Research Summary

Can β-Lactam Antibiotics Reduce Surgical Site Infections Across Specialties?

Anthony Calabro, MA

Key Highlights

  • Non–β-lactam antibiotic use was linked to a higher surgical site infection (SSI) rate than β-lactam use (2.2% vs 1.3%).
  • After adjustment, non–β-lactam use remained significantly associated with SSI.
  • β-lactam allergy status alone did not independently predict SSI risk.
  • Orthopedic procedures showed the strongest association between non–β-lactam use and SSI.

In a cohort of more than 40,000 patients undergoing nearly 50,000 surgical procedures, β-lactam antibiotic prophylaxis was associated with fewer surgical site infections (SSIs) than non–β-lactam alternatives. Patients who received non–β-lactam antibiotics had nearly 70% higher infection risk overall (2.2% vs 1.3%; RR, 1.69; P < .001), and this association persisted even after controlling for β-lactam allergy and other covariates. Orthopedic surgeries were particularly affected, with non–β-lactam use tripling the odds of SSI.

Surgical site infections remain a persistent and costly postoperative complication despite advances in infection prevention. In this large retrospective cohort study published in JAMA Surgery, investigators sought to determine whether the choice of perioperative antibiotic, specifically β-lactam versus non–β-lactam agents, affects SSI rates across multiple surgical specialties and whether reported β-lactam allergy contributes independently to infection risk.

The study addresses an important clinical dilemma. Although β-lactam antibiotics, including cephalosporins and penicillins, are recommended for surgical prophylaxis, many patients are labeled as allergic to β-lactams, prompting use of alternative antibiotics. These substitutions are often less effective, more costly, and may contribute to antimicrobial resistance. Evidence regarding whether non–β-lactam prophylaxis increases SSI risk across various surgical settings has remained inconsistent, motivating this large-scale analysis.

Researchers conducted a retrospective cohort study using a prospectively maintained database at a quaternary health center. The cohort included 41,100 patients undergoing 49,279 procedures across 10 surgical specialties between January 2021 and February 2024. Exposures of interest included perioperative antibiotic choice and reported β-lactam allergy, with additional covariates such as demographics, comorbidities, and procedural details. The primary outcome was SSI incidence within 30 to 90 days postoperatively.

Overall, procedures involving non–β-lactam antibiotic prophylaxis were associated with a higher SSI incidence than those using β-lactams (2.2% vs 1.3%; RR, 1.69; 95% CI, 1.28–2.01; P < .001). Similarly, procedures in patients reporting β-lactam allergy showed a higher unadjusted SSI rate (1.8% vs 1.3%; RR, 1.38; 95% CI, 1.15–1.64; P = .003).

After multivariable adjustment for covariates and allergy status, non–β-lactam use remained independently associated with increased SSI risk (OR, 1.33; 95% CI, 1.00–1.74; P = .04), whereas β-lactam allergy itself was not significantly associated (OR, 1.21; 95% CI, 0.97–1.49; P = .09). In subspecialty analyses, orthopedic surgery showed the strongest relationship, with non–β-lactam use tripling the odds of infection (OR, 3.01; 95% CI, 1.41–6.01; P = .003).

Based on the study results, the authors emphasized that an allergy-focused stewardship program can markedly reduce unnecessary use of non–β-lactam antibiotics, reinforcing the value of accurate allergy verification in surgical care.

“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,” the authors concluded.

Reference
Agarwal P, Kumar RP, Oleksiuk L-M, et al. Non–β-lactam antibiotic use, β-lactam allergy, and surgical site infections. JAMA Surg. Published online October 1, 2025. doi:10.1001/jamasurg.2025.3789