Does Topical Vancomycin Powder Use in Fracture Surgery Change Bacteriology and Antibiotic Susceptibilities? An Analysis of the VANCO Trial.

OBJECTIVE: To determine whether intrawound vancomycin changes the bacteriology of surgical site infection pathogens and investigate the emergence of antibiotic-resistant pathogens. DESIGN: Secondary analysis of phase III, prospective, randomized clinical trial. SETTING: Thirty-six US trauma centers. PATIENT SELECTION CRITERIA: Patients who became infected after fixation of tibial plateau or pilon fracture. OUTCOME MEASURES AND COMPARISONS: Pathogen types and bacterial susceptibilities as determined from routine clinical culture in the operating room. RESULTS: Seventy-four patients were studied who were 67.5% male with a mean age of 48.6 years. A lower proportion of gram-positive cocci was observed in the vancomycin powder compared with the standard-of-care group (3.7% vs. 8.0%, P = 0.01). Methicillin-resistant Staphylococcus aureus infection incidence was comparable in both the vancomycin powder and the standard-of-care groups, but rates of methicillin-susceptible S. aureus infections were lower in the treatment group (1.4% vs. 4.8%, P = 0.01). The incidence of coagulase-negative Staphylococci and gram-negative rod infections were similar in both groups. There was no significant difference in susceptibilities between groups in rates of vancomycin-resistant enterococcus. CONCLUSIONS: Topical vancomycin powder decreases the likelihood of gram-positive infections consistent with the biologic activity of vancomycin. Fewer methicillin-susceptible S. aureus and coagulase-negative Staphylococci infections were observed in the group treated with vancomycin powder. An effect of vancomycin powder on methicillin-resistant S. aureus infection risk was not detected given the low incidence in both the intrawound vancomycin and the standard-of-care groups. There was no emergence of gram-negative rod infections or increased resistance patterns observed. Use of topical vancomycin powder does not seem to produce infections in these patients with greater antibiotic resistance than would have occurred without its use. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Skin Antisepsis before Surgical Fixation of Extremity Fractures.

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

Predicting Which Species of Bacteria Will Cause an Infection After Fracture Surgery.

The aim of this study was to develop and validate risk prediction models for deep surgical site infection (SSI) caused by specific bacterial pathogens after fracture fixation. A retrospective case-control study was conducted at a level I trauma center. Fifteen candidate predictors of the bacterial pathogens in deep SSI were evaluated to develop models of bacterial risk. The study included 441 patients with orthopedic trauma with deep SSI after fracture fixation and 576 control patients. The main outcome measurement was deep SSI cultures positive for methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant S aureus (MRSA), gram-negative rods (GNRs), anaerobes, or polymicrobial infection within 1 year of injury. Prognostic models were developed for five bacterial pathogen outcomes. Mean area under the curve ranged from 0.70 (GNRs) to 0.74 (polymicrobial). Strong predictors of MRSA were American Society of Anesthesiologists (ASA) classification of III or greater (odds ratio [OR], 3.4; 95% CI, 1.6-8.0) and time to fixation greater than 7 days (OR, 3.4; 95% CI, 1.9-5.9). Gustilo type III fracture was the strongest predictor of MSSA (OR, 2.5; 95% CI, 1.6-3.9) and GNRs (OR, 3.4; 95% CI, 2.3-5.0). ASA classification of III or greater was the strongest predictor of polymicrobial infection (OR, 5.9; 95% CI, 2.7-15.5) and was associated with increased odds of GNRs (OR, 2.7; 95% CI, 1.5-5.5). Our models predict the risk of MRSA, MSSA, GNR, anaerobe, and polymicrobial infections in patients with fractures. The models might allow for modification of preoperative antibiotic selection based on the particular pathogen posing greatest risk for this patient population. [Orthopedics. 2024;47(1):e19-e25.].

The VANCO Trial Findings Are Generalizable to a North American Trauma Registry.

