The rational clinical examination. Is this patient allergic to penicillin? An evidence-based analysis of the likelihood of penicillin allergy

JAMA. 2001 May 16;285(19):2498-505. doi: 10.1001/jama.285.19.2498.


Context: Clinicians frequently withhold antibiotics that contain penicillin based on patients' self-reported clinical history of an adverse reaction to penicillin and the clinicians' own misunderstandings about the characteristics of a true penicillin allergy.

Objectives: To determine the likelihood of true penicillin allergy with consideration of clinical history and to evaluate the diagnostic value added by appropriate skin testing.

Data sources: MEDLINE was searched for relevant English-language articles dated 1966 to October 2000. Bibliographies were searched to identify additional articles.

Study selection: We included original studies describing the precision of skin testing in diagnosis of penicillin allergy. We excluded studies that did not use both minor and major determinants, provide an explicit definition of penicillin allergy, or list the specific criteria necessary for a positive skin test result. Fourteen studies met the inclusion criteria.

Data extraction: Three authors independently reviewed and abstracted data from all articles and reached consensus about any discrepancies.

Data synthesis: Patients' self-reported history has low accuracy for diagnosis of true penicillin allergy. By evaluating studies comparing clinical history to the skin test for penicillin allergy among patients with and without a positive history for penicillin allergy, positive and negative likelihood ratios were calculated. History of penicillin allergy had a positive likelihood ratio of 1.9 (95% confidence interval [CI], 1.5-2.5), while absence of history of penicillin allergy had a negative likelihood ratio of 0.5 (95% CI, 0.4-0.6).

Conclusions: Only 10% to 20% of patients reporting a history of penicillin allergy are truly allergic when assessed by skin testing. Taking a detailed history of a patient's reaction to penicillin may allow clinicians to exclude true penicillin allergy, allowing these patients to receive penicillin. Patients with a concerning history of type I penicillin allergy who have a compelling need for a drug containing penicillin should undergo skin testing. Virtually all patients with a negative skin test result can take penicillin without serious sequelae.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cephalosporins / adverse effects
  • Cephalosporins / immunology
  • Decision Making
  • Drug Hypersensitivity / diagnosis*
  • Humans
  • Medical History Taking
  • Penicillins / adverse effects*
  • Penicillins / immunology
  • Penicillins / therapeutic use
  • Probability
  • Skin Tests


  • Cephalosporins
  • Penicillins