Antibiotic Allergy Management

Classification and Reaction Timing

• The reaction can be classified based on timing and severity, with immediate reactions (<1 hour) including urticaria, angioedema, and anaphylaxis, accelerated reactions (1-72 hours) including urticaria and maculopapular rashes, and late reactions (>72 hours) including skin rashes and erythema multiforme 1

Management of Immediate-Type Reactions

• For immediate-type reactions, it is recommended to avoid all penicillins, avoid cephalosporins with similar side chains to the culprit penicillin, and consider monobactams and carbapenems as safe options 2

Management of Delayed-Type Reactions

• For delayed-type non-severe reactions, the American Academy of Allergy, Asthma, and Immunology recommends avoiding the culprit penicillin and those with similar side chains, using cephalosporins with dissimilar side chains, and considering monobactams and carbapenems as generally safe options 2
• Patients with a history of allergic reaction to penicillin that occurred less than 5 years ago should undergo skin testing before administering ureidopenicillins, especially if the reaction was confirmed by skin testing or was anaphylactic or severe, as recommended by the American Academy of Allergy, Asthma, and Immunology 2
• The skin test procedure should include major determinants (Penicilloyl-poly-lisina) and minor determinants (Penicillin G) to identify approximately 90-97% of allergic patients, with a sensitivity of 30.7% (95% CI: 18.9-45.9%) and a specificity of 96.8% (95% CI: 94.2-98.3%), as recommended by the CDC and the MMWR Recommendations and Reports guidelines 3, 4, 5, 6, 1
• Skin tests should be performed in a controlled environment where anaphylactic reactions can be treated, and patients should not have taken antihistamines recently before skin testing, as recommended by the American Academy of Allergy, Asthma, and Immunology 4

Antibiotic Cross-Reactivity

• The following antibiotics have been reported to have cross-reactivity with penicillins:

Risk Assessment and Testing

• Patients with a history of penicillin allergy who experienced reactions more than 5-10 years ago are considered low-risk for an allergic reaction, with a reported 95-98% of patients not experiencing reactions during the oral challenge, as recommended by the Clinical Microbiology and Infection guidelines 6, 1
• The PEN-FAST algorithm can be used to identify low-risk patients, assigning points for reaction timing, severity, and treatment required, with a score of <3 indicating low risk, and a diagnostic accuracy of moderate (statistic c: 0.686) 6, 1
• If skin tests are negative, ureidopenicillins could be administered with caution in a controlled environment, as recommended by the ESCMID 2
• If skin tests are positive, it is recommended to avoid all penicillins, including ureidopenicillins, or consider desensitization if they are absolutely necessary, as suggested by the CDC 3, 4

Treatment and Documentation

• Non-allergist physicians should have basic training in recognizing and treating anaphylaxis, as well as access to emergency medications (antihistamines and adrenaline), and adequate documentation in the electronic health record, as recommended by the Clinical Microbiology and Infection guidelines 1, 2
• The recommended protocol for non-allergist physicians includes administering 1/10 of the therapeutic dose (40-80 mg of amoxicillin) as the first dose, followed by observation for 30 minutes, then administering the full therapeutic dose (400-500 mg) and observing for an additional 60 minutes with vital sign monitoring, as recommended by the World Health Organization (WHO) 1
• Removing the penicillin allergy label allows for the use of first-line antibiotics (penicillins), reducing the use of broad-spectrum antibiotics and associated costs and side effects, as recommended by the Infectious Diseases Society of America 6, 1
• Approximately 10% of individuals who report having had severe allergic reactions to penicillin remain allergic over time, according to the Centers for Disease Control and Prevention (CDC) and supported by the MMWR Recommendations and Reports guidelines 3, 4, 5
• Even with negative tests, there is a small risk (3-10%) of allergic reactions in patients with true penicillin allergy, as tests without complete minor determinants may not detect all cases, as stated by the Clinical Microbiology and Infection guidelines 4, 5