Association between generation of cephalosporins and surgical site infection in open fractures: a prospective cohort study

Background: The use of cephalosporins for surgical site infection (SSI) prevention has become a clinical routine, however, high-level evidence regarding the optimal generation for open fractures is currently limited. This study aims to investigate the association between the generation of cephalosporins and SSI risk in open fractures. Methods: This prospective cohort study used data from the Surgical Site Infection in Orthopedic Surgery (SSIOS), a prospectively maintained database, conducted at a tertiary orthopedic university hospital from October 2014 to December 2020. The primary outcome was occurrence of SSI within 1 year after operation, and its association with the generation of cephalosporins was examined using multivariable logistic regressions and generalized estimating equations. Generalized additive models were used to calculate the relative contribution of potential factors likely influencing SSI. Results: A total of 3582 eligible patients, 74.6% males, with a mean age of 43.7 ± 14.1 years, were included. First-, second-, and third-generation cephalosporins were used in 1957 (54.6%), 1219 (34.0%), and 406 (11.3%) patients. Compared to first-generation cephalosporins, the use of second-generation cephalosporins was significantly associated with a higher risk of SSI (absolute risk difference [ARD] = 3.70%; 95% CI, 1.90%–5.51%; adjusted OR [aOR] = 1.604; 95% CI, 1.212–2.124), whereas third-generation cephalosporins were not (ARD = 1.02%; 95% CI, −1.78% to 3.82%; aOR = 1.234; 95% CI, 0.790–1.880). Among the 28 potential factors considered, the generation of cephalosporins was ranked 9th in terms of its impact on the risk of SSI. Conclusion: Perioperative use of higher-generation cephalosporins was not associated with a reduction in postoperative surgical site infections in open fractures. Our study supports existing guidelines that recommend the use of first-generation cephalosporins as the preferred agents for preventing SSIs in open fractures.