Multidisciplinary UPMC Study Links β-lactam Antibiotic Use to Lower Surgical Site Infection Rates

A new study published in JAMA Surgery and conducted across multiple surgical departments at UPMC found that use of β lactam antibiotics for surgical prophylaxis was associated with lower rates of surgical site infection (SSI) compared to non β lactam alternatives. The research analyzed patient data from a prospective institutional database containing surgical records from more than 49,000 procedures performed at UPMC Presbyterian and UPMC Shadyside between January 2021 and February 2024. The study also showed that a recorded β lactam allergy in patients did not independently predict infection once antibiotic selection was considered.

The study was a collaborative effort involving faculty from the Departments of Neurological Surgery; Pharmacy; Surgery; Infection Control; Epidemiology; Division of Infectious Diseases; and Division of Pulmonary, Allergy, Critical Care and Sleep Medicine. Prateek Agarwal, MD, MBA, chief resident in the Department of Neurological Surgery was the study’s first author. Robert M. Friedlander, MD, MA, chair of the Department of Neurological Surgery, Walter Dandy Distinguished Professor of Neurosurgery, Neurology, and Neurobiology, and co director of the UPMC Neurological Institute, was the senior author of the study.

"Our study is the largest to date demonstrating that use of non-beta-lactam antibiotic prophylaxis increases SSI rate and helps resolve conflicting evidence on the association of reported beta-lactam allergy and SSI,” says Dr. Prateek. “In addition to improving surgical outcomes, allergy-focused antibiotic stewardship is critical in the effort to control ballooning health care costs."

About the Study

Perioperative antimicrobial prophylaxis is a modifiable factor in SSI prevention. First generation cephalosporins, including cefazolin are preferred because of their narrow spectrum, tissue penetration, and safety. However, it is estimated that 8% to 20% of patients have a β lactam antibiotic allergy noted in their health record. This fact often leads to substitution with non β lactam agents like vancomycin or clindamycin.

The study conducted by Dr. Friedlander and colleagues examined if β lactam prophylaxis is associated with fewer SSI compared with the use non β lactam antimicrobials across various surgical specialties. The study also looked into whether a recorded β lactam allergy independently influences infection risk when antibiotic choice and clinical factors are added to the analysis.

Overview of Findings

Across the entire data set, patients who received β lactam antibiotics had a lower SSI rate than those who received non β lactam agents, 1.3% vs. 2.2%, respectively. When adjusting the analysis for demographic and procedural factors, Dr. Friedlander and colleagues found the use of a non β lactam agent was still associated with increased risk for SSI.

Even though patients with a recorded β lactam allergy had higher unadjusted rates of infection, the allergy label was not independently associated with infection once antibiotic choice was included in the analysis. A substantial portion of the observed risk in patients with a noted allergy was explained by receipt of non β lactam prophylaxis.

The overall rate of surgical site infection in the full study cohort was 1.4%. Most of the procedures were performed in general surgery, orthopaedic surgery, and neurological surgery. Of the 10 surgical specialties included in the study, orthopaedic surgery was the only one where non–β-lactam antibiotic use was statistically significantly associated with higher infection risk after adjusting for other factors.

“Our study reinforces that the antibiotic selected for prophylaxis and not the presence of an allergy label is the more important driver of infection risk,” says Dr. Friedlander.

Achieving Safe β lactam Use in Patients With a Reported Allergy

UPMC implemented a system-wide guideline in September 2022 to standardize β lactam allergy evaluation and promote appropriate use of β lactam agents for surgical patients when safe. The protocol includes a simplified perioperative decision algorithm, visual tools for classifying cutaneous reactions, a β lactam cross reactivity reference, and clinical decision trees for penicillin versus cephalosporin allergy histories. Following implementation of the protocol, the proportion of allergy labeled patients who still received a β lactam agent increased by about 22%, without an increase in SSI rates.

“Many patients with a β lactam allergy label can safely receive a first generation cephalosporin. By improving how we evaluate and act on our patient data relative to allergy status, we are protecting patients from unnecessary risk,” Dr. Friedlander says.

Implications of the Study for Surgical and Antimicrobial Stewardship Practices

The findings from Dr. Friedlander and colleagues research support perioperative stewardship practices that prioritize the use of β lactam prophylaxis when clinically appropriate, even including for many patients with a reported allergy after structured screening. Formal allergy testing is not always necessary prior to surgery; in many cases, an evidence-based, protocol-driven clinical assessment is enough to guide safe β lactam use while also avoiding unnecessary exposure to broader spectrum alternatives.

“It’s another tactic we can employ to keep our patients safe while also working on the persistent challenge of antimicrobial resistance,” Dr. Friedlander says.

Read more details about the study design and analysis using the link below to the full paper in JAMA Surgery.

Study Reference

• Agarwal P, Prem Kumar R, Oleksiuk L M, Crall V, Petrov AA, McCreary EK, Holder Murray J, Chang Y F, Agarwal N, Hamilton DK, Friedlander RM. 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.