OBJECTIVES: To estimate the generalizability of treatment effects observed in the VANCO trial to a broader population of patients with tibial plateau or pilon fractures. METHODS: Design and Setting: Clinical trial data from 36 United States trauma centers and Trauma Quality Programs registry data from more than 875 Level I-III trauma centers in the United States and Canada.Patient Selection Criteria: Patients enrolled in the VANCO trial treated with intrawound vancomycin powder from January 2015 to June 2017 and 31,924 VANCO-eligible TQP patients admitted in 2019 with tibial plateau and pilon fractures.Outcome Measure and Comparisons: Deep surgical site infection and gram-positive deep surgical site infection estimated in the TQP sample weighed by the inverse probability of trial participation. RESULTS: The 980 patients in the VANCO trial were highly representative of 31,924 TQP VANCO-eligible patients (Tipton generalizability index 0.96). It was estimated that intrawound vancomycin powder reduced the odds of deep surgical infection by odds ratio (OR) = 0.46 (95% confidence interval [CI] 0.25-0.86) and gram-positive deep surgical infection by OR = 0.39 (95% CI, 0.18-0.84) within the TQP sample of VANCO-eligible patients. For reference, the trial average treatment effects for deep surgical infection and gram-positive deep surgical infection were OR = 0.60 (95% CI, 0.37-0.98) and OR = 0.44 (95% CI, 0.23-0.80), respectively. CONCLUSIONS: This generalizability analysis found that the inferences of the VANCO trial generalize and might even underestimate the effects of intrawound vancomycin powder when observed in a wider population of patients with tibial plateau and pilon fractures. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Local administration of vancomycin powder in orthopaedic fracture surgery: current practice and trends.

Objectives: Surgical site infections in orthopaedic trauma are a significant problem with meaningful patient and health care system-level consequences. Direct application of antibiotics to the surgical field has many potential benefits in reducing surgical site infections. However, to date, the data regarding the local administration of antibiotics have been mixed. This study reports on the variability of prophylactic vancomycin powder use in orthopaedic trauma cases across 28 centers. Methods: Intrawound topical antibiotic powder use was prospectively collected within three multicenter fracture fixation trials. Fracture location, Gustilo classification, recruiting center, and surgeon information were collected. Differences in practice patterns across recruiting center and injury characteristics were tested using chi-square statistic and logistic regression. Additional stratified analyses by recruiting center and individual surgeon were performed. Results: A total of 4941 fractures were treated, and vancomycin powder was used in 1547 patients (31%) overall. Local administration of vancomycin powder was more frequent in open fractures 38.8% (738/1901) compared with closed fractures 26.6% (809/3040) (P < 0.001). However, the severity of the open fracture type did not affect the rate at which vancomycin powder was used (P = 0.11). Vancomycin powder use varied substantially across the clinical sites (P < 0.001). At the surgeon level, 75.0% used vancomycin powder in less than one-quarter of their cases. Conclusions: Prophylactic intrawound vancomycin powder remains controversial with varied support throughout the literature. This study demonstrates wide variability in its use across institutions, fracture types, and surgeons. This study highlights the opportunity for increased practice standardization for infection prophylaxis interventions. Level of Evidence: Prognostic-III.

The Use of Vancomycin Powder in Tibial Plateau Fractures at Lower Risk of Infection.

