β-Lactam vs Non–β-Lactam Prophylaxis in Elective Colorectal Surgery

Importance: Previous studies found reduced surgical site infections (SSIs) with β-lactam surgical infection prophylaxis compared with non-β-lactam alternatives; however, variations in timing and dosing have been reported. Whether guideline-concordant preoperative antibiotic dosing or timing are associated with reported SSI differences between regimens is unclear. Objective: To evaluate the incidence of SSIs between patients receiving β-lactam and non-β-lactam alternative prophylaxis, while controlling guideline-concordant dosing and timing. Design, Setting, and Participants: This multicenter retrospective cohort study used data from a validated regional data registry. Adult patients (>18 years) receiving β-lactam and non-β-lactam alternative prophylaxis for elective colorectal surgery between July 2012 and June 2021 were included. Analyses were performed at multiple intervals between March 2022 and January 2026. Exposures: Surgical prophylaxis regimens with β-lactam or non-β-lactam alternative prophylaxis. Receipt of guideline-concordant prophylaxis dose and timing were variables of interest, defined using international guideline recommendations. Main Outcomes and Measures: The primary outcome was 30-day SSI. Modified Poisson regression with robust (sandwich) variance estimators was used to estimate adjusted risk ratios (ARRs) for SSI comparing β-lactam with non-β-lactam alternative prophylaxis, adjusting for guideline-concordant dosing, timing, and other covariates; 1:1 propensity score matching was performed as a sensitivity analysis. Results: Among 20 140 procedures (female, 10 423 [51.8%]; male, 9717 [48.2%]; mean [SD] age, 62.0 [13.8] years), 18 098 (89.9%) received β-lactam prophylaxis and 2042 (10.1%) received non-β-lactam alternative prophylaxis. Baseline characteristics differed between groups. Patients in the β-lactam cohort more commonly received guideline-concordant antibiotic dosing (15 124 [83.6%] vs 1084 [53.1%]; P < .001), guideline-concordant timing (16 946 [93.6%] vs 1707 [83.6%]; P < .001), or combined guideline-concordant dose and timing (14 216 [78.6%] vs 751 [36.8%]; P < .001), and had fewer SSIs (1114 [6.2%] vs 172 [8.4%]; P < .001). After adjusting for confounders, β-lactam prophylaxis was associated with a lower risk of SSIs (ARR, 0.74; 95% CI, 0.63-0.87; P < .001). Neither guideline-concordant dosing (ARR, 1.04; 95% CI, 0.91-1.20; P = .54) nor timing (ARR, 1.13; 95% CI, 0.92-1.38; P = .25) were associated with SSI risk. Conclusions and Relevance: In this cohort study of elective colorectal surgery procedures, β-lactam surgical prophylaxis was associated with significantly lower SSI risk compared with non-β-lactam alternatives. Differences in guideline-concordant dosing and timing between cohorts were not associated with SSI risk in adjusted analyses.