Discussion

Using a NSQIP-sampled, surgically diverse cohort spanning an 18-month period, a reported β-lactam allergy was associated with an increased risk of SSI. This effect was completely mediated by receipt of an alternate antibiotic to cefazolin. Our findings add to the mounting evidence demonstrating the harms of avoiding preferred β-lactam antibiotic due to reported allergy. In the perioperative setting, it is imperative that surgeons and anesthesiologists carefully assess patient-reported β-lactam allergies because emerging literature indicates that most patients can tolerate cefazolin.^{Reference Zagursky and Pichichero2}

One prior study assessed the relationship between reported penicillin allergy and the risk of SSI. Blumenthal et al^{Reference Blumenthal, Ryan, Li, Lee, Kuhlen and Shenoy6} conducted a 5-year retrospective review of 9,004 surgical procedures and reported an adjusted odds ratio of 1.51 for developing a SSI in those with a reported penicillin allergy.^{Reference Blumenthal, Ryan, Li, Lee, Kuhlen and Shenoy6} In their study, this association was completely mediated by receipt of a non–β-lactam antibiotic but was limited to 5 surgical procedures: coronary artery bypass, colon surgery, hip arthroplasty, hysterectomy, and knee arthroplasty.^{Reference Blumenthal, Ryan, Li, Lee, Kuhlen and Shenoy6}

Our study strengthens the external validity of the association between reported allergy and SSI. In contrast to Blumenthal et al,^{Reference Blumenthal, Ryan, Li, Lee, Kuhlen and Shenoy6} our study included 7 surgical specialties encompassing >20 different surgical procedures. Our findings suggest that improving the use of β-lactam prophylaxis among these patients could have a widespread impact on SSIs across surgical specialties. In addition, our study included patients who reported any β-lactam allergy rather than penicillin allergy alone. We hypothesize that the impact of a reported penicillin allergy is not drug specific but, rather, applies to all β-lactam antibiotics, since both result in the avoidance of cefazolin. Patient and physician misconceptions surrounding penicillin allergy and cross reactivity with cephalosporins are prevalent,^{Reference Vorobeichik, Weber and Tarshis13} and interventions are urgently needed for clinicians to accurately assess a reported allergy and to determine whether they can safely receive cefazolin. Interventions such as β-lactam skin testing^{Reference Li, Markus, Osmon, Estes, Gosselin and Hanssen14–Reference Moussa, Shuster and Matte19} and oral provocation challenges^{Reference McDanel, Azar and Dowden18–Reference Savic, Gurr and Kaura20} have been used in the perioperative setting but have been limited in their scalability and sustainability due to resource requirements. It is now recognized that the cephalosporin cefazolin is non–cross-reactive with penicillin due to a structurally dissimilar side chain,^{Reference Zagursky and Pichichero2} which suggests that the decision to administer cefazolin preoperatively could theoretically be achieved with a clinical history alone. Further studies are needed to determine whether such a strategy is sustainable and whether an increase in cefazolin use in the patients with reported β-lactam allergy results in a decline in SSIs.

Our study provides additional insight into preoperative antibiotic use and the mediators of SSI. In the study by Blumenthal et al, 34.7% of patients who reported penicillin allergy received vancomycin as an alternate antibiotic.^{Reference Blumenthal, Ryan, Li, Lee, Kuhlen and Shenoy6} Preoperative administration of vancomycin is fraught with challenges, including the need for more stringent weight-based dosing, and unique to vancomycin, initiation of the antibiotic infusion ideally 60–120 minutes before surgical incision.^{Reference Bratzler, Dellinger and Olsen1} The challenges with antibiotic administration are reflected in the study by Blumenthal et al, in which 97.5% of patients did not receive vancomycin in the recommended time frame.^{Reference Blumenthal, Ryan, Li, Lee, Kuhlen and Shenoy6} Given that one-third of their patients with reported β-lactam allergy received this antibiotic, it was unclear whether inferior antibiotic efficacy or inappropriate timing of alternate antibiotics was the main contributor to the increased SSI risk. In contrast, vancomycin utilization as preoperative prophylaxis at our institution is significantly lower; only 2.2% of patients with reported β-lactam allergy received this antibiotic. By demonstrating a similar mediation effect, combined with negligible use of vancomycin, our study strongly suggests that inferior efficacy of alternate antibiotic agents is the main explanation for the increased SSI risk observed among patients with reported β-lactam allergy.

Our study has several limitations. First, the prevalence of reported β-lactam allergy (10.3%) is probably underestimated in our study because accessibility to inpatient and outpatient allergy testing services at our institution likely resulted in de-labeling of a significant proportion of patients.^{Reference Leis, Palmay and Ho21} Similarly, cefazolin use in patients with reported β-lactam allergy were 3× higher (38.8%) compared to the results reported by Blumenthal et al (12.2%).^{Reference Blumenthal, Ryan, Li, Lee, Kuhlen and Shenoy6} Therefore, the impact of a reported allergy on SSI may be more pronounced at other institutions where preoperative cefazolin utilization is lower. Second, we used the NSQIP-defined 30-day SSI outcome variable; thus, our study may not have included late-onset SSIs. Whether these would be affected by reported β-lactam allergy in the same way is unknown. Third, we cannot exclude the possibility of residual confounding variables, which could not be included due to limitations in sample size and outcome frequency. Finally, the findings of this study cannot be applied to transurethral procedures because they were excluded from this study.

A self-reported β-lactam allergy is associated with increased odds of SSI across a broad range of surgical specialties, which appears to be mediated by the use of alternate agents to intravenous cefazolin. Given recent data suggesting that cefazolin is a non–cross-reactive cephalosporin, there is great opportunity to improve SSI rates through interventions that promote the safe use of cefazolin prophylaxis among patients reporting a β-lactam allergy.