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Cephalosporins in Patients with Penicillin Allergy: Use Them . . . but Be Careful

Patients with penicillin allergy are not necessarily allergic to cephalosporins.

Use of cephalosporins for treatment of pediatric infections is limited because of concern about cross-reactivity in patients with penicillin allergy. In an industry-supported review, researchers examined the evidence from 44 studies on cephalosporin cross-reactivity in patients allergic to penicillin (J Am Pharm Assoc 2008; 48:530).

About 10% of patients in the general population report allergic responses to penicillin and the reported risk for anaphylactic reaction to cephalosporins ranges from 1:1000 to 1:1,000,000, but this risk is increased fourfold in patients with penicillin allergy. Characteristics of adverse drug reactions (immunologic, nonimmunologic, duration, severity) are key to distinguishing allergic from nonallergic adverse reactions. The reported frequency of cross-reactivity between cephalosporins and penicillin is 7% to 18%, but the authors cite recent data that suggest that the incidence of true allergic reactions is lower because much of the evidence was based on nonallergic adverse reactions or in vitro studies, rather than on clinically relevant immune-mediated reactions. Further, improved manufacturing processes have removed contaminants from penicillins and cephalosporins that might have caused cross-reactivity reactions. First-generation cephalosporins are associated with higher risk for cross-reactivity than later-generation agents due to changes in the chemical structure.

Clear contraindications to use of cephalosporins include history of penicillin-associated type I anaphylaxis reactions associated with the presence of IgE antibodies, Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema, interstitial nephritis, vasculitis, serum sickness, hemolytic anemia, neutropenia, and thrombocytopenia.

Comment: The good news is that patients with penicillin allergy are not necessarily allergic to cephalosporins. The bad news is that some cross-reactivity exists. Clinicians need to evaluate risk based on history and diagnostic testing. The most important factors to assess when considering the use of cephalosporins in penicillin-allergic patients is the nature and extent of previous allergic reactions and the type of cephalosporin to be used. When cephalosporin use is necessary in life-threatening situations, skin testing and drug-challenge desensitization might be appropriate. Fortunately, the risk for cross-reactivity with third- and fourth-generation cephalosporins is very low, and reasonable treatment alternatives exist.

— William P. Kanto, Jr., MD

Published in Journal Watch Pediatrics and Adolescent Medicine May 27, 2009

Reader Remarks:

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• cross sensitivity
  R H Schneider, 28 May 2009 12:58 PM EST
  Have used cephalosporins in pts "said" to have pen allergy. No observed reaction in >40 yrs. Luck? Reactions rarer than... [more]
• role of montleukast in stevens-johonson reaction
  Maged A. Zaki, Student's Hospital, HIO, Alexandria ,Egypt, 8 Jun 2009 1:12 PM EST
  In 2 cases of stevens- johnson reaction due to phenitoin in pediatric age , I used montleukastin (antileukotrien) in addition... [more]
• cephalosporin and pcn reactions
  A. Pennisson,MD, 9 Jun 2009 12:33 PM EST
  Same here - no reactions in 20 years with cephalosporins in those with pcn reactions. I do not use in... [more]