, and duration of antimicrobial therapy received for FRIs are summarized in Table 2 . The median duration of intravenous antibiotic therapy was 21 days (IQR, 12–34 days). Among the 83 patients with staphylococcal infections, primary parenteral therapy consisted of glycopeptides in 41 (49.4%) and cefazolin in 27 (32.5%). Among the 29 patients with gram-negative bacterial infections, primary parenteral therapy consisted of piperacillin–tazobactam in nine (31.1%) and extended-spectrum cephalosporins in seven (24.1%). Table 2 Antimicrobial treatment for the 123 patients with fracture-related infections Characteristics Staphylococci ( n = 83) Gram-negative Bacteria ( n = 29) Other ( n = 11) All organisms ( n = 123) Pathogen-directed intravenous antibiotic therapy No pathogen-directed parenteral antibiotic therapy 10 (12.1) 5 (17.3) 1 (9.1) 16 (13.0) Glycopeptide 41 (49.4) a 0 6 (54.5) 47 (38.2) Nafcillin 2 (2.4) 0 0 2 (1.7) Cefazolin 27 (32.5) a 1 (3.4) 0 28 (22.8) Extended-spectrum cephalosporins 0 7 (24.1) 1 (9.1) 8 (6.5) Piperacillin–tazobactam 1 (1.2) 9 (31.1) 1 (9.1) 11 (8.9) Other 2 (2.4) 7 (24.1) 2 (18.2) 11 (8.9) Duration of intravenous antibiotic therapy, days 21 (12–32) 20 (11–45) 18 (10–36) 21 (12–34) Pathogen-directed oral antibiotic therapy No pathogen-directed oral antibiotic therapy 34 (41.0) 11 (37.9) 7 (63.6) 52 (42.3) First generation cephalosporin 13 (15.7) 1 (3.5) 1 (9.1) 15 (12.2) Fluoroquinolone plus rifampin 12 (14.5) 0 0 12 (9.7) Fluoroquinolone 3 (3.6) 17 (58.6) 0 20 (16.3) Trimethoprim–sulfamethoxazole plus rifampin 5 (6.0) 0 0 5 (4.1) Trimethoprim–sulfamethoxazole plus fluoroquinolone 2 (2.4) 0 0 2 (1.6) Trimethoprim–sulfamethoxazole 9 (10.8) 0 0 9 (7.3) Clindamycin 2 (2.4) 0 0 2 (1.6) Other b 3 (3.6) b 0 3 (27.3) c 6 (4.9) All pathogen-directed antibiotic therapy Receipt of biofilm-active antibiotics 22 (26.5) 17 (58.6) 0 39 (31.7) Duration of antibiotic therapy, days 43 (28–73) 49 (34–94) 36 (20–50) 43 (28–73) < 6 weeks of antibiotic therapy 45 (54.2) 15 (51.7) 7 (63.6) 67 (54.5) 6–12 weeks of antibiotic therapy 22 (26.8) 7 (24.1) 3 (27.3) 32 (26.0) ≥ 12 weeks of antibiotic therapy 16 (19.5) 7 (24.1) 1 (9.1) 24 (19.5) Antibiotic-loaded bone cement 5 (6.2) 1 (3.6) 1 (10.0) 7 (5.9) Data are presented as numbers (%) or median (interquartile range), unless otherwise indicated. Abbreviations: FRI, fracture-related infection a Rifampin was used concurrently with cefazolin in two patients and vancomycin in one patient. b Clindamycin plus rifampin ( n = 1), fusidic acid plus rifampin ( n = 1), and linezolid ( n = 1) c Amoxicillin–clavulanate ( n = 3) Pathogen-directed oral antibiotics were prescribed after completion of intravenous antibiotic therapy in 71 (57.7%) patients. Thirty-nine (31.7%) patients received biofilm-active antibiotic therapy tailored to their antibiotic susceptibility. Among them, 22 received a rifampin-based combination for staphylococcal infections and 17 received fluoroquinolones for gram-negative infections. Among the 22 patients with staphylococcal infections, rifampin was used concurrently with intravenous antibiotics in three patients and with oral antibiotics in 19 patients. Intravenous companion drugs for rifampin included cefazolin in two patients and vancomycin in one patient. Oral companion drugs for rifampin included fluoroquinolone in 12 patients, trimethoprim–sulfamethoxazole in five, clindamycin in one, and fusidic acid in one. The median duration of total antibiotic therapy was 43 days (IQR, 28–73 days). Effect of ID consultation on antibiotic treatment ID specialists contributed to the management of 65 patients (52.9%) throughout the treatment period. Thirty-three patients (26.8%) received ID consultations that were terminated before the completion of therapy and 25 patients (20.3%) did not see an ID consultant during the course of treatment. The patients who participated in continuous ID consultations were more likely to receive pathogen-directed oral antibiotic therapy (76.9% vs. 36.2%; P < 0.001), biofilm-active antibiotics (52.3% vs. 8.6%; P < 0.001), and longer administration of antibiotic therapy (50.0 days vs. 26.0 days; P = 0.001) than those who did not receive such consultations. Table 3 illustrates how three ID consultation scenarios influenced antibiotic treatment. Table 3 Effects of infectious disease (ID) consultation on antibiotic therapy Characteristics ID consultation throughout the treatment period ( n = 65) Terminated ID consultation before end of treatment ( n = 33) No ID consultation ( n = 25) Initial pathogen-directed IV antibiotic therapy 51 (78.5) 20 (60.6) 14 (56.0) Pathogen-directed oral antibiotic therapy a,b 50 (76.9) 14 (42.4) 7 (28.0) Biofilm-active antibiotic therapy a,b 34 (52.3) 3 (9.1) 2 (8.0) Duration of intravenous antibiotic therapy, days 17 (11–31) 16 (10–29) 11 (0–41) Duration of all antibiotic therapy, days a, b 50 (31–88) 28 (13–54) 15 (0–48) ≥ 6 weeks of all antibiotic therapy a,b 39 (60.0) 10 (30.3) 17 (29.3) ≥ 12 weeks of all antibiotic therapy 18 (27.7) 4 (12.1) 2 (8.0) Data are presented as numbers. (%) or median (interquartile range), unless otherwise indicated. a P < 0.05 between continuous ID consult group and terminated ID consult group b P < 0.05 between continuous ID consult group and no ID consult group Therapeutic outcomes The median follow-up duration was 31 months (IQR, 7–39 months). Primary treatment failure during the initial treatment period was recorded in nine patients, of whom one required amputation and three experienced recurrence. Of the 114 patients who completed the initial treatment without primary failure, 31 experienced recurrence and one required amputation. Overall, 40 (32.5%) patients with FRIs experienced treatment failure. The median time to treatment failure was 109 days (IQR, 62–215 days), and treatment failure within one year was noted in 34 patients (85.0%). Treatment for early, delayed, and late infections failed in 36.4% (4/11), 33.3% (7/21), and 31.9% (26/91) of the patients, respectively ( P = 0.95). The failure rate was higher with debridement and implant retention than with implant removal (42.3% [30/71] vs. 19.2% [10/52], respectively; P = 0.01). Debridement and implant retention failed in 37.5% (3/8), 41.7% (5/12), and 43.1% (22/51) of early, delayed, and late FRI cases, respectively ( P = 0.99). Table 4 presents the results of the analyses of the parameters associated with treatment failure and recurrence in the patients with FRIs. The results of the univariate analyses indicated that Gustilo–Anderson grade 3 open fractures, implant retention, and no or early termination of ID consultation were associated with treatment failure. The multivariate analysis results indicated that factors associated with treatment failure included Gustilo–Anderson grade 3 open fracture (adjusted odds ratio [aOR], 3.82; 95% confidence interval [CI], 1.64–9.20; P = 0.002), implant retention (aOR, 3.01; 95% CI, 1.24–7.81; P = 0.02), and absence or early termination of ID consultation (aOR, 3.17; 95% CI, 1.36–7.71; P = 0.009). Table 4 Risk factors associated with treatment failure and recurrence in the 123 patients with fracture-related infections Variable Treatment success ( n = 83) Treatment failure ( n = 40) P -value No recurrence ( n = 89) Recurrence ( n = 34) P -value Patient characteristics Age, years 53 (34–66) 48 (29–66) 0.52 53 (34–66) 47 (29–66) 0.39 Male sex 62 (74.7) 33 (82.5) 0.46 66 (74.2) 29 (85.3) 0.28 Body mass index > 25 kg/m 2 27 (32.5) 19 (47.5) 0.16 31 (34.8) 15 (44.1) 0.46 Current smoking 27 (32.5) 8 (20.0) 0.22 28 (31.5) 7 (20.6) 0.33 Harmful alcohol consumption a 9 (10.8) 3 (7.5) 0.75 10 (11.2) 2 (5.9) 0.51 Diabetes mellitus 30 (36.1) 11 (27.5) 0.45 32 (36.0) 9 (26.5) 0.43 Malignancy 7 (8.4) 4 (10.0) 0.75 7 (7.9) 4 (11.8) 0.49 Cerebrovascular accident 6 (7.2) 2 (5.0) 0.99 7 (7.9) 1 (2.9) 0.44 Charlson Comorbidity Index score 0 46 (55.4) 26 (65.0) 0.42 49 (55.1) 23 (67.6) 0.29 1–3 24 (28.9) 11 (27.5) 0.99 27 (30.3) 8 (23.5) 0.60 ≥ 4 13 (15.7) 3 (7.5) 0.33 13 (14.6) 3 (8.8) 0.55 Characteristics of fracture Closed fracture 51 (61.4) 15 (37.5) 0.02 53 (59.6) 13 (38.2) 0.06 Open fracture, GA grade 1 1 (1.2) 0 0.99 1 (1.1) 0 0.99 Open fracture, GA grade 2 13 (15.7) 3 (7.0) 0.33 14 (15.7) 2 (5.9) 0.23 Open fracture, GA grade 3 18 (21.7) 22 (55.5) < 0.001 21 (23.6) 19 (55.9) 0.001 Comminuted fracture 46 (55.4) 19 (47.5) 0.53 48 (53.9) 17 (50.0) 0.85 Tibia and fibula 36 (43.4) 24 (60.0) 0.13 38 (42.7) 22 (64.7) 0.047 Femur 21 (25.3) 7 (17.5) 0.46 22 (24.7) 6 (17.6) 0.55 Ankle and foot 13 (15.7) 3 (7.5) 0.33 15 (16.9) 1 ( 2.9) 0.07 Radius and ulna 5 (6.0) 5 (12.5) 0.29 5 ( 5.6) 5 (14.7) 0.14 Humerus 4 (4.8) 0 0.30 4 ( 4.5) 0 0.58 Characteristics of infection Early infection 7 (8.4) 4 (10.0) 0.75 9 (10.1) 2 (5.9) 0.73 Delayed infection 14 (16.9) 7 (17.5) 0.99 15 (16.9) 6 (17.6) 0.99 Late infection 62 (74.7) 29 (72.5) 0.97 65 (73.0) 26 (76.5) 0.87 Fistula or sinus tract 11 (13.3) 3 (7.5) 0.55 11 (12.4) 3 ( 8.8) 0.76 Purulent discharge 26 (31.3) 18 (45.0) 0.20 29 (32.6) 15 (44.1) 0.33 Pain 60 (72.3) 25 (62.5) 0.37 62 (69.7) 23 (67.6) 0.99 Redness 13 (15.7) 6 (15.0) 0.99 13 (14.6) 6 (17.6) 0.89 Swelling 23 (27.7) 10 (25.0) 0.92 24 (27.0) 9 (26.5) 0.99 Local warmth 10 (12.0) 4 (10.0) 0.99 10 (11.2) 4 (11.8) 0.99 Fever (> 38°C) 5 (6.0) 3 (7.5) 0.71 6 (6.7) 2 (5.9) 0.99 WBC, ×10 9 /mL 7.4 (6.0–9.2) 7.3 (6.0–8.4) 0.45 7.4 (6.0–9.1) 7.3 (6.0–8.5) 0.56 ESR, mm/h 43 (25–79) 38 (23–67) 0.32 43 (25–77) 35 (18–68) 0.18 CRP, mg/dL 1.1 (0.3–4.5) 0.9 (0.5–2.4) 0.86 1.1 (0.4–4.3) 0.9 (0.5–2.1) 0.89 Management Implant retention 41 (49.4) 30 (75.0) 0.01 44 (49.4) 27 (79.4) 0.005 Antibiotic-loaded bone cement 5 (6.2) 2 (5.1) 0.99 5 (5.8) 2 (6.1) 0.99 Appropriate ID consultation 51 (61.4) 14 (35.0) 0.01 55 (61.8) 10 (29.4) 0.003 Pathogen-directed oral antibiotic therapy – – – 57 (64.0) 14 (41.2) 0.04 Biofilm-active antibiotic therapy – – – 35 (39.3) 4 (11.8) 0.007 Duration of antibiotic therapy 41 (24–72) 34 (10–61) 0.19 ≥ 6 weeks of antibiotics – – – 45 (50.6) 11 (32.4) 0.11 ≥ 12 weeks of antibiotics – – – 21 (23.6) 3 (8.8) 0.11 Data are presented as numbers (%), unless otherwise indicated. Abbreviations: CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; GA, Gustilo–Anderson; ID, infectious diseases; NC, not calculated; NE, not entered; WBC, white blood cells a Defined as consuming more than two standard drinks per day in men and more than one standard drink per day in women b Fracture at ulnar and pelvis c Rifampin was used concurrently with cefazolin in two patients and vancomycin in one patient. The results of the univariate analyses indicated that a Gustilo–Anderson grade 3 open fracture, implant retention, and lack of biofilm-active antibiotic use were associated with recurrence. The patients who received biofilm-active agents tailored to their antibiotic susceptibility experienced recurrence less frequently than those who did not receive these antibiotics (10.3% [4/39] vs. 35.7% [30/84], respectively; P = 0.007). This trend in the recurrence rate between patients treated with and without biofilm-active agents was evident in the implant retention group (14.3% [3/21] vs. 48.8% [24/50]; P = 0.02) but not in the implant removal group (5.6% [1/18] vs. 17.6% [6/34]; P = 0.40). The results of the Kaplan–Meier analysis further confirmed that the use of biofilm-active antibiotics was associated with improved recurrence-free survival in the implant retention group but not in the implant removal group (see Fig. 2 ). The multivariate analysis results indicated that the factors associated with recurrence included Gustilo–Anderson grade 3 open fracture (aOR, 3.56; 95% CI, 1.46–8.91; P = 0.006) and implant retention (aOR, 3.60; 95% CI, 1.39–10.31; P = 0.01). Biofilm-active antibiotic therapy was independently associated with a lower recurrence rate (aOR, 0.20; 95% CI, 0.05–0.61; P = 0.009). Discussion In this study, we examined factors that influenced treatment outcomes in 123 patients with FRIs. Our analysis revealed that implant retention, Gustilo–Anderson grade 3 open fractures, and inappropriate ID consultations were independently associated with treatment failure. Appropriate involvement of ID specialists correlated with frequent use of pathogen-directed oral antibiotics, biofilm-active antibiotics, and longer duration of antibiotic treatment. The use of biofilm-active antibiotics was independently associated with a lower recurrence rate. Data on