OBJECTIVE: To determine the effectiveness of vancomycin powder in preventing infection after plate and screw fixation of tibial plateau fractures considered at low risk of infection. DESIGN: Retrospective cohort study. SETTING: Single, Level I trauma center. PATIENTS/PARTICIPANTS: This study included 459 patients with tibial plateau fractures (OTA/AO 41-B/C) who underwent open reduction and internal fixation from 2006 to 2018 and were considered at low risk of infection based on not meeting the "high risk" definition of the VANCO trial. INTERVENTION: Vancomycin powder administration on wound closure at the time of definitive fixation. MAIN OUTCOME MEASUREMENTS: Deep surgical site infection with at least 1 gram-positive bacteria culture. RESULTS: Vancomycin powder administration was associated with reduction in gram-positive infection from 4% to 0% (odds ratio, 0.12; 95% confidence interval, 0.04-0.32; P < 0.01). No significant effect was reported in gram-negative only infections, which were observed in 0.3% in the control group, compared with 0.9% in the intervention group (odds ratio, 2.71; 95% confidence interval, 0.11-69; P = 0.54). Methicillin-resistant Staphylococcus aureus was the most common organism isolated in the control group, growing in 9 of 18 infections (50%). CONCLUSIONS: Among patients with low-risk tibial plateau fractures, vancomycin powder at the time of definitive fixation showed a reduction in the incidence of gram-positive deep surgical site infection. The observed relative effect was relatively larger than that observed in a previous randomized trial on high-risk fractures. These data might support broadening the indication for use of vancomycin powder to include tibial plateau fractures at low risk of infection. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Application of Bayesian Methods to Help Interpret the VANCO Trial Results.

OBJECTIVE: To determine whether a Bayesian analysis changes the results of the VANCO trial. DESIGN: A secondary analysis of a randomized clinical trial using Bayesian methods. SETTING: Thirty-six US trauma centers. PATIENTS: Patients ages 18-80 years with a tibial plateau or pilon fracture deemed high risk of infection and definitively treated with plate and screw fixation. INTERVENTION: Patients were randomly allocated to receive 1000 mg of intrawound vancomycin powder at their definitive fixation or to a control group that received no topical antibiotics. MAIN OUTCOME MEASUREMENTS: A deep surgical site infection requiring operative treatment within 6 months of definitive fixation. Secondary outcomes included gram-positive and gram-negative-only deep surgical site infections. RESULTS: Of the 980 patients randomized, 874 (89%) had at least 140 days of follow-up and were included in this Bayesian analysis. The estimated probability that intrawound vancomycin powder reduces the risk of a deep surgical site infection is >98% [relative risk (RR), 0.66; 95% credible interval (CrI), 0.46-0.98]. There is a >99% chance intrawound vancomycin powder reduces gram-positive infections and an 80% chance the magnitude of this risk reduction exceeds 35% (RR, 0.52; 95% CrI, 0.33-0.84) exists. It is unlikely (44%) that intrawound vancomycin powder prevents gram-negative surgical site infections (RR, 1.06; 95% CrI, 0.48-2.45). CONCLUSIONS: There is a high probability (>98%) that intrawound vancomycin powder reduces deep surgical site infections in patients with tibial plateau or pilon fractures at high risk of infection and even more likely it reduces deep infections with gram-positive pathogens (>99%). LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Does cumulative topical antibiotic powder use increase the risk of drug induced acute kidney injury in fracture patients?

AIMS: There is increasing evidence to support the use of topical antibiotics to prevent surgical site infections. Although previous research suggests a minimal nephrotoxic risk with a single dose of vancomycin powder, fracture patients often require multiple procedures and receive additional doses of topical antibiotics. We aimed to determine if cumulative doses of intrawound vancomycin or tobramycin powder for infection prophylaxis increased the risk of drug-induced acute kidney injury (AKI) among fracture patients. METHODS: This cohort study was a secondary analysis of single-centre Program of Randomized Trials to Evaluate Pre-operative Antiseptic Skin Solutions in Orthopaedic Trauma (PREP-IT) trial data. We included patients with a surgically treated appendicular fracture. The primary outcome was drug-induced AKI. The odds of AKI per gram of vancomycin or tobramycin powder were calculated using Bayesian regression models, which adjusted for measured confounders and accounted for the interactive effects of vancomycin and tobramycin. RESULTS: Of the 782 included patients (mean age 48 years (SD 20); 59% male), 83% (n = 648) received at least one vancomycin dose (cumulative range 1 to 12 g). Overall, 45% of the sample received at least one tobramycin dose (cumulative range 1.2 to 9.6 g). Drug-induced AKI occurred in ten patients (1.2%). No association was found between the cumulative dose of vancomycin and drug-induced AKI (odds ratio (OR) 1.08 (95% credible interval (CrI) 0.52 to 2.14)). Additional doses of tobramycin were associated with a three-fold increase in the adjusted odds of drug-induced AKI (OR 3.66 (95% CrI 1.71 to 8.49)). Specifically, the risk of drug-induced AKI rose substantially after 4.8 g of tobramycin powder (7.5% (95% CrI 1.0 to 35.3)). CONCLUSION: Cumulative doses of vancomycin were not associated with an increased risk of drug-induced AKI among fracture patients. While the risk of drug-induced AKI remains less than 4% with three or fewer 1.2 g tobramycin doses, the estimated risk increases substantially to 8% after four cumulative doses. Level of evidence: Therapeutic Level III Cite this article: Bone Jt Open 2022;3(4):284-290.

