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Use of Cephalosporin with Penicillin Hypersensitivity

Am Fam Physician. 2005 May 1;71(9):1794.

Penicillins are the most common cause of drug-induced, IgE-mediated hypersensitivity. Cephalosporin, which is a beta-lactam antibiotic like penicillin, can cause a similar reaction. Concern about the use of cephalosporins in patients who are allergic to penicillin has prompted the use of antibiotics that do not contain a beta-lactam ring. However, this may result in decreased efficacy, greater cost, and increased antimicrobial resistance. Skin tests can be used to identify IgE antibodies to penicillin. Patients with positive results are desensitized to cephalosporin or given an alternate drug. Currently, the best approach to patients with a reported history of penicillin allergy is uncertain. Romano and associates conducted a prospective study to evaluate the use of cephalosporins in volunteer patients allergic to penicillin.

Skin tests for three generations of cephalosporins were applied, and challenge doses of cefuroxime (500 mg orally) or ceftriaxone (1 g intramuscularly) were administered to patients with negative skin tests for all of the cephalosporins tested. Of the 128 patients who had a history of penicillin reaction and a positive result on penicillin skin testing, 14 (10.9 percent) had a positive skin test for cephalosporins. Ninety-four of the 114 (82.5 percent) patients who had negative skin tests to cephalosporins agreed to a challenge with cefuroxime and ceftriaxone. Of the nine patients who had positive skin reactions to a cephalosporin, seven patients accepted the challenge doses of a cephalosporin.

None of the volunteer patients experienced adverse reactions after the specific cephalosporin challenges. Cephalosporin skin tests at a concentration of 2 mg per mL seem to be reliable indicators of immediate hypersensitivity risk to cefuroxime and ceftriaxone. Of the three potential clinical options in the management of patients allergic to penicillin with compelling needs for cephalosporins, the authors recommend skin testing with cefuroxime or ceftriaxone (see accompanying table). If the testing is negative, a graded challenge is appropriate. Medicolegal issues may arise, however, because current practice guidelines recommend desensitization.

Clinical Options for Managing Patients with Penicillin Allergy Who Have a Compelling Need for Cephalosporins

Desensitize without cephalosporin testing. This option is supported by practice measures, but requires admission to the intensive care unit, delays reaching “full strength” antibiotic dose, and does not clarify whether patient is allergic to cephalosporins.

Graded cephalosporin challenge without skin testing. This option is safer than starting with a full dose, and a full dose can be reached within two hours. However, there is a medicolegal risk of reaction without desensitization effort, reaching “full strength” is delayed, and the question of cephalosporin allergy is not clarified.

Skin test with cefuroxime or ceftriaxone.* If negative, give a graded challenge of the tested cephalosporin. This option appears to be safe based on this study, avoids the need for admission to the intensive care unit, results in a shorter delay (i.e., two hours) to reaching full antibiotic strength, and clarifies the question of cephalosporin allergy. However, medicolegal issues remain if desensitization is not performed.


*—Recommended by the authors.

Clinical Options for Managing Patients with Penicillin Allergy Who Have a Compelling Need for Cephalosporins

View Table

Clinical Options for Managing Patients with Penicillin Allergy Who Have a Compelling Need for Cephalosporins

Desensitize without cephalosporin testing. This option is supported by practice measures, but requires admission to the intensive care unit, delays reaching “full strength” antibiotic dose, and does not clarify whether patient is allergic to cephalosporins.

Graded cephalosporin challenge without skin testing. This option is safer than starting with a full dose, and a full dose can be reached within two hours. However, there is a medicolegal risk of reaction without desensitization effort, reaching “full strength” is delayed, and the question of cephalosporin allergy is not clarified.

Skin test with cefuroxime or ceftriaxone.* If negative, give a graded challenge of the tested cephalosporin. This option appears to be safe based on this study, avoids the need for admission to the intensive care unit, results in a shorter delay (i.e., two hours) to reaching full antibiotic strength, and clarifies the question of cephalosporin allergy. However, medicolegal issues remain if desensitization is not performed.


*—Recommended by the authors.

Romano A, et al. Cross-reactivity and tolerability of cephalosporins in patients with immediate hypersensitivity to penicillins. Ann Intern Med. July 6, 2004;141:16–22.


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