the effect of ID specialist involvement in antibiotic prescriptions and outcomes in osteoarticular infections are limited. Lobata et al. demonstrated that involvement of ID specialists in the care of patients with osteomyelitis was significantly associated with longer courses of intravenous antibiotic therapy and a tendency toward higher limb salvage rates [ 17 ]. We found that continuous involvement of ID specialists in FRI management was associated with higher rates of switching to pathogen-directed oral and biofilm-active antibiotics, as well as with extended antibiotic therapy. Notably, inappropriate oral antibiotic selection was common not only when the patients were treated without ID consultation but also when the consulting services were interrupted. Biofilm-active antibiotic treatment was prescribed to only 9% of the patients in the terminated ID consultation group compared to 52% in the continuous ID consultation group. Based on our results, proactive ID consultation is recommended to mitigate the potential risk of treatment failure resulting from terminated consultations and inappropriate antibiotic selection. For instance, regular weekly audits of patients with FRIs by ID specialists, as part of a multidisciplinary team, may facilitate early intervention to ensure a timely switch from intravenous to appropriate anti-biofilm oral antibiotics. The data on the clinical benefits of biofilm-active antibiotic agents in FRI remains limited, although several observational studies have demonstrated their advantages in prosthetic joint infections (PJIs) [ 18 – 21 ]. Recently, Kuehl et al. reported significantly lower failure rates in patients who receive optimal biofilm-active therapy for late FRIs than in those who do not (7.7% vs. 50.0%) [ 11 ]. Our study also showed that biofilm-active antibiotic therapy was associated with lower recurrence rates, particularly in the implant retention group. In contrast, Corrigan et al. found that treatment success did not differ with the use of anti-biofilm agents in FRIs with retained implants [ 22 ]. Although the reason for this discrepancy is unclear, the rates of local antibiotic use between the studies may be a possible explanation. Local antibiotics were used in 58% of the patients in the study by Corrigan et al. but only in 6% of the patients in our study [ 22 ]. Local delivery can achieve high local antibiotic levels even in biofilm-embedded bacteria and minimize systemic toxicity risks [ 23 ]. Recently, Rupp et al. reported that a multidisciplinary treatment approach for FRIs was associated with a higher rate of local antibiotic use, as well as fewer amputations and revision surgeries [ 24 ]. Despite the association between appropriate ID consultation and longer duration of antibiotic therapy, we could not correlate the latter with improved outcomes. Although the optimal duration of antibiotic treatment for FRIs has not been thoroughly investigated, some authors suggest a 6-week course following implant removal and a 12-week regimen when the implant is retained [ 5 , 16 , 22 ]. In a previous study of 139 FRI cases, no significant difference was observed in treatment failure rates based on the total duration of antibiotic therapy: 3.8% ( 9 weeks) [ 25 ]. On the other hand, a small case series indicated that adequate surgery and local antibiotics may reduce the duration of systemic antibiotic use in FRIs [ 26 ] and PJIs [ 26 , 27 ]. The ongoing SOLARIO (Short or Long Antibiotic Regimens in Orthopaedics) randomized controlled trial aims to clarify this issue [29]. Further studies are required to determine the optimal duration of antibiotic treatment of FRIs. This study has certain limitations. First, the retrospective nature and single-center design may limit the generalizability of our findings to other settings with diverse patient populations, healthcare practices, and microbiological compositions. Second, the effect of anti-biofilm agents on improved outcomes might have been overestimated in our setting, as local antibiotic use was rare and the total duration of antibiotic therapy was relatively shorter than those in previous studies [ 11 , 22 ]. Third, the relatively small sample size compromised the statistical power of the study, potentially hindering the detection of differences within the early, delayed, and late infection subgroups. In conclusion, consistent involvement of ID specialists in FRI management was associated with higher rates of biofilm-active antibiotic use and prolonged antibiotic therapy. Biofilm-active antibiotics, when administered under the guidance of ID specialists, may contribute to improved outcomes in patients with FRIs. These observations suggest that ID specialists play a crucial role in optimizing antibiotic therapies for FRIs, potentially leading to more targeted and effective treatment strategies. Declarations Funding sources This study was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. RS-2023-00246999). Conflicts of interest The authors declare that they have no conflicts of interest. Ethics approval This study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the Institutional Review Board of Kyung Hee University Hospital (IRB number: 2023-11-060). Consent to participate and publish The Institutional Review Board of Kyung Hee University Hospital waived the need of obtaining informed consent. Data Availability Statement The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. Author Contribution D. Y. K., and K.-H. P. contributed to the conception and design of the study. D. Y. K., K. -C. K., and K.-H. P. collected the data. D. Y. K., K. -C. K., and K.-H. P. analyzed and interpreted the data. D. Y. K., and K.-H. P. drafted the manuscript. C. H. P., J.-H. B., B. O. J., K. H. R., G. K., Y. -M. L. and M. S. L, critically reviewed the manuscript. All authors read and approved the final version of the manuscript. Data Availability The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. References Trampuz, A. & Zimmerli, W. Diagnosis and treatment of infections associated with fracture-fixation devices. Injury 37 (Suppl 2), S59–66 (2006). Court-Brown, C. M. & McQueen, M. M. Global Forum: Fractures in the Elderly. J. Bone Joint Surg. Am. 98 (9), e36 (2016). Fang, C. et al. Infection after fracture osteosynthesis - Part I. J. Orthop. Surg. (Hong Kong) . 25 (1), 2309499017692712 (2017). Metsemakers, W. J. et al. Infection after fracture fixation: Current surgical and microbiological concepts. Injury 49 (3), 511–522 (2018). Depypere, M. et al. Pathogenesis and management of fracture-related infection. Clin. Microbiol. Infect. 26 (5), 572–578 (2020). Metsemakers, W. J. et al. General treatment principles for fracture-related infection: recommendations from an international expert group. Arch. Orthop. Trauma. Surg. 140 (8), 1013–1027 (2020). Iliadis, A. D. et al. Current concepts in the prevention, diagnosis and treatment of fracture-related infection (FRI). Eur. J. Orthop. Surg. Traumatol. 31 (5), 957–966 (2021). Metsemakers, W. J. et al. Fracture-related infection: A consensus on definition from an international expert group. Injury 49 (3), 505–510 (2018). Pulcini, C., Botelho-Nevers, E., Dyar, O. J. & Harbarth, S. The impact of infectious disease specialists on antibiotic prescribing in hospitals. Clin. Microbiol. Infect. 20 (10), 963–972 (2014). Willenegger, H. & Roth, B. [Treatment tactics and late results in early infection following osteosynthesis]. Unfallchirurgie 12 (5), 241–246 (1986). Kuehl, R. et al. Time-dependent differences in management and microbiology of orthopaedic internal fixation-associated infections: an observational prospective study with 229 patients. Clin. Microbiol. Infect. 25 (1), 76–81 (2019). Sundararajan, V. et al. New ICD-10 version of the Charlson comorbidity index predicted in-hospital mortality. J. Clin. Epidemiol. 57 (12), 1288–1294 (2004). Charlson, M. E., Pompei, P., Ales, K. L. & MacKenzie, C. R. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J. Chronic Dis. 40 (5), 373–383 (1987). Walenkamp, G. H., Kleijn, L. L. & de Leeuw, M. Osteomyelitis treated with gentamicin-PMMA beads: 100 patients followed for 1–12 years. Acta Orthop. Scand. 69 (5), 518–522 (1998). Metsemakers, W. J. et al. Evidence-Based Recommendations for Local Antimicrobial Strategies and Dead Space Management in Fracture-Related Infection. J. Orthop. Trauma. 34 (1), 18–29 (2020). Depypere, M. et al. Recommendations for Systemic Antimicrobial Therapy in Fracture-Related Infection: A Consensus From an International Expert Group. J. Orthop. Trauma. 34 (1), 30–41 (2020). Lobati, F., Herndon, B. & Bamberger, D. Osteomyelitis: etiology, diagnosis, treatment and outcome in a public versus a private institution. Infection 29 (6), 333–336 (2001). Zimmerli, W., Widmer, A. F., Blatter, M., Frei, R. & Ochsner, P. E. Role of rifampin for treatment of orthopedic implant-related staphylococcal infections: a randomized controlled trial. Foreign-Body Infection (FBI) Study Group. JAMA 279 (19), 1537–1541 (1998). Beldman, M. et al. If, When, and How to Use Rifampin in Acute Staphylococcal Periprosthetic Joint Infections, a Multicentre Observational Study. Clin. Infect. Dis. 73 (9), 1634–1641 (2021). Aboltins, C. A. et al. Gram-negative prosthetic joint infection treated with debridement, prosthesis retention and antibiotic regimens including a fluoroquinolone. Clin. Microbiol. Infect. 17 (6), 862–867 (2011). Lora-Tamayo, J. et al. A large multicenter study of methicillin-susceptible and methicillin-resistant Staphylococcus aureus prosthetic joint infections managed with implant retention. Clin. Infect. Dis. 56 (2), 182–194 (2013). Corrigan, R., Sliepen, J., Rentenaar, R. J., Hietbrink, F. I. J. & Atkins, F. The effect of guideline-based antimicrobial therapy on the outcome of fracture-related infections (EAT FRI Study). J. Infect. 86 (3), 227–232 (2023). ter Boo, G. J., Grijpma, D. W., Moriarty, T. F., Richards, R. G. & Eglin, D. Antimicrobial delivery systems for local infection prophylaxis in orthopedic- and trauma surgery. Biomaterials 52 , 113–125 (2015). Rupp, M. et al. Multidisciplinary Treatment of Fracture-Related Infection Has a Positive Impact on Clinical Outcome-A Retrospective Case Control Study at a Tertiary Referral Center. Antibiot. (Basel) ; 12 (2). (2023). Al-Mayahi, M. et al. Remission rate of implant-related infections following revision surgery after fractures. Int. Orthop. 37 (11), 2253–2258 (2013). Stockley, I., Mockford, B. J., Hoad-Reddick, A. & Norman, P. The use of two-stage exchange arthroplasty with depot antibiotics in the absence of long-term antibiotic therapy in infected total hip replacement. J. Bone Joint Surg. Br. 90 (2), 145–148 (2008). Nelson, C. L. et al. A comparison of gentamicin-impregnated polymethylmethacrylate bead implantation to conventional parenteral antibiotic therapy in infected total hip and knee arthroplasty. Clin. Orthop. Relat. Res. (295):96–101. (1993). Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6223447","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":455575212,"identity":"515bfe51-a454-455d-b84d-225cb772a0c5","order_by":0,"name":"Dong Youn Kim","email":"","orcid":"","institution":"Kyung Hee University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Dong","middleName":"Youn","lastName":"Kim","suffix":""},{"id":455575213,"identity":"38fcc787-a19e-49d6-9e26-a5b82fb74351","order_by":1,"name":"Kyung-Chung Kang","email":"","orcid":"","institution":"Kyung Hee University 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Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mi","middleName":"Suk","lastName":"Lee","suffix":""}],"badges":[],"createdAt":"2025-03-14 03:53:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6223447/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6223447/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-025-22165-1","type":"published","date":"2025-11-03T15:57:17+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":82791567,"identity":"0d33b495-207b-413a-8bb4-871b8216f894","added_by":"auto","created_at":"2025-05-15 10:12:12","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":71723,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of the patient inclusion process and outcomes of fracture-related infections\u003c/p\u003e","description":"","filename":"floatimage135.png","url":"https://assets-eu.researchsquare.com/files/rs-6223447/v1/a0ca31dcfdd1e9be39f5e840.png"},{"id":82791568,"identity":"02fd3f50-6173-402c-8cfe-3bb8ce36f73a","added_by":"auto","created_at":"2025-05-15 10:12:12","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":87482,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier plots comparing the recurrence-free survival of patients treated with or without biofilm-active antibiotics in cases of implant retention and removal\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6223447/v1/a3c792dd5138c516530bf92e.png"},{"id":95563977,"identity":"cc2aa4ae-a79c-4b42-a1b9-54c607741949","added_by":"auto","created_at":"2025-11-10 16:05:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1642992,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6223447/v1/a5a97e81-9cfc-4f58-ac0a-e479b2cd0aed.