Original Investigation 

Non–β-Lactam Antibiotic Use, β-Lactam Allergy, and Surgical Site Infections

Prateek Agarwal, Rohit Prem Kumar, Louise-Marie Oleksiuk, et al

JAMA Surg 2025;160;(11):1260-1267

doi:10.1001/jamasurg.2025.3789

Key Points

Question  Is the use of β-lactam antibiotics (eg, cephalosporins, penicillins) for surgical prophylaxis associated with fewer surgical site infections (SSIs) across surgical specialties?

Findings  In this cohort study including a database of 49 279 procedures, the use of non–β-lactam antibiotics was associated with a higher incidence of SSI. When controlling for covariates and β-lactam allergy status, non–β-lactam antibiotic use was significantly associated with SSI.

Meaning  This study found that the use of β-lactam antibiotics for surgical prophylaxis was associated with lower SSI incidence compared with non–β-lactams.

Abstract

Importance  Surgical site infections (SSIs) pose significant health and economic burdens. β-lactams are the recommended prophylactic antibiotics for most surgical procedures; however, the association of non–β-lactam antibiotics with SSI incidence is controversial.

Objective  To evaluate the association between reported β-lactam allergy status, β-lactam antibiotics, and SSIs across various surgical specialties.

Design, Setting, and Participants  This was a retrospective cohort study of a prospectively recorded database. The setting was a quaternary health center. Included in the study were patients who underwent surgery from January 2021 to February 2024.

Exposures  Study exposures included antibiotic choice and reported β-lactam allergy, with covariates including demographics, comorbidities, and procedure details.

Main Outcomes and Measures  The primary study outcome was 30- to 90-day SSI incidence.

Results  The study included 49 279 procedures across 10 specialties, with a total of 41 100 patients (mean [SD] age, 61.0 [15.9] years; range, 13-103 years; 21 237 male [51.7%]). Procedures with non–β-lactam antibiotic use had a higher incidence of SSI than procedures with β-lactam antibiotic use (2.2% vs 1.3%; risk ratio [RR], 1.69; 95% CI, 1.28-2.01; P < .001). Procedures in patients with reported β-lactam allergy had a higher incidence of SSI (1.8% vs 1.3%; RR, 1.38; 95% CI, 1.15-1.64; P = .003). These associations were present in logistic regression as well. However, on controlling for covariates and β-lactam allergy, non–β-lactam antibiotic use remained significantly associated with higher SSI incidence (odds ratio [OR], 1.33; 95% CI, 1.00-1.74; P = .04), whereas the association between β-lactam allergy and SSI incidence became nonsignificant (OR, 1.21; 95% CI, 0.97-1.49; P = .09). In subspecialty analysis, only orthopedic surgery retained a significant association between non–β-lactam use and increased SSI (OR, 3.01; 95% CI, 1.41-6.01; P = .003).

Conclusions and Relevance  This cohort study found that β-lactam prophylaxis was associated with significantly lower SSI rates than non–β-lactam agents, and a reported β-lactam allergy did not independently predict infection risk. Implementation of an allergy-focused stewardship guideline was associated with a marked reduction in non–β-lactam use, underscoring the importance of precise allergy assessment to avoid unnecessary alternative prophylaxis.