No abstract

Despite a lack of consensus guidelines, local antibiotic administration for prophylaxis of surgical site infections is used during many surgical procedures. The rationale behind this practice is to provide high antibiotic concentrations at the site of surgery while minimizing systemic exposure and adverse effects. Local antibiotic administration for surgical site prophylaxis has inherent limitations in that antibiotics are applied after the incision is made, rather than the current standard for surgical site prophylaxis that recommends providing adequate antibiotic concentrations at the site before the incision. The efficacy and safety of local application of antibiotics for surgical site prophylaxis have been assessed in different types of surgery with a variety of antibiotic agents and methods of application. We identified 22 prospective, randomized, controlled trials that evaluated local application of antibiotics for surgical site prophylaxis. These trials were subsequently divided and analyzed based on the type of surgical procedure: dermatologic, orthopedic, abdominal, colorectal, and cardiothoracic. Methods of local application analyzed included irrigations, powders, ointments, pastes, beads, sponges, and fleeces. Overall, there is a significant lack of level I evidence supporting this practice for any of the surgical genres evaluated. In addition, the literature spans several decades, and changes in surgical procedures, systemic antibiotic prophylaxis, and microbial flora make conclusions difficult to determine. Based on available data, the efficacy of local antibiotic administration for the prophylaxis of surgical site infections remains uncertain, and recommendations supporting this practice for surgical site prophylaxis cannot be made.

BACKGROUND There is a known drug interaction (DI) between xanthine oxidase (XO) inhibitors and the thiopurine immunosuppressants, azathioprine (AZA) and mercaptopurine (6-MP). Xanthine oxidase inhibition increases concentrations of AZA and 6-MP active metabolites, possibly resulting in myelosuppression. When allopurinol is used with AZA or 6-MP, dose reduction of AZA or 6-MP is recommended. Febuxostat is a newer XO inhibitor approved for the treatment of gout. OBJECTIVE To determine the clinical impact of the febuxostat-thiopurine DI. DESIGN AND SETTING Case series derived from the U.S. Food and Drug Administration Adverse EventReporting System (FAERS) and published medical literature. PATIENTS Nineteen patients who received concomitant febuxostat and either AZA or 6-MP. MEASUREMENTS Laboratory and clinical data. RESULTS Nineteen cases reporting myelosuppressive events were identified in patients receiving febuxostat with AZA or 6-MP. Eighteen cases were treated with the combination of AZA and febuxostat. A median of 1.6 months elapsed from initiation of the drug combination until discovery of the event. Sixteen cases required hospitalization; 15 reported administration of blood products. Thirteen cases reported resolution of the event with discontinuation of both drugs, two reported discontinuation of the thiopurine only, and one reported discontinuation of febuxostat only. LIMITATIONS Thiopurine monotherapy may cause myelosuppression. Complications of immunosuppression that may contribute to the real-world morbidity and mortality associated with the febuxostatthiopurine DI were not examined. Finally, FAERS data are limited by the voluntary nature of reporting. CONCLUSION Current febuxostat labeling contraindicates concomitant administration of febuxostat with either AZA or 6-MP. This case series demonstrates that the DI can result in clinically significant adverse events and is supportive of current febuxostat labeling.

Topical tranexamic acid may have a role in the treatment of anterior epistaxis in select ED patients, though additional studies are needed to confirm its role in treatment algorithms.