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Impact of infectious disease specialist consultations on antibiotic treatment and outcomes of fracture-related infections ","fulltext":[{"header":"Introduction","content":"\u003cp\u003eFracture-related infection (FRI) is a critical complication of trauma surgery that significantly affects patient outcomes and poses risks such as permanent functional loss or amputation. The prevalence of FRI is considerable and estimated at approximately 1\u0026ndash;2% in closed fractures with internal fixation and up to 30% in open fractures [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. These rates are expected to increase with the growing number of fracture-related surgeries, particularly in the older adult population [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe management of FRIs is inherently complex owing to several factors. FRIs develop from infections in orthopedic devices inserted after trauma and are often accompanied by soft tissue and vascular damage. This damage can impair wound healing and the local blood supply, hindering the delivery of antibiotics and immune cells to the site of infection. The variability in fracture types and locations further adds to the complexity. Surgical treatment often involves multiple procedures, including debridement (removal of infected and necrotic tissue), stabilization of the fracture, and removal and replacement of hardware. Maintaining fracture stability is crucial, and complete fixative removal in FRIs is feasible only after bone union is achieved. In patients who require orthopedic devices for stabilization, optimal antibiotics should be carefully selected to eradicate biofilm-embedded bacteria on the surface of the orthopedic devices and to prevent recurrence [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThese complexities require collaboration among multiple medical disciplines, including trauma, orthopedics, and vascular surgeons, as well as infectious disease (ID) specialists, microbiologists, and pharmacists [\u003cspan additionalcitationids=\"CR5 CR6 CR7\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. ID specialists play a critical role in selecting optimal initial antibiotics based on diagnostic test results and patient conditions. Furthermore, their involvement is essential throughout the treatment period to determine the timing for transitioning from intravenous to suitable oral antibiotics, assess treatment tolerability, and provide alternative therapeutic options when necessary. Multiple studies encompassing a wide range of infections and hospital settings showed that patients who received ID consultations were prescribed more appropriate antibiotics and had better prognoses [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. However, limited data exist regarding the role of ID specialists in the management of orthopedic device-related infections. This study aimed to evaluate the impact of ID specialist involvement on antibiotic treatment and outcomes of FRIs.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003eThis study was conducted at an 850-bed tertiary care academic center. We retrospectively reviewed the medical charts of all consecutively enrolled adult patients with suspected FRIs between January 2008 and December 2022. The study was approved by the Institutional Review Board of Kyung Hee University Hospital (IRB number: 2023-11-060). Due to the retrospective nature of the study, the Institutional Review Board of Kyung Hee University Hospital waived the need of obtaining informed consent.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eInclusion and exclusion criteria\u003c/h3\u003e\n\u003cp\u003ePatients with definite FRIs, as defined by the consensus of an international expert group [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], were included. Briefly, patients were considered to have a definite FRI if they had (i) fistula, sinus, or wound breakdown; (ii) purulent drainage from the wound or pus exudation during surgery; or (iii) phenotypically indistinguishable pathogens identified through cultures of at least two separate deep-tissue specimens [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. To ensure clarity of the relationship between antimicrobial selection and treatment outcomes, only microbiologically confirmed cases were assessed in this study. Other reasons for exclusion were incomplete medical records and death before the completion of the antibiotic therapy. FRIs were classified as early (0\u0026ndash;2 weeks after implantation), delayed (3\u0026ndash;10 weeks), or late (\u0026ge;\u0026thinsp;10 weeks) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003e We retrospectively reviewed the medical records for demographic information, underlying illness/condition, characteristics of fractures and FRIs, medical and surgical treatments, and clinical outcomes. To quantify the overall comorbidity burden, we calculated the Charlson Comorbidity Index (CCI) scores using codes from the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eTreatment\u003c/h3\u003e\n\u003cp\u003eThe decision for surgical therapy, including implant retention and use of local antibiotics, was at the discretion of the treating physicians. Retaining the implant requires construct stability that facilitates bone healing, adequate surgical debridement, and soft tissue coverage [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The fixation implant was removed if the bone had healed or exchanged if the bone required further stabilization [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Local elution of antibiotics was achieved using antibiotic-impregnated polymethyl methacrylate (PMMA) cement beads and spacers [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Biofilm-active antibiotic therapy was defined as the administration of a rifampin-based combination for staphylococci or fluoroquinolone for gram-negative bacteria. The intravenous companion drugs for rifampin include nafcillin, cefazolin, vancomycin, and teicoplanin. The oral companion drugs for rifampin include fluoroquinolones, trimethoprim\u0026ndash;sulfamethoxazole, fusidic acid, clindamycin, and linezolid [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The duration of antibiotic therapy was determined based solely on the antimicrobial agents that were appropriate for the isolated organisms and their susceptibility profiles.\u003c/p\u003e\n\u003ch3\u003eID consultation\u003c/h3\u003e\n\u003cp\u003eThe decision to conduct ID consultations was made by the treating physicians. We divided the patients into two groups to assess the appropriateness of these consultations. The appropriate ID consultation group consisted of patients who received continuous ID consultations throughout their treatment, until the completion of antimicrobial therapy. The inappropriate ID consultation group included patients who either did not receive any ID consultations or whose consultations were prematurely discontinued before the completion of antibiotic therapy.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eOutcomes\u003c/h2\u003e \u003cp\u003eTreatment failure was defined as primary failure, infection recurrence, and/or amputation after surgery. Primary failure was defined as new surgical debridement after the initial definite surgery for infection or skin coverage before the end of antibiotic treatment because of signs of uncontrolled infection. Recurrence was defined as unplanned surgery after the completion of antibiotic therapy because of infection recurrence based on the aforementioned definite criteria for FRIs [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Detection of the same pathogen(s) as in the first episode, as well as a new or no pathogen, was interpreted as recurrence, unless conclusive evidence favored new hematogenous seeding after bloodstream infection.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStatistical analyses\u003c/h3\u003e\n\u003cp\u003eAll analyses were performed using the R statistical software (version 4.3.3; R Foundation for Statistical Computing, Vienna, Austria). Categorical variables were compared using the chi-square test or Fisher\u0026rsquo;s exact test, and continuous variables were compared using the Mann\u0026ndash;Whitney U test. Univariate and multivariate analyses of the parameters predictive of treatment failure and recurrence were performed using logistic regression. All variables with a significant result in the univariate analysis were considered in the multivariate logistic regression model. Antibiotic selection and duration of use were included in the multivariate model for recurrence but not in the model for treatment failure, as primary failures occurred before the completion of antibiotic therapy. The treatment failure- and recurrence-free survival rates were estimated using the Kaplan\u0026ndash;Meier method, and the survival curves of the two groups were compared using the log-rank test. All tests for statistical significance were two-tailed, and \u003cem\u003eP\u003c/em\u003e-values\u0026thinsp;\u0026le;\u0026thinsp;0.05 were considered to indicate statistical significance.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eDuring the study period, FRI was suspected in 189 patients. Among these, 151 met the predefined criteria for definite FRI. Of the 151 definite FRIs, 28 were excluded for the following reasons: no microbiological confirmation (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;21), loss to follow-up within one year (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;4), incomplete medical records (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2), and nontuberculous mycobacterial infection (n\u0026thinsp;=\u0026thinsp;1). Ultimately, data from 123 cases of definite FRIs were included in the final analysis, of which 11 cases (8.9%) were of early FRI, 21 (17.1%) of delayed FRI, and 91 (74.0%) of late FRI (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). All except one of the 18 patients in the implant exchange cohort underwent one-stage exchange. Consequently, we classified the exchange group as part of the implant retention group in the outcome analysis.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u0026rsquo; characteristics\u003c/h2\u003e \u003cp\u003eThe clinical characteristics of the 123 patients with FRIs are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The median age of the participants was 50 years (interquartile range [IQR], 33\u0026ndash;66 years) and 95 (77.2%) were male. Forty-one patients (33.3%) had diabetes mellitus and 11 (8.9%) had underlying malignancies. Fifty-three (43.1%) of the 123 patients with infections were managed with implant retention, 18 (14.6%) with implant exchange, and 52 (42.3%) with implant removal (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of the 123 patients with microbiologically diagnosed fracture-related infections\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEarly FRI\u003c/p\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;11)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDelayed FRI\u003c/p\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;21)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLate FRI\u003c/p\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;91)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAll cases\u003c/p\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;123)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient characteristics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50 (32\u0026ndash;65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45 (23\u0026ndash;63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50 (34\u0026ndash;66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50 (33\u0026ndash;66)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale sex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (54.