The effect of under-dosing prophylactic antibiotics in the care of open tibial fractures

Objectives: To determine the frequency and effect of under-dosing prophylactic weight-based antibiotics in patients with open tibial fractures. We hypothesized that patients who did not receive appropriate weight-based dosing of prophylactic antibiotics would have higher rates of infection. Design: Retrospective cohort study. Setting: Level 1 Trauma Center. Patients/Participants: Patients 18 years of age or older with high-grade (Gustilo-Anderson type IIIA or IIIB) open extraarticular tibial fractures over a 5-year period. Main Outcome: The primary outcome was deep infection within one year of initial injury. Appropriate weight-based dosing of cefazolin was defined as: At least 1 g for patients \u3c80 kg, 2 g for patients between 80 and 120 kg, and 3 g for patients \u3e120 kg. Results: Sixty-three patients met the inclusion criteria; 21 (33%) were under-dosed with cefazolin at the time of initial presentation. Among the 20 patients who subsequently developed deep infection, only 55% were appropriately dosed with cefazolin; of the patients who did not develop deep infection, 72% were appropriately dosed with cefazolin (P = 0.18). Univariate analysis revealed that hypertension was associated with infection (P = 0.049). Multivariable logistic regression analysis of infection due to all organisms did not reveal a statistically significant reduction in the odds of infection with appropriate weight-based dosing of cefazolin [Odds ratio = 0.42 (95% confidence interval, 0.12-1.48), P = 0.177]. Five of 7 (71%) of the gram positive, non-methicillin-resistant Staphylococcus aureus, infections occurred in patients who were under-dosed with cefazolin. Five (23.8%) of 21 patients who were under-dosed with cefazolin had gram-positive, non-methicillin-resistant S. aureus infections, compared to 2 (4.8%) of 42 patients who were appropriately dosed (P = 0.036). Conclusions: Under-dosing of weight-based antibiotics in the treatment of open fractures is common. Appropriate weight-based dosing of cefazolin for prophylaxis in high-grade open tibial fractures reduces the frequency of infection due to cefazolin-sensitive organisms. Interestingly, organisms not susceptible to cefazolin were responsible for the majority of infections. The effect of under-dosing of cefazolin and other weight-based antibiotics deserves further investigation in larger studies

PREVENTion of CLots in Orthopaedic Trauma (PREVENT CLOT): a randomised pragmatic trial protocol comparing aspirin versus low-molecular-weight heparin for blood clot prevention in orthopaedic trauma patients

Introduction Patients who sustain orthopaedic trauma are at an increased risk of venous thromboembolism (VTE), including fatal pulmonary embolism (PE). Current guidelines recommend low-molecular-weight heparin (LMWH) for VTE prophylaxis in orthopaedic trauma patients. However, emerging literature in total joint arthroplasty patients suggests the potential clinical benefits of VTE prophylaxis with aspirin. The primary aim of this trial is to compare aspirin with LMWH as a thromboprophylaxis in fracture patients.Methods and analysis PREVENT CLOT is a multicentre, randomised, pragmatic trial that aims to enrol 12 200 adult patients admitted to 1 of 21 participating centres with an operative extremity fracture, or any pelvis or acetabular fracture. The primary outcome is all-cause mortality. We will evaluate non-inferiority by testing whether the intention-to-treat difference in the probability of dying within 90 days of randomisation between aspirin and LMWH is less than our non-inferiority margin of 0.75%. Secondary efficacy outcomes include cause-specific mortality, non-fatal PE and deep vein thrombosis. Safety outcomes include bleeding complications, wound complications and deep surgical site infections.Ethics and dissemination The PREVENT CLOT trial has been approved by the ethics board at the coordinating centre (Johns Hopkins Bloomberg School of Public Health) and all participating sites. Recruitment began in April 2017 and will continue through 2021. As both study medications are currently in clinical use for VTE prophylaxis for orthopaedic trauma patients, the findings of this trial can be easily adopted into clinical practice. The results of this large, patient-centred pragmatic trial will help guide treatment choices to prevent VTE in fracture patients.Trial registration number NCT02984384