Cefazolin vs. alternative beta-lactams for prophylaxis in lower extremity fracture surgery: A target trial emulation

Abstract

Background

Cefazolin is the primary antibiotic for surgical prophylaxis in orthopedic procedures. The cessation of cefazolin supply in approximately 60 % of Japanese hospitals from 2019 to 2020 provided an opportunity to evaluate the effectiveness of alternative beta-lactams for preventing surgical site infection (SSI). Given the global potential for antibiotics shortages, confirming the effectiveness of alternative beta-lactams is critical.

Purpose

This study aims to evaluate the differences in risk of reoperation for SSI between cefazolin and alternative beta-lactams in patients undergoing lower extremity fracture surgeries.

Methods

We emulated a target trial to compare the effectiveness of cefazolin with alternative beta-lactams—specifically broad-spectrum penicillins and cephalosporins—in preventing SSI using a Japanese hospital administrative database provided by JMDC Inc. We included patients undergoing initial open reduction and internal fixation for closed lower extremity fractures between March 1, 2019, and February 29, 2020. The outcome was reoperation for SSI within 30 days after surgery. Risks were estimated using pooled logistic regression with adjustment for confounders via inverse probability weighting. Sensitivity analyses extended the follow-up period to 90 and 365 days.

Results

Of the 16,602 patients analyzed, 35 patients (0.30 %) in the cefazolin group (11,538 patients) and 16 patients (0.32 %) in the alternative beta-lactam group (5,064 patients) underwent reoperation for SSI within 30 days. The estimated 30-day risk was 0.31 % in the cefazolin group and 0.37 % in the alternative beta-lactam group, resulting in a risk difference of −0.06 % (95 % confidence interval [CI], −0.33 to 0.14) and a risk ratio of 0.82 (95 % CI, 0.50 to 1.52). In sensitivity analyses, the estimated 90-day risk was 0.67 % in the cefazolin group and 0.57 % in the alternative beta-lactam group, with a risk difference of 0.10 % (95 % CI, −0.15 to 0.32) and a risk ratio of 1.19 (95 % CI, 0.80 to 1.62). The 365-day risk was 1.02 % and 0.90 %, respectively, with a risk difference of 0.12 % (95 % CI, −0.29 to 0.39) and a risk ratio of 1.13 (95 % CI, 0.78 to 1.51).

Conclusions

In surgeries for lower extremity fractures, substituting cefazolin with alternative beta-lactams did not result in substantial differences in the risk of reoperation for SSI.