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (76.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e73 (80.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e95 (77.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody mass index\u0026thinsp;\u0026ge;\u0026thinsp;25 kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (63.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (28.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33 (36.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e46 (37.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCurrent smoker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (45.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23 (25.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e35 (28.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHarmful alcohol consumption\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (45.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (19.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (6.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15 (12.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (27.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31 (34.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e41 (33.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMalignancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (4.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (11.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11 (8.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebrovascular accident\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (18.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (6.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8 (6.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharlson Comorbidity Index score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (63.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (57.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e53 (58.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e72 (58.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u0026ndash;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (27.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (33.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25 (27.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e35 (28.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (9.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16 (13.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics of fracture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInjury severity of fracture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClosed fracture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (45.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (61.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48 (52.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e66 (53.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOpen fracture, GA grade 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (0.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOpen fracture, GA grade 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (9.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16 (13.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOpen fracture, GA grade 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (36.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (28.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30 (33.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40 (32.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComminuted fracture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (90.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41 (45.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e65 (52.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSite of fracture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTibia and fibula\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (45.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (47.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e45 (49.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e60 (48.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemur\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (4.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27 (29.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e28 (22.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnkle and foot\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (36.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (9.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (11.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16 (13.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadius and ulna\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (9.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 (8.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHumerus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (9.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (3.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (19.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (3.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultiple sites\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (0.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics of infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFistula or sinus tract\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (4.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14 (11.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePurulent discharge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (72.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29 (31.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e44 (35.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (54.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (85.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e61 (67.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e85 (69.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRedness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (18.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (9.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (16.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19 (15.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSwelling\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (36.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (23.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24 (26.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e33 (26.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLocal warmth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (19.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (11.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14 (11.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFever (\u0026gt;\u0026thinsp;38\u0026deg;C)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8 (6.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC, \u0026times;10\u003csup\u003e9\u003c/sup\u003e/mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.6 (4.4\u0026ndash; 7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.0 (7.4\u0026ndash; 9.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.2 (6.0\u0026ndash; 8.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.4 (6.0\u0026ndash; 9.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eESR, mm/h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (22\u0026ndash;62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65 (27\u0026ndash;86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39 (24\u0026ndash;70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e43 (24\u0026ndash;74)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP, mg/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.9 (0.9\u0026ndash; 8.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.1 (0.5\u0026ndash; 7.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9 (0.4\u0026ndash; 2.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.1 (0.4\u0026ndash; 4.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCausative pathogens\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eStaphylococcus aureus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (38.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e56 (61.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e65 (52.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eMethicillin-susceptible S. aureus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (9.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 (22.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e22 (17.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eMethicillin-resistant S. aureus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (28.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36 (39.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e43 (35.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoagulase-negative staphylococci\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (27.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (13.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17 (14.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eEnterococcus\u003c/em\u003e species\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (2.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eEnterobacteriaceae\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (36.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (4.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (5.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 (8.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (9.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17 (13.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eStenotrophomonas maltophilia\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (1.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (4.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (3.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePolymicrobial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (4.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (2.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (3.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eData are presented as numbers (%) or median (interquartile range), unless otherwise indicated.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eAbbreviations: CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; GA, Gustilo\u0026ndash;Anderson; FRI, fracture-related infection; WBC, white blood cells\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ea\u003c/sup\u003e Defined as consuming more than two standard drinks per day in men and more than one standard drink per day in women\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe most common site of fracture was the tibia/fibula (48.8%), followed by the femur (22.8%) and ankle/foot (13.0%). \u003cem\u003eStaphylococcus aureus\u003c/em\u003e was the most common causative pathogen (52.8%), followed by coagulase-negative staphylococci (14.6%), \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e (13.8%), and \u003cem\u003eEnterobacteriaceae\u003c/em\u003e (8.1%). Implants were initially removed in 27.3% (3/11) of the patients with early FRIs, 42.9% (9/21) with delayed FRIs, and 44.0% (40/91) of patients with late FRIs (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eAntibiotic treatment\u003c/h2\u003e \u003cp\u003eThe types, routes, and duration of antimicrobial therapy received for FRIs are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The median duration of intravenous antibiotic therapy was 21 days (IQR, 12\u0026ndash;34 days). Among the 83 patients with staphylococcal infections, primary parenteral therapy consisted of glycopeptides in 41 (49.4%) and cefazolin in 27 (32.5%). Among the 29 patients with gram-negative bacterial infections, primary parenteral therapy consisted of piperacillin\u0026ndash;tazobactam in nine (31.1%) and extended-spectrum cephalosporins in seven (24.1%).