My patient has a penicillin allergy…what antibiotic do I choose?

Something like 10% of the US population reports an allergy to penicillin. However, as this CDC info sheet makes clear, <1% are truly allergic. That being said, if someone has ever had a reported reaction to a penicillin, think carefully before prescribing!

  1. Remind me what the penicillins are again? Obviously, anything with “penicillin” in the name (like penicillin G, benzathine penicillin), and derivatives like nafcillin, oxacillin, ampicillin, amoxicillin, and extended-spectrum forms like piperacillin and ticaricillin. The latter are important because they are found in medications like Zosyn and Unasyn which we typically think of as “big gun” antibiotics.
  2. Is it a true drug allergy? The difference between anaphylaxis and drug side effect can be life-saving. Allergy is an IgE-mediated reaction characterized by vasodilation (drop in blood pressure, flushing, tachycardia) and edema (wheezing, abdominal pain/gut edema) and in its most severe form, may cause anaphylactic shock. Hives are characteristic. On the other hand, side effects may be described as a “red rash,” nausea/diarrhea, dizziness, yeast infection. A family history of penicillin allergy doesn’t matter. Not discussed here are delayed allergic reactions, like SJS/TEN, serum sickness, DRESS, or other forms of organ damage. If someone has had a delayed reaction, they should never be given penicillins.
    • Questions to ask:
      • How quickly did your reaction happen? (Minutes, hours, days)
      • Did you have shortness of breath or swelling?
      • If there was a rash, was there blistering or peeling?
      • Did your doctors tell you there was organ damage? (liver, kidney dysfunction, changes in the blood counts, etc?)
  3. How long has it been since they took a penicillin? The data shows that over 80% of people who had a penicillin allergy 10 years ago won’t be allergic if they are given a penicillin drug again. Allergies change over the course of a person’s life, and sometimes what you were allergic to as a kid is no longer a problem.
  4. What are the risks of cross-sensitivity with cephalosporins and carbapenems? There is a reported 10% incidence of cross-sensitivity among penicillins, cephalosporins, and carbapenems (beta-lactam antibiotics). I found this review helpful in preparing this post, and one of the key takeaways is: “Persons who make IgE in response to cephalosporins seem to produce it only in response to a particular cephalosporin, whereas persons who make clinically significant IgE in response to penicillin tend to react to core penicillin break-down products.”
  5. What’s the deal with skin testing? Penicillin skin sensitivity testing is a critical tool for determining if someone is still at risk for an allergic reaction. It can be ordered for inpatients or outpatients, and can be done in conjunction with a pharmacist or allergist. If you are skeptical about the allergy (and brave) you can order a “test dose” or graded challenge of the medication, and if the patient tolerates it, put them on regular doses.
  6. I don’t have the time/energy to do skin testing, what can I use instead? People who are allergic to penicillin are more likely to have a reaction to a lower generation cephalosporin than higher generation. Cephalosporins to avoid: cephalexin, ceftriaxone, and cefpodoxime. Cefazolin and cefuroxime, because of their side chains, are less likely to react.  This review describes people who can be trialed on alternative beta-lactams and people who should continue to have complete avoidance. Going outside the beta-lactams, the world is your oyster: quinolones, vancomycin (or daptomycin), sulfa drugs (Bactrim), and aminoglycosides (gentamicin).



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