Original Investigation 

Surgery

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

Curtis D. Collins, Eric Hartsfield, Robert K. Cleary, et al

JAMA Netw Open 2026;9;(4):e266708. doi:10.1001/jamanetworkopen.2026.6708

Key Points

Question  Are surgical prophylaxis regimens containing β-lactam antibiotics associated with lower surgical site infections (SSIs) compared with non–β-lactam alternative regimens in patients undergoing colorectal operations when considering antibiotic timing and dose optimization?

Findings  In this cohort study including 20 140 procedures in adult patients receiving β-lactam and non–β-lactam alternative prophylaxis for elective colorectal surgery, the use of β-lactam prophylaxis regimens was associated with increased guideline-concordant prophylaxis dosing and timing and reduced SSIs.

Meaning  This study suggests that, regardless of differences in guideline-concordant dosing and timing, β-lactam surgical prophylaxis is associated with lower risk of SSIs compared with those who receive non–β-lactam alternative regimens.

Abstract

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.