Ask the Expert January/February
Joel Schofer, MD
LCDR MC USN, Naval Hospital
“Ask The Expert” is a Common Sense feature where subject matter experts provide answers to questions provided by YPS members. This edition features Dr. Jonathan Davis, who presented “An Evidence Based Medicine Approach to Anaphylaxis” at the AAEM 2007 Scientific Assembly.
Question:
Can you give a cephalosporin to a patient who is allergic to penicillins and only had a nonspecific rash as his/her reaction? What if he/she had urticaria instead of a non-specific rash?
Answer:
A great deal of confusion persists among healthcare providers regarding the use of cephalosporins in patients with a history of penicillin allergy. The best approach to this clinical conundrum first involves asking two critical questions:
1. Is a patient with a stated “penicillin allergy” actually allergic to penicillin in the first place?
2. If it is indeed a legitimate penicillin allergy, what is the potential for anaphylaxis when administering a cephalosporin?
Allergic emergencies can present with a variety of clinical manifestations, ranging from isolated skin findings (flushing, urticaria, angioedema) to respiratory failure and cardiovascular collapse. Allergic emergencies typically involve IgE antibodies (Gell and Coombs Type I, immediate hypersensitivity reactions). Much of the confusion regarding a “penicillin allergy” stems from the blurred distinction between a prior true drug allergy (Type I hypersensitivity reaction) and a non-IgE-mediated adverse drug event (vomiting, lightheadedness, diarrhea, non-specific rash). Indeed, older reports have indicated that fewer than 10% of patients claiming to have a “penicillin allergy” actually have Type I hypersensitivity to penicillin. The majority of patients with a stated “penicillin allergy” are not at risk for immediate hypersensitivity reactions to penicillins.
In the case of a legitimate penicillin allergy, what is the potential for anaphylaxis when administering a cephalosporin? The widely cited figure of “10% cross-reactivity” appears to come from seminal data examining the incidence of early 1st-generation cephalosporin reactions. However, it was later found that these early 1st-generation agents contained trace amounts of penicillin, as they were derived from the same mold.
More recent findings suggest that 1st-generation cephalosporins may pose a greater risk in penicillin-sensitive patients as compared with either 2nd- or 3rd-generation agents. However, the risk of 1st-generation agents is still minimal. A review in 2001 estimated a 4.4% cross reactivity rate based on skin testing, although the clinical relevance of this rate remains unclear. Interestingly, the latest evidence suggests that the immune response to cephalosporins may be more dependent on specific side-chain components, as opposed to their beta lactam ring structure.
Clearly, what we are most concerned about as practitioners is the potential for an IgE-mediated, immediate hypersensitivity reaction, and its associated morbidity and potential for fatal outcome. When combining the available data, the risk of 2nd- or 3rd-generation cephalosporins in “penicillin allergic” patients is minimal (less than 1%). When compared with an overall incidence of antimicrobial hypersensitivity in general (1 to 3%), there is no additional risk of 2nd- or 3rd-generation agents over alternative antimicrobials.
So, in a nutshell, patients with a history of a non-specific rash following penicillin administration have more than likely suffered a non-IgE-mediated response, and are not at increased risk for allergic emergencies resulting from members of the penicillin or cephalosporin families. In the case of an urticarial reaction (which may be the mildest variant on the spectrum of IgE-mediated symptoms), penicillins and perhaps 1st-generation cephalosporins should be avoided (although the risk of 1st-generation agents is still minimal). However, the risk of cross-reactivity to a 2nd- or 3rd-generation agent is no more likely than a reaction to any administered antimicrobial, irrespective of drug family.
Reference:
Pichichero ME. Cephalosporins can be prescribed safely for penicillin-allergic patients. J Fam Pract. 2006 Feb;55(2):106-12.
Jonathan Davis, MD FAAEM
Associate Program Director, Assistant Professor
If you have a question that you would like to have answered by an expert in a future issue of Common Sense, please send it to jschofer@gmail.com.
The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the U.S. Government.