Poor Agreement Between Next-Generation DNA Sequencing and Bacterial Cultures in Orthopaedic Trauma Procedures.

BACKGROUND: Next-generation DNA sequencing (NGS) detects bacteria-specific DNA corresponding to the 16S ribosomal RNA gene and can identify bacterial presence with greater accuracy than traditional culture methods. The clinical relevance of these findings is unknown. The purpose of the present study was to compare the results from bacterial culture and NGS in order to characterize the potential use of NGS in orthopaedic trauma patients. METHODS: A prospective cohort study was performed at a single academic, level-I trauma center. Three patient groups were enrolled: (1) patients undergoing surgical treatment of acute closed fractures (presumed to have no bacteria), (2) patients undergoing implant removal at the site of a healed fracture without infection, and (3) patients undergoing a first procedure for the treatment of a fracture nonunion who might or might not have subclinical infection. Surgical site tissue was sent for culture and NGS. The proportions of culture and NGS positivity were compared among the groups. The agreement between culture and NGS results was assessed with use of the Cohen kappa statistic. RESULTS: Bacterial cultures were positive in 9 of 111 surgical sites (110 patients), whereas NGS was positive in 27 of 111 surgical sites (110 patients). Significantly more cases were positive on NGS as compared with culture (24% vs. 8.1%; p = 0.001), primarily in the acute closed fracture group. No difference was found in terms of the percent positivity of NGS when comparing the acute closed fracture, implant removal, and nonunion groups. With respect to bacterial identification, culture and NGS agreed in 73% of cases (κ = 0.051; 95% confidence interval, -0.12 to 0.22) indicating only slight agreement compared with expected chance agreement of 50%. CONCLUSIONS: NGS identified bacterial presence more frequently than culture, but with only slight agreement between culture and NGS. It is possible that the increased frequency of bacterial detection with molecular methods is reflective of biofilm presence on metal or colonization with nonpathogenic bacteria, as culture methods have selection pressure posed by restrictive, artificial growth conditions and there are low metabolic activity and replication rates of bacteria in biofilms. Our data suggest that NGS should not currently substitute for or complement conventional culture in orthopaedic trauma cases with low suspicion of infection. LEVEL OF EVIDENCE: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Are deep infections that present before and after 90 days from orthopaedic trauma different? An analysis of the validity of the recent change in CDC criteria for infections.

BACKGROUND: In 2016, the Centers for Disease Control and Prevention (CDC) changed the time frame for their definition of deep surgical site infection (SSI) from within 1 year to within 90 days of surgery. We hypothesized that a substantial number of infections in patients who have undergone fracture fixation present beyond 90 days and that there are patient or injury factors that can predict who is more likely to present with SSI after 90 days. METHODS: A retrospective review yielded 452 deep SSI after fracture fixation. These patients were divided into two groups-those infected within 90 days of surgery and those infected beyond 90 days . Data were collected on risk factors for infection. Univariate and multiple logistic regression analyses were performed to compare the two groups. A randomly selected control group was used to build infection prediction models for both outcomes. The two outcomes were then modelled against each other to determine whether differences in predictors for early versus late infection exist. RESULTS: Of the 452 infections, 144 occurred beyond 90 days (32% [95% CI, 28%-36%]). No statistically significant patient factors were found in multivariable analysis between the early and late infection groups. The need for flap coverage was the only injury characteristic that differed significantly between groups, with patients in the late infection group more likely to have needed a flap. When modelled against the control group and directly comparing the two models, predictors for early infection include male sex and fractures of the pelvis, acetabulum, or hip, whereas predictors of late infection include hepatitis C and/or human immunodeficiency virus (HIV) and admission to the intensive care unit (ICU). CONCLUSION: Use of the recent CDC definition will underestimate the rate of actual postoperative infections when applied to orthopaedic trauma patients. Hepatitis C and/or HIV and ICU admission are predictors of late infection, whereas male sex and pelvis, acetabulum, or hip fractures are predictors of early infection. Patients who receive flap coverage may be more likely to present with late infection.

