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

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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Crossref · 10.1001/jama.2018.19283

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  • 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.

    “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]

  • Approximately 80% of patients with a true IgE-mediated allergic reaction to penicillin have lost the sensitivity after 10 years.

    “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]

  • 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.

    “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]

  • Allergic reactions with third-generation cephalosporins (e.g., ceftriaxone) are uncommon among persons with a history of penicillin allergy.

    “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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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
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 › 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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