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Penicillin Allergy

Some Simple Facts

  • Penicillin (examples: ampicillin, amoxicillin, Pen VK) is the most common cause of allergic drug reactions.
  • Reactions can vary from rashes (hives), fevers, acute kidney disease, and lung infiltrates (pneumonias) to life-threatening widespread eruptions (Stevens-Johnson Syndrome).
  • Some reactions, after ingestions of ampicillin and amoxicillin most often, are not caused by an allergic mechanism. These reactions are generally non-pruritic (non-itchy) and associated with viral infections like mononucleosis.
  • Anaphylaxis occurs roughly in 1-4 patients for every 10,000 treated patients, but penicillin-induced anaphylaxis is the most common cause of death from anaphylaxis.
  • Most often occurs in adults between the ages of 20-49.
  • Most fatal reactions occur in patients with no history of penicillin allergy.

Penicillin drugs cause allergic reactions by binding of proteins to IgE antibodies. The reactions are produced by the breakdown or metabolism products of penicillin and they are given names:

  • The “major-determinant” (benzlypenicilloyl) causes most (95%) of the allergic reaction. This molecule is commercially produced as a penicilloyl polylysine molecule (PPL) also known as Pre-Pen.
  • There are also “minor-determinants” as well which are produced when penicillin is metabolized (acid and alkaline breakdown products of penicillin).

Skin testing is the most accurate way to test for an allergy, but testing needs to be done by a specialist that understands how to properly test and uses the correct materials.

  • Skin testing can test for allergies to these major and minor Penicillin proteins.
  • If just Pre-Pen and a solution of Penicillin G from a pharmacy are used for testing, you will miss 5-10% of positive reactions. Some of these persons that are missed are at risk for life-threatening, anaphylactic reactions.
  • If Pre-pen and a mixture of minor determinants (which are not commercially available) are used as testing materials, only a small percentage of patients (0.5% to 3%) have adverse reactions (allergic reactions). None of these reactions have been reported to be life threatening.

If after negative skin testing for Penicillin allergy, does that mean that you are okay to take any of penicillins (such as Dicloxacillin or piperacillin)?

  • The simple answer is NO. While significant cross-reactivity occurs (patients allergic to Penicillin are allergic to all drugs of that class), a NEGATIVE skin test for Penicillin does not rule out a reaction to some of the newer (semi-synthetic) penicillins. After reactions to these newer drugs, patients may require specific testing for that particular medicine.
  • Cephalosporins (such as Keflex) are known to cross-react with Penicillin because they have a similar ring structure. Data from the literature suggests that 10% of patients with Penicillin allergy also have a cephalosporin allergy. So care must be taken when placing patients on cephalosporins when there is a history of severe allergies to Penicillin.
  • Blood tests (RAST and ELISA) can detect IgE antibodies to the major determinant, but the clinical usefulness is limited. If you do have a blood test positive for PPL (major determinant), you should be considered at risk for a reaction.

What happens if you need to take a Penicillin drug?

  • First, consider safe unrelated alternatives.
  • If there are no safe alternatives, than desensitization protocol, usually preformed in a hospital setting can be done. The drug is administered over hours to days, which results in a patient converting from a “drug-sensitive” state to a tolerant state.
  • Desensitization is only effective for the one particular episode and if you later need to take Penicillin, desensitization needs to be done again.
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