Anaphylaxis (Type I IgE-Mediated Hypersensitivity Reaction)
This resident is experiencing anaphylaxis, a severe Type I IgE-mediated hypersensitivity reaction to ceftriaxone, characterized by the rapid onset (within 20 minutes) of wheezing, facial swelling (angioedema), and hypotension following the first dose of the antibiotic. 1
Clinical Reasoning
The presentation is classic for anaphylaxis based on several key features:
Timing: Symptoms developed within 20 minutes of IV ceftriaxone administration, which is consistent with immediate hypersensitivity reactions that typically occur within minutes to hours after drug exposure 2
Triad of life-threatening symptoms: The combination of respiratory compromise (wheezing/bronchospasm), cardiovascular collapse (hypotension), and angioedema (facial swelling) represents multi-system involvement characteristic of anaphylaxis 1, 3
First dose reaction: While anaphylaxis classically occurs after prior sensitization, ceftriaxone can cause anaphylaxis even on first exposure, as documented in multiple case reports 3, 4. The FDA label explicitly warns that "serious and occasionally fatal hypersensitivity reactions (i.e., anaphylaxis) have been reported" with ceftriaxone 1
Why This is Anaphylaxis and Not Other Reactions
Type I hypersensitivity (anaphylaxis) is distinguished from other drug reactions by:
- Immediate onset: True allergic reactions are immune-mediated, reproducible, and typically occur within minutes to hours 2
- Multi-system involvement: The presence of respiratory (wheezing), cardiovascular (hypotension), and dermatologic (facial swelling) symptoms simultaneously indicates systemic mast cell degranulation 5
- Severity: Hypotension with bronchospasm represents Grade 3/4 severity requiring immediate aggressive intervention 6
Critical Management Points
Immediate actions required (based on FDA labeling and guidelines):
- Discontinue ceftriaxone immediately 1
- Administer epinephrine 0.2-0.5 mg intramuscularly into the lateral thigh, repeat every 5-15 minutes as needed 5, 7
- Establish IV access and give normal saline 1-2 L at 5-10 mL/kg in first 5 minutes for hypotension 5
- Monitor continuously for cardiac complications, as asystole has been reported with ceftriaxone anaphylaxis 3
Important Clinical Caveats
Common pitfalls to avoid:
Do not assume prior tolerance predicts safety: Even patients who previously tolerated other cephalosporins can experience anaphylaxis to ceftriaxone due to its unique R2 side chain structure 8. Ceftriaxone has distinct antigenic determinants separate from other cephalosporins like cefazolin 6, 8
Rapid IV injection increases risk: The Iranian pharmacovigilance data identified rapid intravenous injection as a significant risk factor for severe adverse events, including 49 deaths attributed to ceftriaxone 9
Document permanently: This patient must have ceftriaxone (and potentially all cephalosporins) documented as a severe allergy, with prescription of an epinephrine autoinjector and referral to allergy/immunology 5
Do not rechallenge: The FDA label states "In case of severe hypersensitivity reactions, treatment with ceftriaxone must be discontinued immediately" and should never be restarted 1
Mortality risk: Ceftriaxone was responsible for the highest number of deaths in the Iranian pharmacovigilance database, with 30% of reported adverse events classified as serious, including cardiac arrest and anaphylaxis 9. This underscores the life-threatening nature of this reaction and the need for immediate, aggressive management.