Cited by 831Drug-Induced Adverse ReactionsPharmacovigilance and Adverse Drug ReactionsFood Allergy and Anaphylaxis Research

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Evaluation and Management of Penicillin Allergy: A Review

Shenoy, Erica S., Macy, Eric, Rowe, Theresa, Blumenthal, Kimberly G.·2019·JAMA

DOI 10.1001/jama.2018.19283

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Abstract

IMPORTANCE: β-Lactam antibiotics are among the safest and most effective antibiotics. Many patients report allergies to these drugs that limit their use, resulting in the use of broad-spectrum antibiotics that increase the risk for antimicrobial resistance and adverse events. OBSERVATIONS: Approximately 10% of the US population has reported allergies to the β-lactam agent penicillin, with higher rates reported by older and hospitalized patients. Although many patients report that they are allergic to penicillin, clinically significant IgE-mediated or T lymphocyte-mediated penicillin hypersensitivity is uncommon (<5%). Currently, the rate of IgE-mediated penicillin allergies is decreasing, potentially due to a decreased use of parenteral penicillins, and because severe anaphylactic reactions to oral amoxicillin are rare. IgE-mediated penicillin allergy wanes over time, with 80% of patients becoming tolerant after a decade. Cross-reactivity between penicillin and cephalosporin drugs occurs in about 2% of cases, less than the 8% reported previously. Some patients have a medical history that suggests they are at a low risk for developing an allergic reaction to penicillin. Low-risk histories include patients having isolated nonallergic symptoms, such as gastrointestinal symptoms, or patients solely with a family history of a penicillin allergy, symptoms of pruritus without rash, or remote (>10 years) unknown reactions without features suggestive of an IgE-mediated reaction. A moderate-risk history includes urticaria or other pruritic rashes and reactions with features of IgE-mediated reactions. A high-risk history includes patients who have had anaphylaxis, positive penicillin skin testing, recurrent penicillin reactions, or hypersensitivities to multiple β-lactam antibiotics. The goals of antimicrobial stewardship are undermined when reported allergy to penicillin leads to the use of broad-spectrum antibiotics that increase the risk for antimicrobial resistance, including increased risk of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. Broad-spectrum antimicrobial agents also increase the risk of developing Clostridium difficile (also known as Clostridioides difficile) infection. Direct amoxicillin challenge is appropriate for patients with low-risk allergy histories. Moderate-risk patients can be evaluated with penicillin skin testing, which carries a negative predictive value that exceeds 95% and approaches 100% when combined with amoxicillin challenge. Clinicians performing penicillin allergy evaluation need to identify what methods are supported by their available resources. CONCLUSIONS AND RELEVANCE: Many patients report they are allergic to penicillin but few have clinically significant reactions. Evaluation of penicillin allergy before deciding not to use penicillin or other β-lactam antibiotics is an important tool for antimicrobial stewardship.

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Authors: Shenoy, E. S., Macy, E., Rowe, T., & Blumenthal, K. G.
Affiliations: Harvard University (US)
Department of Allergy, Southern California Permanente Medical Group, San Diego Medical Center
Northwestern University (US)
ORCID: Shenoy, Erica S.
Macy, Eric
Rowe, Theresa
Blumenthal, Kimberly G.
Venue: JAMA
Publisher: American Medical Association (AMA)
Published: 2019-01-15
Volume: 321
Issue: 2
Pages: 188
ISSN: 0002-9955 (ISSN-L)
0098-7484
DOI: 10.1001/jama.2018.19283
OpenAlex: W2909667144
Cited by: 830
References: 116
Citations by year: 2026: 109 · 2025: 120 · 2024: 130 · 2023: 132 · 2022: 100 · 2021: 90 · 2020: 89 · 2019: 58
FWCI: 10.82
Type: journal article
Language: en
Open access: closed
Locations: JAMA (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Drug-Induced Adverse Reactions
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
Health Sciences › Medicine › Immunology and Allergy › Food Allergy and Anaphylaxis Research
Keywords: penicillin allergy, beta-lactam antibiotics, IgE-mediated hypersensitivity, penicillin skin testing, antimicrobial stewardship, broad-spectrum antibiotic use, antimicrobial resistance, Clostridium difficile infection, methicillin-resistant Staphylococcus aureus
MeSH terms: Amoxicillin, Anti-Bacterial Agents, Desensitization, Immunologic, Drug Hypersensitivity, Female, Humans, Immunoglobulin E, Immunologic Tests, Penicillins, Pregnancy, beta-Lactams, Patient Acuity

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Evaluation and Management of Penicillin Allergy: A Review

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