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Am Fam Physician. 2002;65(1):109-114

Some patients with a self-reported history of penicillin allergy are limited from using drugs containing penicillin, even though their history may be vague and unconfirmed. Penicillin is withheld from many patients who could safely take the drug or its derivatives, causing increased health care costs and suboptimal prescribing. Results of studies have shown that 80 to 90 percent of patients who report a penicillin allergy are not actually allergic to the drug. Salkind and colleagues conducted a MEDLINE search to determine the likelihood that a patient has a true allergy to penicillin.

ReactionTime of onsetMediator(s)Clinical signsSkin testing useful?Comments
Immediate ¥(type 1)<One hour postexposurePenicillin-specific IgE antibodiesAnaphylaxis and/or hypotension, laryngeal edema, wheezing, angioedema, urticariaYesMuch more likely with parenteral administration than oral administration; fatal outcome in 1 per 50,000 to 1 per 100,000 treatment courses; some reactions occurring after one to 72 hours of exposure may be IgE mediated
Late>72 hours
Type IIIgG, complementIncreased clearance of red blood cells, platelets by lymphoreticular systemNoIgE not involved
Type IIIIgG, IgM immune complexesSerum sickness, tissue injuryNoTissue lodging of immune complexes; drug fever
Type IVContact dermatitisNo
Other (idiopathic)Usually >72 hours postexposureMaculopapular or morbilliform rashesNo1 % to 4 % of all patients receiving penicillin

The frequency of adverse reactions to penicillin among the general population ranges from 0.7 to 10 percent. This variation in the frequency of adverse reactions is caused by several factors, including exposure history, route of administration, duration of treatment, and time between initial reaction and subsequent reexposure. Allergic reactions to penicillin can be classified by length of time between exposure and onset of reaction or by type of reaction, immune mechanism, and clinical presentation (see accompanying table).

The history of the allergic reaction to penicillin should include the following questions: What was the patient's age at the time of the reaction? What were the characteristics of the reaction? How long after beginning penicillin therapy did the reaction begin? How was the penicillin administered? What other medications was the patient taking and at what time? What happened when the penicillin was discontinued? Has the patient taken any antibiotics similar to penicillin (i.e., amoxicillin, ampicillin, or cephalosporins) and, if so, what were the reactions? This detailed history will determine which patients have a true allergy to penicillin. Serious allergic or fatal reactions can occur in patients who have never had a previous allergic reaction to penicillin or have never been exposed to the medication.

Patients with a history of penicillin allergy and a positive skin test are more likely to also be allergic to cephalosporin antibiotics than patients with a history of penicillin allergy and a negative skin test (5.6 versus 1.7 percent, respectively). Some studies show that first-generation cephalosporins have a higher cross-reaction rate than newer cephalosporins, which may have been because some of them contained small amounts of penicillin. The authors advocate taking a detailed history before administering a cephalosporin to a patient with a history of penicillin allergy. If, based on a careful history, a true allergy seems unlikely, the cephalosporin can be administered. If an allergy seems likely, penicillin skin testing should be performed first. Penicillin skin testing should only be performed in patients with a clinical history of a type I penicillin allergy. Patients with a negative skin test can be given cephalosporin. If the skin test is positive and no other drug can be used, cephalosporin desensitization should be considered. Skin testing for cephalosporin is not useful because there is no standardization, and the negative predictive value of cephalosporin skin testing is unknown.

Patients who have a history of a type I allergic reaction to penicillin or who have a positive penicillin skin test should not be given carbapenems; however, aztreonam is almost universally safe in these patients. Penicillin is well-tolerated in 98 percent of patients with a positive history of a penicillin allergy and a negative skin test result.

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