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. 2025 Oct 1;8(10):e2540809.
doi: 10.1001/jamanetworkopen.2025.40809.

β-Lactam vs Non-β-Lactam Antimicrobial Prophylaxis and Surgical Site Infection

Selina Largiadèr  1 , Delphine Berthod  2 , Andreas Widmer  3 , Nicolas Troillet  2 , Holly Jackson  4 , Christelle Perdrieu  2 , Stephan Harbarth  4 , Rami Sommerstein  1   5 ; Swissnoso Group
Collaborators, Affiliations

β-Lactam vs Non-β-Lactam Antimicrobial Prophylaxis and Surgical Site Infection

Selina Largiadèr et al. JAMA Netw Open. .

Abstract

Importance: β-lactam-based surgical antimicrobial prophylaxis (SAP) is the standard for most surgical procedures. Alternatively, and mostly due to allergies, non-β-lactam-based prophylaxis is used. The association between the use of non-β-lactam SAP and an increased risk of surgical site infection (SSI) rate has not yet been conclusively described.

Objective: To assess whether non-β-lactam vs β-lactam prophylaxis is associated with the occurrence of SSI.

Design, setting, and participants: This cohort study was based on the Swissnoso SSI surveillance system of 175 hospitals, including adult patients who underwent a major surgical procedure with SAP administration within 120 minutes prior to incision and postdischarge follow-up from January 2009 to December 2020. Patients with wound contamination class IV were excluded. Data analysis was conducted from July to December 2024.

Exposures: β-Lactam SAP vs non-β-lactam SAP.

Main outcomes and measures: The main outcome was occurrence of SSI, according to Centers for Disease Control and Prevention definitions. Mixed-effects logistic regression models were used to adjust for institutional, patient, and perioperative confounding factors.

Results: Of 538 976 surveilled patients, 348 885 (196 411 [56.3%] female; median [IQR] age, 63.2 [47.0-73.3] years) fulfilled eligibility criteria. β-Lactam SAP was administered in 342 936 patients (98.3%) and non-β-lactam SAP in 5949 patients (1.7%). SSI was diagnosed in 9507 patients (2.8%) exposed to β-lactam SAP vs 364 patients (6.1%) who received non-β-lactam SAP (P < .001). Non-β-lactam SAP was significantly associated with a higher SSI rate (adjusted odds ratio [aOR], 1.78; 95% CI, 1.59-1.99; P < .001) compared with β-lactam SAP. A higher SSI rate for non-β-lactam SAP was found across all procedure types. Secondary analyses found a higher risk of SSI for ciprofloxacin (aOR, 1.57; 95% CI, 1.33-1.87; P < .001), vancomycin (aOR, 1.38; 95% CI, 1.03-1.86; P = .04), and clindamycin (aOR, 2.12; 95% CI, 1.82-2.47; P < .001) compared with β-lactam SAP.

Conclusions and relevance: In this large cohort study, administration of non-β-lactam SAP was associated with 1.8-fold higher odds of SSI. These findings suggest that non-β-lactam SAP should be avoided whenever possible. A careful evaluation of patients with reported β-lactam allergy should be performed before administering a second-choice antibiotic.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Sommerstein reported receiving grants from BBraun Switzerland, nonfinancial support from Pfizer (paid to institution), and grants from Schülke (paid to institution) outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Participant Flowchart
SAP indicates surgical antimicrobial prophylaxis; SSI, surgical site infection.
Figure 2.
Figure 2.. Mean Raw Infection Rate Per Procedure Type for β-Lactam vs Non–β-Lactam Surgical Antimicrobial Prophylaxis
See this image and copyright information in PMC

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