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Evaluation and Management of Penicillin Allergy: A Review
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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In the citing paper
“Penicillin skin testing with a major determinant analog (penicilloyl-polylysine) and minor determinants (benzylpenicilloate, benzylpenilloate, or benzylpenicillin isomers of penicillin) are used for skin test evaluation for IgE-dependent penicillin allergy and can reliably identify persons at high risk for IgE-mediated reactions to penicillin (658,660,676).”
From Sexually Transmitted Infections Treatment Guidelines, 2021 (2021) · cites this paper as [658]
In the citing paper
“Approximately 80% of patients with a true IgE-mediated allergic reaction to penicillin have lost the sensitivity after 10 years (658).”
From Sexually Transmitted Infections Treatment Guidelines, 2021 (2021) · cites this paper as [658]
In the citing paper
“Prevalence of reported allergy to penicillin is approximately 10% among the U.S. population and higher among hospital inpatients and residents in health care–related facilities (655–658).”
From Sexually Transmitted Infections Treatment Guidelines, 2021 (2021) · cites this paper as [658]
In the citing paper
“Allergic reactions with third-generation cephalosporins (e.g., ceftriaxone) are uncommon among persons with a history of penicillin allergy (620,631,658,896).”
From Sexually Transmitted Infections Treatment Guidelines, 2021 (2021) · cites this paper as [658]
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Metadata
- 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)
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2019-01-15
- Volume
- 321
- Issue
- 2
- Pages
- 188
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- 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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