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAntimicrobial treatment for the 123 patients with fracture-related infections\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStaphylococci\u003c/p\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;83)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGram-negative Bacteria\u003c/p\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;29)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;11)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAll organisms\u003c/p\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;123)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathogen-directed intravenous antibiotic therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo pathogen-directed parenteral antibiotic therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (12.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (17.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16 (13.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlycopeptide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41 (49.4)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (54.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e47 (38.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNafcillin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (1.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCefazolin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (32.5)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e28 (22.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtended-spectrum cephalosporins\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (24.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8 (6.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePiperacillin\u0026ndash;tazobactam\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (31.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11 (8.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (24.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (18.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11 (8.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of intravenous antibiotic therapy, days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (12\u0026ndash;32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (11\u0026ndash;45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18 (10\u0026ndash;36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21 (12\u0026ndash;34)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathogen-directed oral antibiotic therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo pathogen-directed oral antibiotic therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (41.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (37.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (63.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e52 (42.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFirst generation cephalosporin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (15.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15 (12.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFluoroquinolone plus rifampin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (14.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12 (9.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFluoroquinolone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (58.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20 (16.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTrimethoprim\u0026ndash;sulfamethoxazole plus rifampin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (6.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5 (4.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTrimethoprim\u0026ndash;sulfamethoxazole plus fluoroquinolone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (1.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTrimethoprim\u0026ndash;sulfamethoxazole\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (10.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9 (7.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClindamycin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (1.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (3.6)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (27.3)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (4.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAll pathogen-directed antibiotic therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReceipt of biofilm-active antibiotics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (26.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (58.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e39 (31.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of antibiotic therapy, days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43 (28\u0026ndash;73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49 (34\u0026ndash;94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36 (20\u0026ndash;50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e43 (28\u0026ndash;73)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;6 weeks of antibiotic therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45 (54.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (51.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (63.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e67 (54.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u0026ndash;12 weeks of antibiotic therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (26.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (24.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (27.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e32 (26.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;12 weeks of antibiotic therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (19.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (24.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24 (19.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntibiotic-loaded bone cement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7 (5.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eData are presented as numbers (%) or median (interquartile range), unless otherwise indicated.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eAbbreviations: FRI, fracture-related infection\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ea\u003c/sup\u003e Rifampin was used concurrently with cefazolin in two patients and vancomycin in one patient.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003eb\u003c/sup\u003e Clindamycin plus rifampin (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1), fusidic acid plus rifampin (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1), and linezolid (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1)\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ec\u003c/sup\u003e Amoxicillin\u0026ndash;clavulanate (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;3)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePathogen-directed oral antibiotics were prescribed after completion of intravenous antibiotic therapy in 71 (57.7%) patients. Thirty-nine (31.7%) patients received biofilm-active antibiotic therapy tailored to their antibiotic susceptibility. Among them, 22 received a rifampin-based combination for staphylococcal infections and 17 received fluoroquinolones for gram-negative infections. Among the 22 patients with staphylococcal infections, rifampin was used concurrently with intravenous antibiotics in three patients and with oral antibiotics in 19 patients. Intravenous companion drugs for rifampin included cefazolin in two patients and vancomycin in one patient. Oral companion drugs for rifampin included fluoroquinolone in 12 patients, trimethoprim\u0026ndash;sulfamethoxazole in five, clindamycin in one, and fusidic acid in one. The median duration of total antibiotic therapy was 43 days (IQR, 28\u0026ndash;73 days).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eEffect of ID consultation on antibiotic treatment\u003c/h2\u003e \u003cp\u003eID specialists contributed to the management of 65 patients (52.9%) throughout the treatment period. Thirty-three patients (26.8%) received ID consultations that were terminated before the completion of therapy and 25 patients (20.3%) did not see an ID consultant during the course of treatment. The patients who participated in continuous ID consultations were more likely to receive pathogen-directed oral antibiotic therapy (76.9% vs. 36.2%; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), biofilm-active antibiotics (52.3% vs. 8.6%; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and longer administration of antibiotic therapy (50.0 days vs. 26.0 days; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001) than those who did not receive such consultations. Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e illustrates how three ID consultation scenarios influenced antibiotic treatment.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEffects of infectious disease (ID) consultation on antibiotic therapy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eID consultation throughout the treatment period\u003c/p\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;65)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTerminated ID consultation before end of treatment\u003c/p\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;33)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo ID consultation\u003c/p\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;25)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInitial pathogen-directed IV antibiotic therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51 (78.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (60.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (56.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathogen-directed oral antibiotic therapy\u003csup\u003ea,b\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50 (76.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (42.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (28.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBiofilm-active antibiotic therapy\u003csup\u003ea,b\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (52.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (8.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of intravenous antibiotic therapy, days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (11\u0026ndash;31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (10\u0026ndash;29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (0\u0026ndash;41)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of all antibiotic therapy, days\u003csup\u003ea, b\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50 (31\u0026ndash;88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (13\u0026ndash;54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (0\u0026ndash;48)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;6 weeks of all antibiotic therapy\u003csup\u003ea,b\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (60.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (30.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17 (29.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;12 weeks of all antibiotic therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (27.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (12.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (8.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are presented as numbers. (%) or median (interquartile range), unless otherwise indicated.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003ea\u003c/sup\u003e \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 between continuous ID consult group and terminated ID consult group\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003eb\u003c/sup\u003e \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 between continuous ID consult group and no ID consult group\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eTherapeutic outcomes\u003c/h2\u003e \u003cp\u003eThe median follow-up duration was 31 months (IQR, 7\u0026ndash;39 months). Primary treatment failure during the initial treatment period was recorded in nine patients, of whom one required amputation and three experienced recurrence. Of the 114 patients who completed the initial treatment without primary failure, 31 experienced recurrence and one required amputation. Overall, 40 (32.5%) patients with FRIs experienced treatment failure. The median time to treatment failure was 109 days (IQR, 62\u0026ndash;215 days), and treatment failure within one year was noted in 34 patients (85.0%). Treatment for early, delayed, and late infections failed in 36.4% (4/11), 33.3% (7/21), and 31.9% (26/91) of the patients, respectively (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.95). The failure rate was higher with debridement and implant retention than with implant removal (42.3% [30/71] vs. 19.2% [10/52], respectively; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.01). Debridement and implant retention failed in 37.5% (3/8), 41.7% (5/12), and 43.1% (22/51) of early, delayed, and late FRI cases, respectively (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.99).