Ceftriaxone-Induced Anaphylactic Shock: A Case of Cross-Reactivity in a Critically Ill Patient

Document Type

Conference Proceeding

Publication Date

10-2025

Publication Title

CHEST

Abstract

INTRODUCTION: Cephalosporins are commonly prescribed in intensive care due to their broad-spectrum antimicrobial coverage. However, they are also among the most common causes of adverse drug reactions(1,2). Immediate hypersensitivity reactions include urticaria, angioedema, bronchospasm, and anaphylaxis(1). While anaphylactic reactions to cephalosporins are rare, occurring in approximately 1-3% of those exposed, they can be life threatening(2). We present a case of anaphylactic shock requiring intubation following ceftriaxone administration.

CASE PRESENTATION: A 90s-year-old woman with past medical history of remote penicillin allergy presented to the emergency department (ED) with malaise, subjective fevers, and poor oral intake. She was lethargic, hypotensive, and required fluid resuscitation, vasopressor support, and broad-spectrum antibiotic treatment (cefepime and vancomycin). The patient was admitted to the intensive care unit (ICU) for septic shock secondary to infectious enteritis seen on CT imaging, complicated by streptococcus bacteremia. Her shock improved overnight, and she was planned for transfer out of the ICU. The antibiotic regimen was de-escalated to ceftriaxone and metronidazole. Approximately 30 minutes after receiving ceftriaxone she developed cyanosis, hypotension, and severe respiratory distress requiring endotracheal intubation. Laboratory workup revealed profound lactic acidosis. Imaging studies ruled out pneumothorax and pulmonary embolism. A bronchoscopy showed normal lungs, ruling out aspiration. Intubation triggered unstable atrial fibrillation requiring multiple cardioversions. The following day, after receiving her second dose of ceftriaxone, peak pressures on the ventilator rose, consistent with severe bronchospasm. Ceftriaxone was switched to linezolid in consultation with infectious disease. Tryptase levels were elevated at 26 µg/L, decreasing to 14 µg/L after 24 hours (normal < 11µg/L). The patient improved, was extubated, and made a full recovery.

DISCUSSION: Differential diagnoses for acute hypoxic respiratory failure include pulmonary embolism, aspiration, pulmonary edema, and anaphylaxis(3). Given the temporal association with ceftriaxone administration, recurrent bronchospasm, and elevated tryptase, we highly suspected anaphylactic shock. Although the patient had a prior documented penicillin allergy, only 1-4% of patients with this history exhibit true cephalosporin sensitivity(2). Additionally, even in patients with documented IgE-mediated penicillin allergy, 80% lose their sensitivity after 10 years(2). Cephalosporins are beta-lactam antibiotics with two side chains, R1 and R2(2). Cross-reactivity between penicillin and a third-generation cephalosporin (ceftriaxone) is rare (around 1%). However, cross-reactivity between cephalosporins is more common. This is especially apparent when they share similar R1 side chains, such as cefepime and ceftriaxone, which share an identical R1 side chain(2). Here, sensitization likely occurred with cefepime, leading to an IgE-mediated cross-reaction and subsequent anaphylactic shock upon ceftriaxone administration. Skin prick and intradermal testing can assess cephalosporin allergy. However, these tests have a high false-positive rate and are not routinely used inpatient in the United States(4).

CONCLUSIONS: Initial management of anaphylactic shock includes administration of intramuscular epinephrine, stabilization of vital signs, and identification of potential triggers. In patients with anaphylaxis related to cephalosporins, prompt substitution with an alternative antibiotic is crucial. If no suitable alternative is available, selecting a cephalosporin with a dissimilar R1 side chain can reduce cross-reactivity. A high index of suspicion is vital for the timely identification and treatment of this life-threatening condition.

Volume

168

Issue

4 Suppl

First Page

A110

Comments

CHEST Annual Meeting, October 19-22, 2025, Chicago, IL

Last Page

A111

DOI

10.1016/j.chest.2025.07.061

ISSN

0012-3692

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