Highlight
– Surgical site infections (SSIs) remain a significant postoperative complication with important clinical and economic burdens.
– Use of β-lactam antibiotics for prophylaxis is associated with a significantly lower rate of SSIs compared to non-β-lactam antibiotics.
– Reported β-lactam allergy is associated with higher SSI incidence but is not an independent predictor after adjusting for antibiotic choice and other covariates.
– Implementation of allergy-focused antibiotic stewardship protocols decreases non-β-lactam antibiotic use and may reduce SSI rates, especially in orthopedic surgery.
Study Background and Disease Burden
Surgical site infections are among the most common healthcare-associated infections, occurring in 1-3% of all surgeries and leading to increased morbidity, prolonged hospital stays, need for reoperations, and elevated healthcare costs. Effective antimicrobial prophylaxis is a cornerstone in SSI prevention. β-lactam antibiotics, particularly cephalosporins, are the preferred agents due to their broad-spectrum activity, safety profile, and pharmacokinetics suitable for surgical prophylaxis.
However, approximately 10% of patients report a β-lactam allergy, often leading clinicians to select alternative non-β-lactam agents such as clindamycin or vancomycin for prophylaxis. There is conflicting evidence about the effectiveness of non-β-lactam agents in preventing SSIs, with some studies suggesting higher SSI risk. The impact of reported β-lactam allergy on infection risk independent of antibiotic choice has not been fully elucidated.
Study Design
This retrospective cohort study utilized a prospectively collected database at a quaternary health center, including all surgical procedures from January 2021 to February 2024. A total of 49,279 procedures from 10 surgical specialties involving 41,100 patients were analyzed. The primary exposures examined were antibiotic choice—β-lactam versus non-β-lactam prophylaxis—and patient-reported β-lactam allergy status.
Covariates accounted for included demographic variables (age, sex), comorbidities, and detailed surgical procedure characteristics. The primary outcome was the incidence of SSI within 30 to 90 days postoperatively, determined through standardized surveillance methods.
Statistical analyses included calculation of risk ratios for crude associations and multivariable logistic regression to adjust for confounding factors.
Key Findings
The overall SSI rate was 1.4%. Procedures in which non-β-lactam antibiotics were used showed a significantly higher SSI incidence of 2.2% compared to 1.3% in β-lactam prophylaxis (risk ratio [RR] 1.69; 95% CI, 1.28–2.01; P < .001). Patients reporting a β-lactam allergy also had a higher SSI incidence of 1.8% versus 1.3% in those without such an allergy (RR 1.38; 95% CI, 1.15–1.64; P = .003).
In multivariable logistic regression adjusting for demographics, comorbidities, procedure specifics, and allergy status, non-β-lactam antibiotic use remained significantly associated with increased SSI risk (odds ratio [OR] 1.33; 95% CI, 1.00–1.74; P = .04). However, the association between reported β-lactam allergy and SSI became nonsignificant after adjustment (OR 1.21; 95% CI, 0.97–1.49; P = .09).
Subspecialty analysis revealed that the increased SSI risk associated with non-β-lactam antibiotics was prominent and statistically significant only within orthopedic surgery (OR 3.01; 95% CI, 1.41–6.01; P = .003), signifying a particular vulnerability in this group.
An important institutional intervention during the study period was the introduction of an allergy-focused antibiotic stewardship guideline, which led to a marked reduction in non-β-lactam antibiotic use by better allergy assessment and classification.
Expert Commentary
This large cohort confirms previous smaller studies suggesting that β-lactam antibiotics remain superior for surgical prophylaxis in preventing SSIs. The findings underscore the clinical consequences of reported β-lactam allergy, which often leads to use of potentially less effective alternative agents. Since many reported β-lactam allergies are not true IgE-mediated hypersensitivities, unnecessary avoidance of β-lactams may inadvertently increase SSI risk.
Experts emphasize the importance of allergy verification strategies, including detailed patient history and, where feasible, skin testing or graded challenges, to safely reintroduce β-lactam antibiotics when appropriate. This stewardship approach minimizes reliance on broader-spectrum or less-efficacious non-β-lactam alternatives.
The pronounced effect in orthopedic surgery aligns with the high stakes of preventing deep SSIs involving implants, where infection consequences are severe. Incorporating allergy assessments into preoperative planning in this specialty is especially critical.
Limitations include the retrospective design and potential residual confounding inherent in observational studies. Despite adjustments, unmeasured factors could influence results. The study reflects practice in a single quaternary center, which may limit generalizability.
Conclusion
This study provides compelling evidence that β-lactam antibiotic prophylaxis is associated with significantly lower SSI rates compared to non-β-lactam agents. Reported β-lactam allergy is not independently predictive of SSI after controlling for antibiotic choice and other factors, highlighting that allergy status primarily influences SSI risk through altered prophylaxis.
These findings support the necessity of precise and rigorous allergy assessment to avoid unneeded use of alternative antibiotics that may be less effective. Implementation of allergy-focused stewardship protocols can reduce non-β-lactam antibiotic use and improve clinical outcomes, particularly in orthopedic surgery where SSI consequences are most critical.
Future research should explore prospective allergy verification strategies and their integration into surgical pathways to optimize prophylaxis and minimize SSI risk. Clinicians should maintain a heightened awareness regarding the ramifications of antibiotic choice and allergy labels to enhance patient safety and surgical outcomes.
References
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