Penicillin allergy and the use of beta-lactam antibiotics

• In penicillin allergic patients, the incidence of allergic reactions to a cephalosporin was traditionally thought to be about 10-15%.
• However, new evidence suggests that the risk of cross-reactivity is actually much lower, less than 2%. Cross-reactivity between penicillins and cephalosporins is dependent on the side chain structure of the beta-lactam antibiotic (see Table 1).
• Cefazolin is not expected to cross-react with any penicillin or cephalosporin as it has unique side chains.
• First generation cephalosporins (but not cefazolin) with a side chain similar to penicillins have the highest potential for cross-reactivity, with an attributable risk of about 0.5%. Second- and third-generation cephalosporins have negligible risks of cross-reaction with penicillins.
• Data are lacking concerning cross-reactivity among beta-lactams with respect to delayed hypersensitivity reactions.

Recommendations for management (in the absence of diagnostic testing such as skin testing):

• In patients who do not have evidence of an immediate hypersensitivity reaction to a penicillin (i.e., delayed reaction or unknown reaction), any cephalosporin can be used.
• In patients who do have a history of an immediate hypersensitivity reaction to a penicillin, first-generation cephalosporins (notincluding cefazolin) and other penicillins should be avoided. However, non-cross-reactive second- or third generation cephalosporins (i.e., different side chains - see Table 1), cefazolin or carbapenems can be considered. Alternatively, if there is no suitable alternative antibiotic and a penicillin or a cephalosporin with a same/similar side chain is deemed necessary, the penicillin or cephalosporin may be used following successful desensitization.
• In patients with a history of a severe hypersensitivity reaction including severe cutaneous adverse reaction (e.g., SJS/TEN, DRESS), hemolytic anemia, an organ-specific reaction (e.g., acute interstitial nephritis), drug fever or serum sickness-like reaction to a specific beta-lactam, all beta-lactams should be avoided.

• The incidence of cross-reactions between penicillins and carbapenems is less than 1%.

Recommendations for management (in the absence of diagnostic testing such as skin testing):

• In patients who do not have evidence of an immediate hypersensitivity reaction to a penicillin (i.e., delayed reaction or unknown reaction), any carbapenem antibiotic can be used.
• In patients who do have a history of an immediate hypersensitivity reaction to a penicillin, carbapenems can be considered.
• In patients with a history of a severe hypersensitivity reaction including severe cutaneous adverse reaction (e.g., SJS/TEN, DRESS), hemolytic anemia, an organ-specific reaction (e.g., acute interstitial nephritis), drug fever or serum sickness-like reaction to a specific beta-lactam, all beta-lactams should be avoided.

• Even in patients with no penicillin allergy history, cephalosporins cause hypersensitivity reactions in 1-3% of patients.
• Clinical cross-reactivity among cephalosporins relates to side chain similarity (see Table 1). The “generation” a cephalosporin belongs to should not be used to predict cross-reactivity to other cephalosporins.

Recommendations for management (in the absence of diagnostic testing such as skin testing):

• In patients who do not have evidence of an immediate hypersensitivity reaction to a specific cephalosporin (i.e., delayed reaction or unknown reaction), any cephalosporin can be used, although avoidance of the specific cephalosporin that caused the reaction is suggested.
• In patients who do have a history of an immediate hypersensitivity reaction to a specific cephalosporin, a cephalosporin or penicillin with different side chain can be used. If there is no suitable alternative antibiotic and the culprit cephalosporin or one with a same/similar side chain is deemed necessary, the cephalosporin may be used following successful desensitization.
• In patients with a history of a severe hypersensitivity reaction including severe cutaneous adverse reaction (e.g., SJS/TEN, DRESS), hemolytic anemia, an organ-specific reaction (e.g., acute interstitial nephritis), drug fever or serum sickness-like reaction to a specific beta-lactam, all beta-lactams should be avoided.

• Beta-lactam allergy skin testing (BLAST) for select inpatients assessed by Infectious Diseases/Antimicrobial Stewardship teams is currently available on the inpatient units.
• BLAST can also be arranged in follow up from hospital in the Drug Safety Clinic. Referrals should be faxed to x 5229. More information is available at drugsafety.sunnybrook.ca
• For patients who are allergy test positive, desensitization is another alternative.Infectious Diseases and/or Clinical Pharmacology should be consulted to assess therapeutic alternatives and to arrange for desensitization if appropriate.

There is no evidence that IgE-mediated reactions are genetically mediated.Therefore, a history of penicillin allergy in one family member is not a contraindication to the use of a penicillin for another family member.