Nafcillin hypersensitivity
Question:
6/10/2020
An 11 yo M presents for allergy testing. He has a history of systemic urticaria shortly after receiving his first dose of Nafcillin for osteomyelitis. No changes in LFTs or significant peripheral eosinophilia. Hives resolved in a couple of days on PO diphenhydramine. Naficillin's side R chain is not similar to other PO beta-lactams, of which I am aware. How would you go about skin testing and challenging as an outpatient?
Answer:
The history is consistent with a type I or IgE mediated allergic reaction. The possible antigenic determinants include the beta lactam nucleus or the side chains, but I would be most concerned about a response to the beta lactam. If nafcillin or another beta lactam antibiotic is the only antibiotic option based upon the culture and sensitivity of the organism, then I would skin test with penicillin G, major determinant (penicylloyl polylysine) and nafcillin 25 ug/ml (Table 18, p273.e51) by percutaneous and intradermal testing (1). Based upon the results of the testing, I would suggest a graded oral challenge (if the test were negative) or oral desensitization (if the test were positive), orally if possible or intravenously if an oral formulation of the desired antibiotic is not available. The reaction was not life-threatening but, if immunologically mediated, subsequent reactions may be more severe. There is a published cohort report of 467 nafcillin reactors who safely received a subsequent cephalosporin, but most of the preceding reactions in the cohort were not likely IgE mediated (2).
In summary, I would recommend an alternative antibiotic, ideally not a beta lactam, and would prefer the option of an oral challenge or desensitization with a related beta lactam if this class is required. If an oral formulation were not available, I would recommend hospitalization with IV challenge or desensitization. Skin testing with beta lactam antibiotics is recommended, and I would include nafcillin, acknowledging the positive and negative predictive value of nafcillin testing is not defined.
1. Solensky R, Khan DA et al. Drug allergy: an updated practice parameter. Ann Allergy Asthma Immunol 2010; 105:273e1- (https://www.aaaai.org/Aaaai/media/MediaLibrary/PDF%20Doceuments/Practice%20and%20Parameters/drug-allergy-updated-practice-param.pdf)
2. Blumenthal, Kimberly G., et al. "Tolerability of cefazolin after immune-mediated hypersensitivity reactions to nafcillin in the outpatient setting." Antimicrobial agents and chemotherapy 58.6 (2014): 3137-3143.
I hope this information is of help to you and your practice.
All my best.
Dennis K. Ledford, MD, FAAAAI