Admission Hyperglycemia Is a Risk Factor for Deep Surgical-Site Infection in Orthopaedic Trauma Patients.

OBJECTIVES: To evaluate the association of admission blood glucose ≥200 mg/dL and surgical site infection in orthopaedic trauma surgery. DESIGN: Retrospective, case control study. SETTING: Academic trauma center. PATIENTS: Four hundred sixty-five nondiabetic, noncritically ill orthopaedic trauma patients with an extremity, pelvic, or acetabular fracture and requiring open reduction and internal fixation or intramedullary nailing. INTERVENTION: None. MAIN OUTCOME MEASUREMENTS: Ninety-day deep surgical site infection. RESULTS: Admission blood glucose ≥200 mg/dL was significantly associated with the primary outcome (8/128, 6.3% vs. 35/337, 1.8%; P = 0.01). Multivariable logistic regression modeling demonstrated that admission blood glucose ≥200 mg/dL was a significant risk factor for deep surgical site infections [odds ratio (OR): 4.7, 95% confidence interval (CI) 1.4-15.7], after controlling for male gender (OR: 1.8, 95% CI: 1.1-3.1), prior drug or alcohol abuse (OR: 1.9, 95% CI 0.9-4.0), open fracture (OR: 6.4, 95% CI 3.7-11.0), and fracture region (upper extremity OR: reference; pelvis/hip OR: 3.9, 95% CI 1.6-9.7; femur OR: 2.0, 95% CI 0.88-4.8; tibia/ankle OR: 3.3, 95% CI 1.7-6.2; and foot OR: 2.7, 95% CI 1.2-6.3). CONCLUSIONS: Admission glucose ≥200 mg/dL was a significant independent risk factor for 90-day deep surgical site infections in orthopaedic trauma patients and may serve as an important marker for infection risk. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Risk factors for treatment failure of fracture-related infections.

OBJECTIVE: Infection after fracture fixation is a potentially devastating outcome, and surgical management is frequently unsuccessful at clearing these infections. The purpose of this study is to determine if factors can be identified that are associated with treatment failure after operative management of a deep surgical site infection. METHODS: We retrospectively reviewed the billing system at a Level I trauma center between March 2006 and December 2015. We identified 451 patients treated for deep surgical site infection after fracture fixation at our center. A multivariate regression analysis was then performed to evaluate for factors associated with treatment failure. RESULTS: Mean follow-up was 2.3 years. One hundred fifty-six patients (35%) failed initial surgical management. Risk factors associated with treatment failure included initial culture results positive for polymicrobial organisms (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.0-2.4), removal of implants (OR, 1.9; 95% CI, 1.2-2.9), or Gustilo-Anderson IIIB/IIIC injury (OR, 2.0; 95% CI, 1.1-3.7). Increased body mass index and fulfilling the criteria to have a methicillin-resistant Staphylococcus aureus (MRSA) nasal swab screening showed a trend toward increased risk of failure. CONCLUSION: Treatment failure after deep surgical site infection was relatively common. Three distinct factors (polymicrobial infection, removal of implants, and IIIB/C fracture) were associated with failure to eradicate the infection in the first series of surgeries and antibiotics. These data might help guide clinicians as they counsel patients on the risk of treatment failure and might focus efforts to improve treatment toward patients at higher risk of treatment failure.