\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e presents the results of the analyses of the parameters associated with treatment failure and recurrence in the patients with FRIs. The results of the univariate analyses indicated that Gustilo\u0026ndash;Anderson grade 3 open fractures, implant retention, and no or early termination of ID consultation were associated with treatment failure. The multivariate analysis results indicated that factors associated with treatment failure included Gustilo\u0026ndash;Anderson grade 3 open fracture (adjusted odds ratio [aOR], 3.82; 95% confidence interval [CI], 1.64\u0026ndash;9.20; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002), implant retention (aOR, 3.01; 95% CI, 1.24\u0026ndash;7.81; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02), and absence or early termination of ID consultation (aOR, 3.17; 95% CI, 1.36\u0026ndash;7.71; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.009).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRisk factors associated with treatment failure and recurrence in the 123 patients with fracture-related infections\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTreatment\u003c/p\u003e \u003cp\u003esuccess\u003c/p\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;83)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTreatment\u003c/p\u003e \u003cp\u003efailure\u003c/p\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo recurrence\u003c/p\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;89)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eRecurrence\u003c/p\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient characteristics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53 (34\u0026ndash;66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48 (29\u0026ndash;66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e53 (34\u0026ndash;66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e47 (29\u0026ndash;66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.39\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale sex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62 (74.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33 (82.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e66 (74.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e29 (85.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody mass index\u0026thinsp;\u0026gt;\u0026thinsp;25 kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (32.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (47.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e31 (34.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15 (44.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCurrent smoking\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (32.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e28 (31.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7 (20.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHarmful alcohol consumption\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (10.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (7.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 (11.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2 (5.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.51\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (36.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (27.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e32 (36.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9 (26.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.43\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMalignancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (8.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7 (7.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4 (11.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.49\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebrovascular accident\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (7.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7 (7.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.44\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharlson Comorbidity Index score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46 (55.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (65.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e49 (55.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e23 (67.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u0026ndash;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (28.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (27.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e27 (30.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8 (23.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.60\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (15.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (7.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13 (14.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3 (8.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics of fracture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClosed fracture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51 (61.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (37.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e53 (59.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13 (38.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOpen fracture, GA grade 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOpen fracture, GA grade 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (15.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (7.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14 (15.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2 (5.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOpen fracture, GA grade 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (21.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (55.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21 (23.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e19 (55.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComminuted fracture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46 (55.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (47.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e48 (53.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e17 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.85\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTibia and fibula\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (43.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (60.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e38 (42.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e22 (64.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.047\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemur\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (25.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (17.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e22 (24.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6 (17.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnkle and foot\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (15.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (7.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15 (16.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 ( 2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadius and ulna\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (6.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5 ( 5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5 (14.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHumerus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (4.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 ( 4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics of infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEarly infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (8.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9 (10.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2 (5.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.73\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDelayed infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (16.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (17.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15 (16.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6 (17.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLate infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62 (74.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (72.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e65 (73.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e26 (76.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.87\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFistula or sinus tract\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (13.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (7.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11 (12.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3 ( 8.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.76\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePurulent discharge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (31.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (45.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e29 (32.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15 (44.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60 (72.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (62.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e62 (69.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e23 (67.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRedness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (15.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13 (14.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6 (17.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.89\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSwelling\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (27.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24 (27.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9 (26.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLocal warmth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (12.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 (11.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4 (11.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFever (\u0026gt;\u0026thinsp;38\u0026deg;C)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (6.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (7.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2 (5.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC, \u0026times;10\u003csup\u003e9\u003c/sup\u003e/mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.4 (6.0\u0026ndash;9.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.3 (6.0\u0026ndash;8.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.4 (6.0\u0026ndash;9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.3 (6.0\u0026ndash;8.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.56\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eESR, mm/h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43 (25\u0026ndash;79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38 (23\u0026ndash;67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e43 (25\u0026ndash;77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e35 (18\u0026ndash;68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP, mg/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.1 (0.3\u0026ndash;4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.9 (0.5\u0026ndash;2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.1 (0.4\u0026ndash;4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.9 (0.5\u0026ndash;2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.89\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eManagement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImplant retention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41 (49.