Robinson et al give a method for evaluating a patient with a history of reaction to a penicillin or other beta-lactam antibiotic. It is often possible to safely treat many patients with a history of penicillin allergy.


Step 1: Determine if the type of reaction was IgE-mediated or not.


Step 2: Determine its severity and if it was life threatening.


IgE mediated reactions include:

(1) urticarial rash

(2) diffuse erythema

(3) pruritis

(4) angioedema

(5) hyperperistalsis

(6) bronchospasm

(7) hypotension

(8) cardiac arrhythmia


If the patient has a vague or uncertain history of a rash, then assume that it was urticarial.


Do a skin test if the reaction was IgE-mediated and you plan to either:

(1) treat with a penicillin or carbapenem, OR

(2) treat with a cephalosporin and the previous reaction was life-threatening.


Skin testing should include all of the metabolites that could result in an allergic reaction.

(1) The major determinant for penicillin allergy is benzyl-penicilloyl-polylysine.

(2) Ideally other metabolites should be included for testing, but these may not be available or may be nonstandard.


If the skin test is positive, then either:

(1) avoid all beta-lactam agents

(2) desensitize the patient.


If the skin test is negative, then challenge with the intended agent.



• It is unclear how to approach the patient with a history of a non-life-threatening reaction for whom cephalosporin therapy is planned. I would think a challenge dose would be indicated.


Other Kind of Reaction



(1) nonurticarial skin rash

(2) fixed drug eruption

(3) toxic epidermal necrolysis or Stevens-Johnson syndrome

(4) serum sickness

(5) pulmonary infiltrate

(6) drug fever

(7) hematologic: hemolysis, thrombocytopenia, or neutropenia

(8) interstitial nephritis


If a non-IgE-mediated type of reaction occurred, then consider challenging with a penicillin, cephalosporin or carbapenem unless a potentially life-threatening reaction occurred.


Situations where a challenge should be avoided:

(1) If toxic epidermal necrolysis (TEN) or Stevens-Johnson (SJ) Syndrome, then skin testing should not be performed and penicillins should be avoided.

(2) I would think a history of interstitial nephritis might cause pause.


Drug Challenge


If the previous reaction was serious, then the challenge should be conducted in a supervised setting.



(1) Start with a small dose of an orally administered agent.

(2) If tolerated, then increase the dose of an orally administered agent.

(3) If tolerated, and if an intravenous route is anticipated, then try an intravenous dose.


Drugs to avoid in challenge testing and therapy:

(1) Avoid use of a first generation cephalosporin.

(2) Avoid use of cephamandole.


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