Effect of Intrawound Vancomycin Powder in Operatively Treated High-risk Tibia Fractures: A Randomized Clinical Trial.

Importance: Despite the widespread use of systemic antibiotics to prevent infections in surgically treated patients with fracture, high rates of surgical site infection persist. Objective: To examine the effect of intrawound vancomycin powder in reducing deep surgical site infections. Design, Setting, and Participants: This open-label randomized clinical trial enrolled adult patients with an operatively treated tibial plateau or pilon fracture who met the criteria for a high risk of infection from January 1, 2015, through June 30, 2017, with 12 months of follow-up (final follow-up assessments completed in April 2018) at 36 US trauma centers. Interventions: A standard infection prevention protocol with (n = 481) or without (n = 499) 1000 mg of intrawound vancomycin powder. Main Outcomes and Measures: The primary outcome was a deep surgical site infection within 182 days of definitive fracture fixation. A post hoc comparison assessed the treatment effect on gram-positive and gram-negative-only infections. Other secondary outcomes included superficial surgical site infection, nonunion, and wound dehiscence. Results: The analysis included 980 patients (mean [SD] age, 45.7 [13.7] years; 617 [63.0%] male) with 91% of the expected person-time of follow-up for the primary outcome. Within 182 days, deep surgical site infection was observed in 29 of 481 patients in the treatment group and 46 of 499 patients in the control group. The time-to-event estimated probability of deep infection by 182 days was 6.4% in the treatment group and 9.8% in the control group (risk difference, -3.4%; 95% CI, -6.9% to 0.1%; P = .06). A post hoc analysis of the effect of treatment on gram-positive (risk difference, -3.7%; 95% CI, -6.7% to -0.8%; P = .02) and gram-negative-only (risk difference, 0.3%; 95% CI, -1.6% to 2.1%; P = .78) infections found that the effect of vancomycin powder was a result of its reduction in gram-positive infections. Conclusions and Relevance: Among patients with operatively treated tibial articular fractures at a high risk of infection, intrawound vancomycin powder at the time of definitive fracture fixation reduced the risk of a gram-positive deep surgical site infection, consistent with the activity of vancomycin. Trial Registration: ClinicalTrials.gov Identifier: NCT02227446.

Evaluation of Intra-Operative Topical Vancomycin and the Incidence of Acute Kidney Injury.

Background: Intra-operative topical vancomycin (VAN) is a strategy used to prevent surgical site infections (SSI). Although evidence supporting efficacy in SSI prevention is evolving, data describing safety, specifically acute kidney injury (AKI), are limited. The purpose of this study was to determine AKI incidence in patients who received intra-operative topical VAN. Patients and Methods: This is a retrospective study of adult inpatient encounters in which topical VAN was administered intra-operatively as powder/paste, beads, rods/cement/spacers, or unspecified topical route from February to July 2018. Patients were excluded for AKI or renal replacement therapy (RRT) at baseline or ≤2 serum creatinine (SCr) values post-surgery. The primary outcome was AKI incidence after intra-operative topical VAN, defined as increase in SCr ≥50% or 0.5 mg/dL from baseline or RRT initiation. Secondary outcomes included analysis of AKI risk factors and SSI incidence. Acute kidney injury risk factors were analyzed using multivariable logistic regression. Results: Five hundred thirty-four patient encounters met study criteria. Powder/paste were the most common topical VAN formulations (44.8%) with median doses of 2,000 (range, 1,000-26,000) mg. Acute kidney injury incidence was 8.8%. Independent risk factors for AKI were higher Charlson comorbidity index (adjusted odds ratio [aOR], 1.20 [range, 1.06-1.36]), concomitant systemic VAN (aOR, 2.44 [range, 1.29-4.58]), and doubling of total topical VAN dose (aOR, 1.51 [range, 1.13-2.03]). Conclusions: The incidence of AKI with intra-operative topical VAN is comparable to reported rates as systemic VAN. Clinicians may consider total topical VAN dose and concomitant systemic VAN to limit AKI incidence with topical VAN use.

