β-Lactam vs Non–β-Lactam Antimicrobial Prophylaxis and Surgical Site Infection

Importanceβ-lactam–based surgical antimicrobial prophylaxis (SAP) is the standard for most surgical procedures. Alternatively, and mostly due to allergies, non–β-lactam–based prophylaxis is used. The association between the use of non–β-lactam SAP and an increased risk of surgical site infection (SSI) rate has not yet been conclusively described. ObjectiveTo assess whether non–β-lactam vs β-lactam prophylaxis is associated with the occurrence of SSI. Design, Setting, and ParticipantsThis cohort study was based on the Swissnoso SSI surveillance system of 175 hospitals, including adult patients who underwent a major surgical procedure with SAP administration within 120 minutes prior to incision and postdischarge follow-up from January 2009 to December 2020. Patients with wound contamination class IV were excluded. Data analysis was conducted from July to December 2024. Exposuresβ-Lactam SAP vs non–β-lactam SAP. Main Outcomes and MeasuresThe main outcome was occurrence of SSI, according to Centers for Disease Control and Prevention definitions. Mixed-effects logistic regression models were used to adjust for institutional, patient, and perioperative confounding factors. ResultsOf 538 976 surveilled patients, 348 885 (196 411 [56.3%] female; median [IQR] age, 63.2 [47.0-73.3] years) fulfilled eligibility criteria. β-Lactam SAP was administered in 342 936 patients (98.3%) and non–β-lactam SAP in 5949 patients (1.7%). SSI was diagnosed in 9507 patients (2.8%) exposed to β-lactam SAP vs 364 patients (6.1%) who received non–β-lactam SAP (P < .001). Non–β-lactam SAP was significantly associated with a higher SSI rate (adjusted odds ratio [aOR], 1.78; 95% CI, 1.59-1.99; P < .001) compared with β-lactam SAP. A higher SSI rate for non–β-lactam SAP was found across all procedure types. Secondary analyses found a higher risk of SSI for ciprofloxacin (aOR, 1.57; 95% CI, 1.33-1.87; P < .001), vancomycin (aOR, 1.38; 95% CI, 1.03-1.86; P = .04), and clindamycin (aOR, 2.12; 95% CI, 1.82-2.47; P < .001) compared with β-lactam SAP. Conclusions and RelevanceIn this large cohort study, administration of non–β-lactam SAP was associated with 1.8-fold higher odds of SSI. These findings suggest that non–β-lactam SAP should be avoided whenever possible. A careful evaluation of patients with reported β-lactam allergy should be performed before administering a second-choice antibiotic.