Results of the National Institute of Allergy and Infectious Diseases Collaborative Clinical Trial to test the predictive value of skin testing with major and minor penicillin derivatives in hospitalized adults.

BACKGROUND: A history (or lack thereof) of penicillin allergy is known to be unreliable in predicting reactions on subsequent administration of the drug. This study tests the usefulness of four penicillin allergen skin tests in the prediction of IgE-mediated reactions subsequent to administration of penicillin. METHODS: Eight centers cooperated in the National Institute of Allergy and Infectious Diseases trial of the predictive value of skin testing with major and minor penicillin derivatives. Hospitalized adults were tested with a major determinant (octa-benzylpenicilloyl-ocytalysine) and a minor determinant mixture and its components (potassium benzylpenicillin, benzylpenicilloate, and benzylpenicilloyl-N-propylamine). Patients then received a therapeutic course of penicillin and were observed, for 48 hours, for adverse reactions compatible with an IgE-mediated immediate or accelerated allergy. RESULTS: Among 726 history-positive patients, 566 with negative skin tests received penicillin and only seven (1.2%) had possibly IgE-mediated reactions. Among 600 history-negative patients, 568 with negative skin tests received penicillin and none had a reaction. Only nine of the 167 positive skin test reactors received a penicillin agent and then usually by cautious incremental dosing. Two (22%) of these nine patients had reactions compatible with IgE-mediated immediate or accelerated penicillin allergy; both were positive to the two determinants. CONCLUSIONS: These data corroborate previous data about the negative predictive value of negative skin tests to these materials. The reaction rate in skin test-positive patients was significantly higher than in those with negative skin tests, demonstrating the positive predictive value of positive tests to both major and minor determinants. The number of patients positive only to the major determinant or only to the minor determinant mix was too small to draw conclusions about the positive predictive value of either reagent alone.

Penicillin allergy.

Although many new antibiotics are available, penicillin and its many semisynthetic derivatives are first-line drugs for many infections. These agents are relatively nontoxic even at high doses; however, their use frequently leads to allergic reactions. Withholding penicillin therapy from patients at high risk of allergic reaction to it is the most effective means of preventing such occurrences. Because immunoglobulin E-mediated reactions account for significant mortality and morbidity in association with penicillin use, the thrust of research on penicillin allergy has been to prevent such reactions. The many risk factors associated with subsequent immunoglobulin E-mediated penicillin allergy include history, timing and nature of previous penicillin exposure and/or allergy, age, route of administration, and response to skin testing with major and minor determinants of penicillin. The relative predictive values of each are discussed. Cross-reactivity between penicillin and its many analogs is reviewed and an approach to the patient who has a positive history for penicillin allergy and is in need of penicillin is offered.

The atopic dog model: report of an attempt to establish a colony.

In an attempt to establish a colony of atopic dogs as a research resource, dogs with seasonal dermatitis - a reported manifestation of naturally occurring allergy in that species - were identified, acquired, and inbred. Progeny were studied during their first 2 years of life to determine if the trait could be genetically transmitted and to investigate the hypothesis that this spontaneously occurring dermatitis correlates with positive laboratory measurements for specific IgE to airborne allergens. (Serial immunoglobulin levels, including total IgE, end-point titration of histamine, and results of fecal examinations for identification of parasites were also investigated and are to be the subject of a separate publication.) Only a weak correlation between positive direct skin test results and the appearance of seasonal dermatitis was found in initial studies. Neither the results of testing by passive cutaneous anaphylaxis nor radioallergosorbent procedures correlated with positive clinical findings. Independently conducted clinical examinations and direct skin testing using selected antigens, as well as additional bronchial challenges of representative animals from the colony, also failed to furnish evidence of atopy in the dogs. Therefore, the goal of establishing an inbred line of atopic animals was not accomplished within the allotted 2-year period. Also, the data did not show a positive correlation between the seasonal dermatitis and measurements for specific IgE to airborne allergens.