Low Adherence to Recommended Guidelines for Open Fracture Antibiotic Prophylaxis.

BACKGROUND: Prompt administration of antibiotics is a critical component of open fracture treatment. Traditional antibiotic recommendations have been a first-generation cephalosporin for Gustilo Type-I and Type-II open fractures, with the addition of an aminoglycoside for Type-III fractures and penicillin for soil contamination. However, concerns over changing bacterial patterns and the side effects of aminoglycosides have led to interest in other regimens. The purpose of the present study was to describe the adherence to current prophylactic antibiotic guidelines. METHODS: We evaluated the antibiotic-prescribing practices of 24 centers in the U.S. and Canada that were participating in 2 randomized controlled trials of skin-preparation solutions for open fractures. A total of 1,234 patients were evaluated. RESULTS: All patients received antibiotics on the day of admission. The most commonly prescribed antibiotic regimen was cefazolin monotherapy (53.6%). Among patients with Type-I and Type-II fractures, there was 61.1% compliance with cefazolin monotherapy. In contrast, only 17.2% of patients with Type-III fractures received the recommended cefazolin and aminoglycoside therapy, with an additional 6.7% receiving piperacillin/tazobactam. CONCLUSIONS: There is moderate adherence to the traditional antibiotic treatment guidelines for Gustilo Type-I and Type-II fractures and low adherence for Type-III fractures. Given the divergence between current practice patterns and prior recommendations, high-quality studies are needed to determine the most appropriate prophylactic protocol.

Adjuvant antibiotic-loaded bone cement: Concerns with current use and research to make it work.

Antibiotic-loaded bone cement (ALBC) is broadly used to treat orthopaedic infections based on the rationale that high-dose local delivery is essential to eradicate biofilm-associated bacteria. However, ALBC formulations are empirically based on drug susceptibility from routine laboratory testing, which is known to have limited clinical relevance for biofilms. There are also dosing concerns with nonstandardized, surgeon-directed, hand-mixed formulations, which have unknown release kinetics. On the basis of our knowledge of in vivo biofilms, pathogen virulence, safety issues with nonstandardized ALBC formulations, and questions about the cost-effectiveness of ALBC, there is a need to evaluate the evidence for this clinical practice. To this end, thought leaders in the field of musculoskeletal infection (MSKI) met on 1 August 2019 to review and debate published and anecdotal information, which highlighted four major concerns about current ALBC use: (a) substantial lack of level 1 evidence to demonstrate efficacy; (b) ALBC formulations become subtherapeutic following early release, which risks induction of antibiotic resistance, and exacerbated infection from microbial colonization of the carrier; (c) the absence of standardized formulation protocols, and Food and Drug Administration-approved high-dose ALBC products to use following resection in MSKI treatment; and (d) absence of a validated assay to determine the minimum biofilm eradication concentration to predict ALBC efficacy against patient specific micro-organisms. Here, we describe these concerns in detail, and propose areas in need of research.

Topical Vancomycin Powder Decreases the Proportion of Staphylococcus aureus Found in Culture of Surgical Site Infections in Operatively Treated Fractures.

