I have been asked by my local hospital to comment on using Cefazolin or Cefuroxime for orthopedic patients with a history of penicillin allergy. The current use of Vancomycin is costly and time consuming. I have been sent numerous articles from the head pharmacist commenting on the lack of cross reactivity with these antibiotics based on side chains and the concern that reactions may be coincidental. Is there enough evidence to proceed with using either the first generation cephalosporin cefazolin or the second generation cefuroxime? Some of the articles I reviewed are by Pichicero (2005), Camapgna et al (2012), Apter et al (2006) and Macy. Thank you.


Thank you for your inquiry.

There is certainly a rationale to endorse the request of your head pharmacist. However, in my opinion, the evidence presented in the articles cited, although reassuring that routine administration of cephalosporins to a penicillin-allergic patient can usually be done without harm, this evidence is not definitive, and does not permit a “carte blanche” adherence to this policy. Perhaps the best way for you to respond to the request is to employ the Drug Allergy Parameters of the AAAAI and ACAAI via the Joint Council to craft your response. There is a detailed discussion of this issue and also an algorithm outlining a suggested approach.

I have also copied below some of the summary statements dealing with this issue, and as you can see, at least based upon my interpretation, one cannot make a definitive statement that all patients who have had a reaction to penicillin can take either a first or second generation cephalosporin without risks (even though the majority can do so).

On the website, you will find an excellent algorithm on Page 273.E46/274.E47 to help you craft your response. The algorithm gives you three options: consider skin testing to cephalosporins, penicillin skin testing, or “Give the cephalosporin directly (only in absence of severe and/or recent penicillin allergy reaction history). Although less than 1% will have a reaction within 24 hours, this is controversial as the reactions may be anaphylactic.”

In summary, I am in agreement with the statement quoted above, and I would suggest that you review the section in this parameter dealing with this issue in more depth, and write your response using this as a reference, and also employing the references supporting the stance established by this parameter.

Thank you again for your inquiry and we hope this response is helpful to you.

Drug Allergy: An Updated Practice; Chief Editors: Roland Solensky, MD, and David A. Khan, MD

Summary Statement 97:
Since 1980, studies show that approximately 2% of penicillin skin test–positive patients react to treatment with cephalosporins, but some of these reactions may be anaphylactic reactions. (C)

Summary Statement 98:
Without preceding penicillin skin testing, cephalosporin treatment of patients with a history of penicillin allergy, selecting out those with severe reaction histories, show a reaction rate of 0.1% based on recent studies. (C)

Summary Statement 99:
Penicillin skin testing, when available, should be considered before administration of cephalosporins in patients with a history of penicillin allergy. (E)

Summary Statement 100:
Patients who have a history of a possible IgE-mediated reaction to penicillin, regardless of the severity of the reaction, may receive cephalosporins with minimal concern about an immediate reaction if skin test results for penicillin major and minor determinants are negative. (B)

Summary Statement 101:
Treatment options for penicillin skin test–positive patients include (1) administration of an alternate (non beta lactam antibiotic, (2) administration of cephalosporin via graded challenge, or (3) administration of cephalosporin via rapid induction of drug tolerance. (E)

Summary Statement 102:
Skin testing to the cephalosporin followed by graded challenge appears to be a safe method for administration of some cephalosporins in penicillin allergic patients. (B)

Summary Statement 103:
If penicillin and cephalosporin skin testing is unavailable, depending on the reaction history, cephalosporins may need to be given via graded challenge or rapid induction of drug tolerance. (E)

Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology