A large cohort study conducted in Switzerland suggests that use of non-beta-lactam antibiotics before surgery should be avoided when possible, the researchers have reported in JAMA Network Open.
The study of nearly 350 000 adults who were administered surgical antibiotic prophylaxis (SAP) before a major surgical procedure found that use of non-beta lactam antibiotics was associated with a nearly twofold increase in the surgical-site infection (SSI) rate compared with those who received SAP with beta-lactam antibiotics, reports CIDRAP.
Beta-lactam antibiotics such as cefazolin and cefuroxime are the first-line choices for SAP for most surgical procedures to mitigate the risk of SSIs, which are a common complication after surgery and can extend hospitalisations, increase healthcare costs, and contribute to patient mortality. SSIs are estimated to occur in one in 30 procedures.
Beta-lactams are recommended for SAP because of their broad-spectrum, bactericidal activity, and safety profile. Patients with self-reported or documented beta-lactam allergies, however, require alternative options.
The study authors say their findings indicate that those patients should be carefully evaluated before SAP is administered.
Higher SSI rate across all procedures
Using data from the Swissnoso SSI surveillance system, a team of Swiss researchers analysed data on all patients who received SAP with either beta-lactam or non–beta lactam antibiotics at least 120 minutes before incision at 175 participating hospitals from 2009 until 2020.
Patients who had undergone one of the 10 most frequent surgical procedures were included. The main outcome was occurrence of SSIs.
“The comparative effectiveness of non–β-lactam vs β-lactam SAP in preventing SSIs remains incompletely characterised,” they wrote. “While β-lactam antibiotics are preferentially recommended, studies suggest that non–β-lactam alternatives may be associated with elevated SSI rates.”
Of the 538 976 surveilled patients, 348 885 (median age, 63.2 years; 56.3% female) were included in the study. Of these patients, 342 936 (98.3%) received beta-lactam SAP and 5 949 (1.7%) received non–beta-lactam SAP. Patients who received beta-lactam SAP were given cefuroxime (75.1%) and cefazolin (24.9%), while patients who received non–beta-lactam SAP were given clindamycin (53.6%), ciprofloxacin (30.5%), and vancomycin (16%).
Of the 9 871 patients who were diagnosed as having SSIs, 9 507 (2.8%) were in the beta-lactam group and 364 (6.1%) in the non–beta-lactam group. The non–beta-lactam SAP group consistently had higher rates of superficial incisional infections (2.9% vs 1.0%), deep incisional infections (1.0% vs 0.4%), and organ-space infections (2.3% vs 1.3%).
After adjustments for institutional, patient, and perioperative confounding factors, non–beta-lactam SAP was significantly associated with a higher SSI rate (adjusted odds [aOR], 1.78) compared with beta-lactam SAP. The higher SSI rate was found across all surgical procedures.
A propensity score-based and matched analysis confirmed the higher SSI risk associated with non–beta-lactam SAP (aOR, 1.68). Secondary analyses found a higher risk of SSI for ciprofloxacin (aOR, 1.57), vancomycin (aOR, 1.38), and clindamycin (aOR, 2.12) compared with beta-lactam SAP.
Pre-operative allergy testing recommended
The authors say the findings are consistent with a 2017 study that found a 50% increased likelihood of SSIs in patients with penicillin allergy who received alternative prophylactic antibiotics.
“Our study extends these findings, yielding more definitive results with a much larger sample size and direct comparison of β-lactam vs non–β-lactam prophylaxis, independent of allergy status,” they wrote.
They add that since penicillin allergies are frequently unconfirmed, surgeons should test their patients before resorting to alternative antibiotics. While an estimated 10% to 15% of adults carry a beta-lactam allergy label, research has shown that up to 90% of those with the label may actually be beta-lactam tolerant.
The authors note that studies have shown that preoperative allergy testing reduces non–beta-lactam SAP.
"These findings, coupled with the increased SSI risk associated with non–β-lactam SAP, as confirmed by our study, should motivate preoperative testing in case of uncertain penicillin allergy," they concluded.
Study details
β-Lactam vs Non–β-Lactam Antimicrobial Prophylaxis and Surgical Site Infection
Selina Largiadèr, Delphine Berthod, Andreas Widmer, et al.
Published in JAMA Network Open on 31 October 2025
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 post-discharge 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 Centres 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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