OBJECTIVES: To determine whether patients with operatively treated fractures and surgical site infection after use of topical vancomycin powder have a lower proportion of Staphylococcus aureus infections than patients who did not receive topical vancomycin powder. DESIGN: Retrospective cohort study. SETTING: Level I trauma center. PATIENTS: Treatment group: 10 of 133 patients (145 fractures) with surgical site infections who received intrawound vancomycin powder at the time of wound closure for fracture fixation. Control group: 175 patients who sustained deep surgical site infections during the same period but did not receive vancomycin powder. INTERVENTION: Vancomycin powder or no vancomycin powder. MAIN OUTCOME MEASUREMENT: Proportion of patients' cultures positive for S. aureus. RESULTS: The proportion of cultures positive for S. aureus was significantly lower in patients with surgical site infection who received vancomycin powder than in those who did not receive vancomycin powder (10% [1 of 10 patients in the treatment group] vs. 50% [87 of 175 patients in the control group]; P = 0.02). A trend was observed for a lower proportion of methicillin-resistant S. aureus (0% vs. 23%; P = 0.12). CONCLUSIONS: Vancomycin powder might alter the bacteriology of surgical site infections and decrease the proportion in culture of the most common organism typically present after fracture surgery infection. These findings suggest that the application of vancomycin powder might change the bacteriology of surgical site infections when they occur, regardless of the effect on overall infection rates. Although our bacteriology results are clinically and statistically significant, these findings must be confirmed in larger randomized controlled trials. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Systemic Absorption and Nephrotoxicity Associated With Topical Vancomycin Powder for Fracture Surgery.

OBJECTIVES: To determine whether using topical vancomycin powder in fracture surgery may result in low levels of vancomycin in the serum and not result in nephrotoxicity. DESIGN: Prospective observational at a single site as a substudy of the VANCO trial. SETTING: Single, large urban level I trauma center. PATIENTS/PARTICIPANTS: Fifty-eight patients with tibial plateau and pilon fractures randomized to the treatment arm at the principal investigator's site. INTERVENTION: Topical vancomycin powder (1000 mg) applied directly in the wound over all metal implants at the time of wound closure. MAIN OUTCOME MEASUREMENTS: Serum vancomycin levels at 1 hour and 6-8 hours after surgery. Secondary outcomes included serum creatinine before surgery, a day after surgery, and at 2 weeks postoperatively and complete blood count at 2 weeks postoperatively. RESULTS: Except in 2 patients who also received intravenous vancomycin, none of the study patients had detectable (>5 µg/mL) serum vancomycin levels at 1 hour and 6-8 hours after surgery. One patient with a history of elevation of serum creatinine had a minor increase of serum creatinine but had undetectable vancomycin levels. None of the other patients had a clinically significant increase in creatinine levels. CONCLUSIONS: Despite its relatively widespread usage, little data exist regarding the systemic levels and nephrotoxicity associated with the topical use of vancomycin powder in orthopaedic fracture surgery. These prospective data indicate that there seems to be little clinical concern regarding toxicity associated with systemic absorption of vancomycin powder in this specific clinical application. LEVEL OF EVIDENCE: Therapeutic Level IV. See instructions for authors for a complete description of levels of evidence.

Vancomycin Powder Use in Fractures at High Risk of Surgical Site Infection.

OBJECTIVES: To determine if the use of intrawound vancomycin powder reduces surgical-site infection after open reduction and internal fixation of bicondylar tibial plateau, tibial pilon, and calcaneus fractures. DESIGN: Retrospective analysis. SETTING: Level I trauma center. PATIENTS: All fractures operatively treated from January 2011 to February 2015 were reviewed; 583 high-risk fractures were included, of which 35 received topical vancomycin powder. A previously published prospectively collected cohort of 235 similar high-risk fractures treated at our center from 2007 through 2010 served as a second comparison group. INTERVENTION: Topical vancomycin powder at wound closure. MAIN OUTCOME MEASUREMENTS: Deep surgical-site infection. Analyses used both univariate comparison of all patients and 1:2 matching analysis using both nearest neighbor and propensity-based matching. RESULTS: Compared with a control group of fractures treated during the same time period without vancomycin powder, the infection rate with vancomycin powder was significantly lower [0% (0/35) vs. 10.6% (58/548), P = 0.04]. Compared with our previously published historical infection rate of 13% for these injuries, vancomycin powder was also associated with significantly decreased deep surgical-site infection (0% vs. 13%, P = 0.02). These results agreed with the matched analyses, which also showed lower infection in the vancomycin powder group (0% vs. 11%-16%, P ≤ 0.05). CONCLUSIONS: Vancomycin powder may play a role in lowering surgical-site infection rates after fracture fixation. A larger randomized controlled trial is needed to validate our findings. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.