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (75.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e44 (49.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e27 (79.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntibiotic-loaded bone cement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (5.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5 (5.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2 (6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAppropriate ID consultation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51 (61.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (35.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e55 (61.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10 (29.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathogen-directed oral antibiotic therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e57 (64.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e14 (41.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBiofilm-active antibiotic therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e35 (39.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4 (11.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of antibiotic therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e41 (24\u0026ndash;72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e34 (10\u0026ndash;61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.19\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;6 weeks of antibiotics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e45 (50.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11 (32.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;12 weeks of antibiotics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21 (23.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3 (8.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eData are presented as numbers (%), unless otherwise indicated.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eAbbreviations: CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; GA, Gustilo\u0026ndash;Anderson; ID, infectious diseases; NC, not calculated; NE, not entered; WBC, white blood cells\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003csup\u003ea\u003c/sup\u003e Defined as consuming more than two standard drinks per day in men and more than one standard drink per day in women\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003csup\u003eb\u003c/sup\u003e Fracture at ulnar and pelvis\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003csup\u003ec\u003c/sup\u003e Rifampin was used concurrently with cefazolin in two patients and vancomycin in one patient.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe results of the univariate analyses indicated that a Gustilo\u0026ndash;Anderson grade 3 open fracture, implant retention, and lack of biofilm-active antibiotic use were associated with recurrence. The patients who received biofilm-active agents tailored to their antibiotic susceptibility experienced recurrence less frequently than those who did not receive these antibiotics (10.3% [4/39] vs. 35.7% [30/84], respectively; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.007). This trend in the recurrence rate between patients treated with and without biofilm-active agents was evident in the implant retention group (14.3% [3/21] vs. 48.8% [24/50]; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02) but not in the implant removal group (5.6% [1/18] vs. 17.6% [6/34]; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.40). The results of the Kaplan\u0026ndash;Meier analysis further confirmed that the use of biofilm-active antibiotics was associated with improved recurrence-free survival in the implant retention group but not in the implant removal group (see Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The multivariate analysis results indicated that the factors associated with recurrence included Gustilo\u0026ndash;Anderson grade 3 open fracture (aOR, 3.56; 95% CI, 1.46\u0026ndash;8.91; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.006) and implant retention (aOR, 3.60; 95% CI, 1.39\u0026ndash;10.31; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.01). Biofilm-active antibiotic therapy was independently associated with a lower recurrence rate (aOR, 0.20; 95% CI, 0.05\u0026ndash;0.61; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.009).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we examined factors that influenced treatment outcomes in 123 patients with FRIs. Our analysis revealed that implant retention, Gustilo\u0026ndash;Anderson grade 3 open fractures, and inappropriate ID consultations were independently associated with treatment failure. Appropriate involvement of ID specialists correlated with frequent use of pathogen-directed oral antibiotics, biofilm-active antibiotics, and longer duration of antibiotic treatment. The use of biofilm-active antibiotics was independently associated with a lower recurrence rate.\u003c/p\u003e \u003cp\u003eData on the effect of ID specialist involvement in antibiotic prescriptions and outcomes in osteoarticular infections are limited. Lobata et al. demonstrated that involvement of ID specialists in the care of patients with osteomyelitis was significantly associated with longer courses of intravenous antibiotic therapy and a tendency toward higher limb salvage rates [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. We found that continuous involvement of ID specialists in FRI management was associated with higher rates of switching to pathogen-directed oral and biofilm-active antibiotics, as well as with extended antibiotic therapy. Notably, inappropriate oral antibiotic selection was common not only when the patients were treated without ID consultation but also when the consulting services were interrupted. Biofilm-active antibiotic treatment was prescribed to only 9% of the patients in the terminated ID consultation group compared to 52% in the continuous ID consultation group. Based on our results, proactive ID consultation is recommended to mitigate the potential risk of treatment failure resulting from terminated consultations and inappropriate antibiotic selection. For instance, regular weekly audits of patients with FRIs by ID specialists, as part of a multidisciplinary team, may facilitate early intervention to ensure a timely switch from intravenous to appropriate anti-biofilm oral antibiotics.\u003c/p\u003e \u003cp\u003eThe data on the clinical benefits of biofilm-active antibiotic agents in FRI remains limited, although several observational studies have demonstrated their advantages in prosthetic joint infections (PJIs) [\u003cspan additionalcitationids=\"CR19 CR20\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Recently, Kuehl et al. reported significantly lower failure rates in patients who receive optimal biofilm-active therapy for late FRIs than in those who do not (7.7% vs. 50.0%) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Our study also showed that biofilm-active antibiotic therapy was associated with lower recurrence rates, particularly in the implant retention group. In contrast, Corrigan et al. found that treatment success did not differ with the use of anti-biofilm agents in FRIs with retained implants [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Although the reason for this discrepancy is unclear, the rates of local antibiotic use between the studies may be a possible explanation. Local antibiotics were used in 58% of the patients in the study by Corrigan et al. but only in 6% of the patients in our study [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Local delivery can achieve high local antibiotic levels even in biofilm-embedded bacteria and minimize systemic toxicity risks [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Recently, Rupp et al. reported that a multidisciplinary treatment approach for FRIs was associated with a higher rate of local antibiotic use, as well as fewer amputations and revision surgeries [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite the association between appropriate ID consultation and longer duration of antibiotic therapy, we could not correlate the latter with improved outcomes. Although the optimal duration of antibiotic treatment for FRIs has not been thoroughly investigated, some authors suggest a 6-week course following implant removal and a 12-week regimen when the implant is retained [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In a previous study of 139 FRI cases, no significant difference was observed in treatment failure rates based on the total duration of antibiotic therapy: 3.8% (\u0026lt;\u0026thinsp;6 weeks), 20.0% (6\u0026ndash;9 weeks), and 11.8% (\u0026gt;\u0026thinsp;9 weeks) [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. On the other hand, a small case series indicated that adequate surgery and local antibiotics may reduce the duration of systemic antibiotic use in FRIs [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] and PJIs [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. The ongoing SOLARIO (Short or Long Antibiotic Regimens in Orthopaedics) randomized controlled trial aims to clarify this issue [29]. Further studies are required to determine the optimal duration of antibiotic treatment of FRIs.\u003c/p\u003e \u003cp\u003eThis study has certain limitations. First, the retrospective nature and single-center design may limit the generalizability of our findings to other settings with diverse patient populations, healthcare practices, and microbiological compositions. Second, the effect of anti-biofilm agents on improved outcomes might have been overestimated in our setting, as local antibiotic use was rare and the total duration of antibiotic therapy was relatively shorter than those in previous studies [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Third, the relatively small sample size compromised the statistical power of the study, potentially hindering the detection of differences within the early, delayed, and late infection subgroups.\u003c/p\u003e \u003cp\u003eIn conclusion, consistent involvement of ID specialists in FRI management was associated with higher rates of biofilm-active antibiotic use and prolonged antibiotic therapy. Biofilm-active antibiotics, when administered under the guidance of ID specialists, may contribute to improved outcomes in patients with FRIs. These observations suggest that ID specialists play a crucial role in optimizing antibiotic therapies for FRIs, potentially leading to more targeted and effective treatment strategies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding sources\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. RS-2023-00246999).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the Institutional Review Board of Kyung Hee University Hospital (IRB number: 2023-11-060).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate and publish\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Institutional Review Board of Kyung Hee University Hospital waived the need of obtaining informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eD. Y. K., and K.-H. P. contributed to the conception and design of the study. D. Y. K., K. -C. K., and K.-H. P. collected the data. D. Y. K., K. -C. K., and K.-H. P. analyzed and interpreted the data. D. Y. K., and K.-H. P. drafted the manuscript. C. H. P., J.-H. B., B. O. J., K. H. R., G. K., Y. -M. L. and M. S. L, critically reviewed the manuscript. All authors read and approved the final version of the manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eTrampuz, A. \u0026amp; Zimmerli, W. Diagnosis and treatment of infections associated with fracture-fixation devices. \u003cem\u003eInjury\u003c/em\u003e \u003cb\u003e37\u003c/b\u003e (Suppl 2), S59\u0026ndash;66 (2006).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCourt-Brown, C. M. \u0026amp; McQueen, M. M. Global Forum: Fractures in the Elderly. \u003cem\u003eJ. Bone Joint Surg. Am.