Highlights
- Formal reclassification of penicillin allergy labels led to a massive increase in the adoption of intracameral cefuroxime for cataract surgery prophylaxis.
- The suppression of automated electronic medical record (EMR) alerts for cephalosporin cross-reactivity, combined with pharmacy collaboration, moved the mean rate of cefuroxime use from 2% to 71% (adjusted).
- Evidence suggests that less than 1% of patients with a penicillin allergy label have a true, clinically significant allergy, yet these labels historically dictate suboptimal antibiotic selection.
- The study demonstrates that institutional policy interventions can effectively bridge the gap between evidence-based guidelines and clinical practice.
The Clinical Dilemma of Penicillin Allergy Labels in Ophthalmology
Cataract surgery is one of the most frequently performed surgical procedures worldwide. To prevent the devastating complication of endophthalmitis, the use of intracameral antibiotics—specifically second-generation cephalosporins like cefuroxime—has become the gold standard, supported by the landmark European Society of Cataract and Refractive Surgeons (ESCRS) study. However, a significant barrier to the use of cefuroxime is the prevalence of penicillin allergy labels in patient medical records. Approximately 10% of the population carries such a label, yet clinical immunology confirms that fewer than 1% of these individuals have a true, IgE-mediated allergy. Furthermore, the cross-reactivity between penicillin and second-generation cephalosporins is clinically negligible.Despite this evidence, surgeons frequently opt for alternative prophylaxis, such as moxifloxacin or topical antibiotics, when a penicillin allergy is noted, often due to automated EMR warnings or fear of medicolegal repercussions. This practice not only deviates from the most robust evidence-based prophylaxis but also contributes to broader issues of antibiotic stewardship.
Study Methodology: A Quality Improvement Approach
A quality improvement (QI) study was conducted at a large tertiary eye care center in the United States to address this disparity. The study included 1,905 patients with penicillin allergy labels undergoing cataract surgery between May 30, 2020, and May 30, 2025. This cohort accounted for 3,077 total surgical procedures performed by 51 different surgeons.The core of the study was a policy intervention implemented on November 30, 2022. The intervention was multi-faceted, designed to remove the systemic barriers preventing cefuroxime use. Key components included:
Enhanced Pharmacy Collaboration
Pharmacists were integrated into the perioperative workflow to review allergy histories and provide guidance to surgical teams regarding the safety of cephalosporins in patients with non-anaphylactic penicillin histories.
EMR Alert Suppression
The institution suppressed automated EMR alerts that warned of cross-reactivity between penicillin and cephalosporins. These alerts, often perceived as ‘nuisance alerts,’ frequently lead to alert fatigue and reflexive avoidance of the indicated drug.
Allergy Reclassification
The policy encouraged the formal reclassification of allergies in the medical record, moving patients from a generic ‘penicillin allergy’ to a more nuanced description or removing the label entirely when appropriate.The primary outcome was the rate of perioperative antibiotic selection, comparing the receipt of intracameral cefuroxime (1.0 mg/0.1 mL) against intracameral moxifloxacin (0.5 mg/0.1 mL), topical antibiotics, or no prophylaxis.
Significant Gains in Evidence-Based Antibiotic Selection
The results of the intervention were immediate and profound. In an unadjusted time series analysis, the mean rate of cefuroxime use jumped to 80.0% (95% CI, 74.5%-84.7%) following the policy change. This was in stark contrast to the expected use rate of only 3.3% (95% CI, 2.0%-4.4%) based on historical trends (P = .001).After adjusting for patient and surgeon variables, the mean rate of cefuroxime use was found to be 71% (95% CI, 62%-79%) post-intervention, compared to a baseline of just 2% (95% CI, 1%-3%) before the policy was enacted. This shift represents a fundamental change in the standard of care for this patient population at the study institution.
Addressing High-Risk Allergy Labels and Cross-Reactivity
One of the most critical aspects of the study was how the intervention handled patients with ‘high-risk’ allergy histories, such as those with noted anaphylaxis or angioedema. Even in these cases, the adjusted odds ratio for cefuroxime use after the policy intervention was 0.37 (95% CI, 0.27-0.52; P < .001). While surgeons remained more cautious with high-risk labels, the intervention still significantly increased the likelihood of these patients receiving the preferred antibiotic compared to the pre-intervention period.The study highlights that the 'allergy label' is often a poorly defined catch-all that includes non-allergic side effects (like nausea) or distant childhood events that have no bearing on current surgical safety. By requiring a review of the allergy history and providing pharmacy support, the institution empowered surgeons to make decisions based on pharmacological reality rather than legacy data entry.
Expert Commentary: Navigating the Gap Between Label and Reality
The findings by Reddy and colleagues underscore a critical theme in modern medicine: the EMR is both a tool and a hurdle. Automated alerts, while designed for safety, often fail to account for the low cross-reactivity between penicillins and later-generation cephalosporins. Cefuroxime has a distinct R1 side chain compared to penicillin G, which is the primary reason for the low cross-reactivity.Guideline bodies in both allergy and ophthalmology have long advocated for ‘de-labeling’ patients. This study provides a blueprint for how this can be achieved at scale. By shifting the burden of proof from the surgeon to a collaborative system (pharmacy + updated EMR logic), the institution successfully optimized patient care. However, it is important to note that such interventions require significant cross-departmental buy-in and a robust pharmacy department, which may not be available in all smaller surgical centers.The study’s limitations include its setting at a single tertiary center, which may limit generalizability. Furthermore, while the increase in cefuroxime use is a proxy for better adherence to prophylaxis guidelines, the study was not powered to detect changes in the already low rates of post-operative endophthalmitis.
Conclusion: A Blueprint for Antibiotic Stewardship
The rapid and sustained increase in cefuroxime use following the policy intervention suggests that surgeons are willing to follow evidence-based guidelines when institutional barriers are removed. Education alone is often insufficient to change long-standing clinical habits; however, when education is paired with structural changes—such as EMR alert suppression and pharmacy support—significant behavioral shifts are possible.This research serves as a call to action for surgical centers to review their penicillin allergy protocols. Reclassifying these labels is not merely an administrative task; it is a clinical intervention that ensures patients receive the most effective prophylaxis available, thereby reducing the risk of surgical complications and improving overall healthcare quality.
References
1. Reddy K, Workman P, Eschenauer G, Bixler J, Mian SI. Intracameral Cefuroxime Use in Cataract Surgery After Penicillin Allergy Reclassification. JAMA ophthalmology. 2026-03-05. PMID: 41784986.
2. Endophthalmitis Study Group, European Society of Cataract and Refractive Surgeons. Prophylaxis of postoperative endophthalmitis following cataract surgery: results of the ESCRS multicenter study and identification of risk factors. J Cataract Refract Surg. 2007;33(6):978-988.
3. Shenoy ES, Macy E, Rowe T, Blumenthal KG. Evaluation and Management of Penicillin Allergy: A Review. JAMA. 2019;321(2):188-199.