TOPLINE:

Surgical antimicrobial prophylaxis using non-beta‑lactams administered before major surgery was independently associated with a significantly higher risk for surgical site infection than conventional prophylaxis with beta‑lactams; this increased risk was consistent across all surgical procedure types.

METHODOLOGY:

• Investigators in Switzerland conducted a retrospective cohort study of 348,885 patients (median age, 63.2 years; 56.3% women) from 175 healthcare institutions to assess whether surgical antimicrobial prophylaxis using non-beta‑lactams vs conventional prophylaxis using beta‑lactams was associated with an increased risk for surgical site infection.
• All patients underwent major surgery. Of them, 342,936 received beta-lactams (cefuroxime or cefazolin), and 5949 received non-beta-lactam agents (ciprofloxacin, vancomycin, or clindamycin); all antibiotics were administered within 120 minutes before incision.
• The primary outcome was the occurrence of surgical site infection within 30 days, extended to 1 year for procedures involving implants, as defined by the Centers for Disease Control and Prevention.

TAKEAWAY:

• Overall, 2.8% of patients developed surgical site infections; the incidence was significantly higher in the non-beta-lactam group than in the beta-lactam group (6.1% vs 2.8%; P < .001).
• Compared with beta-lactam prophylaxis, non-beta-lactam prophylaxis was independently associated with a nearly 1.8-fold higher odds of surgical site infection (adjusted odds ratio [aOR], 1.78; P < .001).
• Non-beta-lactam prophylaxis was also linked to higher rates of surgical site infection across all surgical procedure types than beta-lactam prophylaxis, with the association most pronounced for superficial incisional infections (aOR, 2.16; P < .001).
• Among non-beta-lactam agents, clindamycin carried the highest risk (aOR, 2.12), followed by ciprofloxacin (aOR, 1.57) and vancomycin (aOR, 1.38), each compared with beta‑lactam agents.

IN PRACTICE:

"These findings have important clinical implications, suggesting that beta-lactam prophylaxis should be prioritized whenever possible. Patients with self-reported or poorly documented beta-lactam allergy should be carefully evaluated before administering a second-line non-beta-lactam SAP [surgical antimicrobial prophylaxis]," the investigators wrote.

SOURCE:

The study was led by Selina Largiadèr, MSc, Faculty of Health Sciences and Medicine, University of Lucerne, Lucerne, Switzerland. It was published online on October 31, 2025, in JAMA Network Open.

LIMITATIONS:

Because the study was retrospective with a limited number of predefined variables, it failed to capture potential confounders such as diabetes, perioperative glycaemia, and immunosuppression. The lack of information on beta‑lactam allergy status and institutional protocols obscured the rationale for choosing non‑beta‑lactam agents. Moreover, limiting the analysis to five agents and excluding 129,741 patients who had received other or combination prophylaxis potentially affected the study's generalisability. 

DISCLOSURES:

No funding source was reported. One author disclosed receiving grants from B. Braun Switzerland and Schülke and non‑financial support from Pfizer, all unrelated to the submitted work. The Schülke grant and Pfizer support were paid to the author's institution.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.