Fatal anaphylactic shock following cefoperazone–sulbactam re-exposure: a short report on systemic gaps in adverse drug reaction management

Abstract

This report presents a case of fatal anaphylactic shock following re-exposure to cefoperazone-sulbactam, highlighting systemic gaps in adverse drug reaction (ADR) management. The patient initially tolerated the drug without immediate adverse effects but developed severe hypersensitivity reactions upon subsequent exposures, ultimately leading to death. Analysis revealed that the healthcare team underestimated the risk of delayed IgE-mediated sensitization, and critical allergy information was not documented in the emergency department (ED). Additionally, the electronic health record (EHR) system lacked real-time allergy alerts. Fragmented communication during care transitions and technological deficiencies further exacerbated the risks.

Introduction

Cefoperazone–sulbactam, a β-lactam/β-lactamase inhibitor combination, is widely used for multidrug-resistant infections.¹ While effective, it carries a risk of severe hypersensitivity reactions, including anaphylactic shock. Cross-reactivity with penicillin allergies and delayed sensitisation further complicates its safety profile.² Despite guidelines advocating rigorous adverse drug reaction (ADR) monitoring, systemic failures persist, particularly in documentation and interdisciplinary communication.³ This case highlights critical vulnerabilities in ADR management and proposes actionable solutions.

Case presentation

Clinical timeline

November 2022: The patient received cefoperazone–sulbactam for 11 days during hospitalisation for bronchial infection, with no immediate adverse reactions.

January 2023: Readmitted for respiratory exacerbation, she received cefoperazone–sulbactam in the emergency department (ED). Within 13 min, she developed cyanosis and diaphoresis, misattributed to acute heart failure. The ED failed to document the suspected ADR. After resuscitation, she was transferred to the intensive care unit (ICU), where she was prescribed meropenem for anti-infection treatment.

February 2023: After stabilisation in the ICU, cefoperazone–sulbactam was readministered in the respiratory ward. Within 19 min, she experienced fatal anaphylactic shock (Naranjo score: 9). Despite resuscitative efforts in the ICU, the patient died 16 hours later.

Systemic failures identified

Unrecognised sensitisation: clinicians underestimated the latency of IgE-mediated sensitisation, which persisted for months after initial exposure.

Fragmented documentation: the ED omitted critical ADR data, and handovers between ICU and respiratory ward lacked allergy history updates.

Absence of allergy alerts: the electronic health record (EHR) system fails to trigger alerts when prescribing cross-reactive medications such as cephalosporins to penicillin-allergic patients.

Adverse event analysis

Immunological mechanism

Cefoperazone’s R1 side chain acts as a primary antigenic determinant, inducing IgE-mediated sensitisation. Subsequent re-exposure triggers mast cell degranulation, leading to anaphylaxis. Penicillins and cephalosporins exhibit a degree of cross-allergic reactivity due to shared β-lactam structures.⁴ Nevertheless, penicillin allergy is not an absolute contraindication for cefoperazone–sulbactam as its significant structural divergence in side chains from penicillin confers a low risk of cross-reactivity. The American Academy of Allergy, Asthma & Immunology guidelines state that cephalosporins with structurally dissimilar side chains (eg, third-generation agents) may be cautiously administered to penicillin-allergic patients, whereas avoidance remains imperative in cases of severe hypersensitivity reactions.⁵

Systemic vulnerabilities

• 1. Documentation gaps

• • Upon admission, the patient’s self-reported allergy history to penicillin and streptomycin was explicitly documented in the ‘Front Page/Chief Complaint Section’ of the EHR and confirmed by the healthcare team. Despite this documentation, the emergency physician neither recognised nor recorded this critical allergy information during the initial ADR event. This oversight resulted in subsequent care teams being deprived of essential allergy data, constituting a direct violation of WHO’s pharmacovigilance standards.

• • Incomplete handovers during care transitions amplified risks, as highlighted in studies on communication breakdowns.⁶

• 2. Technology deficiencies: the hospital’s EHR lacked real-time allergy alerts, a proven safeguard against high-risk prescriptions.⁷

• 3. Training gaps: clinicians displayed limited awareness of cephalosporin sensitisation timelines and cross-reactivity risks, underscoring the need for targeted training.⁸

Recommendations for systemic improvement

1. Structured ADR documentation: implement mandatory EHR templates with fields for suspected ADRs, temporal relationships and severity grading.

2. Real-time allergy alerts: integrate pop-up alerts for high-risk medications (eg, cephalosporins in penicillin-allergic patients), requiring pharmacist verification.

3. Interdisciplinary training: conduct simulations on anaphylaxis recognition and ADR documentation for ED, ICU and ward staff.

4. Patient engagement: provide allergy wristbands and multilingual educational materials to empower patient advocacy.

Conclusion

This case underscores lethal consequences of systemic failures in ADR management. Standardised documentation, technology-driven alerts and interdisciplinary collaboration are imperative to prevent recurrent harm. Future efforts should evaluate the scalability of these interventions across healthcare networks.