Evaluation and Management of Penicillin Allergy: A Review

JAMA. 2019 Jan 15;321(2):188-199. doi: 10.1001/jama.2018.19283.

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.

Publication types

  • Review

MeSH terms

  • Amoxicillin / adverse effects
  • Amoxicillin / therapeutic use
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / immunology
  • Anti-Bacterial Agents / therapeutic use
  • Desensitization, Immunologic
  • Drug Hypersensitivity / diagnosis*
  • Drug Hypersensitivity / immunology
  • Drug Hypersensitivity / therapy
  • Female
  • Humans
  • Immunoglobulin E
  • Immunologic Tests*
  • Patient Acuity
  • Penicillins / adverse effects*
  • Penicillins / immunology
  • Penicillins / therapeutic use
  • Pregnancy
  • beta-Lactams / adverse effects
  • beta-Lactams / immunology

Substances

  • Anti-Bacterial Agents
  • Penicillins
  • beta-Lactams
  • Immunoglobulin E
  • Amoxicillin