\u003c/em\u003e \u003cb\u003e98\u003c/b\u003e (9), e36 (2016).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFang, C. et al. Infection after fracture osteosynthesis - Part I. \u003cem\u003eJ. Orthop. Surg. (Hong Kong)\u003c/em\u003e. \u003cb\u003e25\u003c/b\u003e (1), 2309499017692712 (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMetsemakers, W. J. et al. Infection after fracture fixation: Current surgical and microbiological concepts. \u003cem\u003eInjury\u003c/em\u003e \u003cb\u003e49\u003c/b\u003e (3), 511\u0026ndash;522 (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDepypere, M. et al. Pathogenesis and management of fracture-related infection. \u003cem\u003eClin. Microbiol. Infect.\u003c/em\u003e \u003cb\u003e26\u003c/b\u003e (5), 572\u0026ndash;578 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMetsemakers, W. J. et al. General treatment principles for fracture-related infection: recommendations from an international expert group. \u003cem\u003eArch. Orthop. Trauma. Surg.\u003c/em\u003e \u003cb\u003e140\u003c/b\u003e (8), 1013\u0026ndash;1027 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIliadis, A. D. et al. Current concepts in the prevention, diagnosis and treatment of fracture-related infection (FRI). \u003cem\u003eEur. J. Orthop. Surg. Traumatol.\u003c/em\u003e \u003cb\u003e31\u003c/b\u003e (5), 957\u0026ndash;966 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMetsemakers, W. J. et al. Fracture-related infection: A consensus on definition from an international expert group. \u003cem\u003eInjury\u003c/em\u003e \u003cb\u003e49\u003c/b\u003e (3), 505\u0026ndash;510 (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePulcini, C., Botelho-Nevers, E., Dyar, O. J. \u0026amp; Harbarth, S. The impact of infectious disease specialists on antibiotic prescribing in hospitals. \u003cem\u003eClin. Microbiol. Infect.\u003c/em\u003e \u003cb\u003e20\u003c/b\u003e (10), 963\u0026ndash;972 (2014).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWillenegger, H. \u0026amp; Roth, B. [Treatment tactics and late results in early infection following osteosynthesis]. \u003cem\u003eUnfallchirurgie\u003c/em\u003e \u003cb\u003e12\u003c/b\u003e (5), 241\u0026ndash;246 (1986).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKuehl, R. et al. Time-dependent differences in management and microbiology of orthopaedic internal fixation-associated infections: an observational prospective study with 229 patients. \u003cem\u003eClin. Microbiol. Infect.\u003c/em\u003e \u003cb\u003e25\u003c/b\u003e (1), 76\u0026ndash;81 (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSundararajan, V. et al. New ICD-10 version of the Charlson comorbidity index predicted in-hospital mortality. \u003cem\u003eJ. Clin. Epidemiol.\u003c/em\u003e \u003cb\u003e57\u003c/b\u003e (12), 1288\u0026ndash;1294 (2004).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCharlson, M. E., Pompei, P., Ales, K. L. \u0026amp; MacKenzie, C. R. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. \u003cem\u003eJ. Chronic Dis.\u003c/em\u003e \u003cb\u003e40\u003c/b\u003e (5), 373\u0026ndash;383 (1987).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWalenkamp, G. H., Kleijn, L. L. \u0026amp; de Leeuw, M. Osteomyelitis treated with gentamicin-PMMA beads: 100 patients followed for 1\u0026ndash;12 years. \u003cem\u003eActa Orthop. Scand.\u003c/em\u003e \u003cb\u003e69\u003c/b\u003e (5), 518\u0026ndash;522 (1998).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMetsemakers, W. J. et al. Evidence-Based Recommendations for Local Antimicrobial Strategies and Dead Space Management in Fracture-Related Infection. \u003cem\u003eJ. Orthop. Trauma.\u003c/em\u003e \u003cb\u003e34\u003c/b\u003e (1), 18\u0026ndash;29 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDepypere, M. et al. Recommendations for Systemic Antimicrobial Therapy in Fracture-Related Infection: A Consensus From an International Expert Group. \u003cem\u003eJ. Orthop. Trauma.\u003c/em\u003e \u003cb\u003e34\u003c/b\u003e (1), 30\u0026ndash;41 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLobati, F., Herndon, B. \u0026amp; Bamberger, D. Osteomyelitis: etiology, diagnosis, treatment and outcome in a public versus a private institution. \u003cem\u003eInfection\u003c/em\u003e \u003cb\u003e29\u003c/b\u003e (6), 333\u0026ndash;336 (2001).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZimmerli, W., Widmer, A. F., Blatter, M., Frei, R. \u0026amp; Ochsner, P. E. Role of rifampin for treatment of orthopedic implant-related staphylococcal infections: a randomized controlled trial. Foreign-Body Infection (FBI) Study Group. \u003cem\u003eJAMA\u003c/em\u003e \u003cb\u003e279\u003c/b\u003e (19), 1537\u0026ndash;1541 (1998).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBeldman, M. et al. If, When, and How to Use Rifampin in Acute Staphylococcal Periprosthetic Joint Infections, a Multicentre Observational Study. \u003cem\u003eClin. Infect. Dis.\u003c/em\u003e \u003cb\u003e73\u003c/b\u003e (9), 1634\u0026ndash;1641 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAboltins, C. A. et al. Gram-negative prosthetic joint infection treated with debridement, prosthesis retention and antibiotic regimens including a fluoroquinolone. \u003cem\u003eClin. Microbiol. Infect.\u003c/em\u003e \u003cb\u003e17\u003c/b\u003e (6), 862\u0026ndash;867 (2011).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLora-Tamayo, J. et al. A large multicenter study of methicillin-susceptible and methicillin-resistant Staphylococcus aureus prosthetic joint infections managed with implant retention. \u003cem\u003eClin. Infect. Dis.\u003c/em\u003e \u003cb\u003e56\u003c/b\u003e (2), 182\u0026ndash;194 (2013).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCorrigan, R., Sliepen, J., Rentenaar, R. J., Hietbrink, F. I. J. \u0026amp; Atkins, F. The effect of guideline-based antimicrobial therapy on the outcome of fracture-related infections (EAT FRI Study). \u003cem\u003eJ. Infect.\u003c/em\u003e \u003cb\u003e86\u003c/b\u003e (3), 227\u0026ndash;232 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eter Boo, G. J., Grijpma, D. W., Moriarty, T. F., Richards, R. G. \u0026amp; Eglin, D. Antimicrobial delivery systems for local infection prophylaxis in orthopedic- and trauma surgery. \u003cem\u003eBiomaterials\u003c/em\u003e \u003cb\u003e52\u003c/b\u003e, 113\u0026ndash;125 (2015).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRupp, M. et al. Multidisciplinary Treatment of Fracture-Related Infection Has a Positive Impact on Clinical Outcome-A Retrospective Case Control Study at a Tertiary Referral Center. \u003cem\u003eAntibiot. (Basel)\u003c/em\u003e ;\u003cb\u003e12\u003c/b\u003e(2). (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAl-Mayahi, M. et al. Remission rate of implant-related infections following revision surgery after fractures. \u003cem\u003eInt. Orthop.\u003c/em\u003e \u003cb\u003e37\u003c/b\u003e (11), 2253\u0026ndash;2258 (2013).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStockley, I., Mockford, B. J., Hoad-Reddick, A. \u0026amp; Norman, P. The use of two-stage exchange arthroplasty with depot antibiotics in the absence of long-term antibiotic therapy in infected total hip replacement. \u003cem\u003eJ. Bone Joint Surg. Br.\u003c/em\u003e \u003cb\u003e90\u003c/b\u003e (2), 145\u0026ndash;148 (2008).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNelson, C. L. et al. A comparison of gentamicin-impregnated polymethylmethacrylate bead implantation to conventional parenteral antibiotic therapy in infected total hip and knee arthroplasty. \u003cem\u003eClin. Orthop. Relat. Res.\u003c/em\u003e (295):96\u0026ndash;101. (1993).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"biofilm-active agent, duration of antibiotic therapy, fixation, fracture-related infections, implant failure","lastPublishedDoi":"10.21203/rs.3.rs-6223447/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6223447/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eThe management of fracture-related infections (FRIs) is complex and requires collaboration among various specialists, including trauma and orthopedic surgeons, infectious disease (ID) specialists, and microbiologists. This study aimed to investigate the effects of ID consultations on antibiotic treatment and FRI outcomes.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe conducted a retrospective chart review of data from adult patients with microbiologically diagnosed FRIs at a tertiary care hospital.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eIn total, 123 patients with FRIs were included in the study, with a median follow-up period of 31 months. Sixty-five patients (52.8%) received continuous ID consultations until the completion of their treatment, whereas 58 patients (47.2%) either did not receive any ID consultations or had their consultations terminated prematurely. The patients who received continuous ID consultations were more likely to receive pathogen-directed oral antibiotics (76.9% vs. 36.2%; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), biofilm-active antibiotics (52.3% vs. 8.6%; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and prolonged antibiotic treatment (median, 50 vs. 26 days; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) than those who did not receive such consultations. The multivariate analysis results indicated that Gustilo\u0026ndash;Anderson grade 3 open fractures (adjusted odds ratio [aOR], 3.82; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002), implant retention (aOR, 3.01; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02), and absence or early termination of ID consultations (aOR, 3.17; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.009) were independent predictors of treatment failure. Recurrence was less frequent in the patients who received biofilm-active agents than in those who did not (10.3% vs. 35.7%; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.007).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eIn patients with FRI, appropriate ID consultations were associated with frequent use of biofilm-active antibiotics and improved outcomes.\u003c/p\u003e","manuscriptTitle":"Impact of infectious disease specialist consultations on antibiotic treatment and outcomes of fracture-related infections ","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-15 10:12:07","doi":"10.21203/rs.3.rs-6223447/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-07-23T06:05:10+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-21T16:56:42+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-15T07:48:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"226135376539264180160220374119533605059","date":"2025-07-15T07:28:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"300766308982601199045906274341040007558","date":"2025-07-14T09:46:00+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-12T17:21:51+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"270586474620444023116445308549338758310","date":"2025-05-11T16:12:04+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-05-08T22:54:58+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-07T21:24:12+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-03-24T02:31:48+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-21T06:43:12+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-03-14T03:41:09+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"879179ce-493b-4f90-a102-1f98f866b8ce","owner":[],"postedDate":"May 15th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":48427630,"name":"Health sciences/Diseases/Infectious diseases/Bacterial infection"},{"id":48427631,"name":"Health sciences/Anatomy/Musculoskeletal system/Bone"}],"tags":[],"updatedAt":"2025-11-10T15:59:48+00:00","versionOfRecord":{"articleIdentity":"rs-6223447","link":"https://doi.org/10.1038/s41598-025-22165-1","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-11-03 15:57:17","publishedOnDateReadable":"November 3rd, 2025"},"versionCreatedAt":"2025-05-15 10:12:07","video":"","vorDoi":"10.1038/s41598-025-22165-1","vorDoiUrl":"https://doi.org/10.1038/s41598-025-22165-1","workflowStages":[]},"version":"v1","identity":"rs-6223447","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6223447","identity":"rs-6223447","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}