What is the concern with a penicillin allergy and the use of Zosyn (Piperacillin-Tazobactam)?

From the Guidelines

Patients with a penicillin allergy should generally avoid Zosyn (piperacillin-tazobactam) due to potential cross-reactivity, as the risk of cross-reactivity depends on the severity and nature of the original penicillin reaction, and alternative antibiotics from different classes may be considered depending on the infection being treated.

Key Considerations

• The risk of cross-reactivity between penicillins and cephalosporins is likely lower than previously thought, with some studies suggesting a cross-reactivity rate of less than 10% 1.
• For patients with severe penicillin allergies, such as anaphylaxis, angioedema, or Stevens-Johnson syndrome, Zosyn is contraindicated due to the potential for life-threatening reactions.
• For those with mild reactions, such as a non-itchy rash, the risk of cross-reactivity is lower but still present, and alternative antibiotics may be considered.
• Skin testing to confirm the allergy, graded challenge, or desensitization protocols under close medical supervision may be options if Zosyn is deemed medically necessary 1.

Alternative Antibiotics

• Fluoroquinolones, macrolides, or tetracyclines may be considered as alternative antibiotics depending on the infection being treated.
• The choice of alternative antibiotic should be based on the severity of the infection, the suspected or confirmed pathogen, and the patient's medical history and allergy profile.

Importance of Accurate Allergy Labeling

• Accurate labeling of penicillin allergy is crucial to ensure appropriate medication selection and monitoring, as an incorrect label can lead to the use of alternative antibiotics that may be less effective or have a higher risk of adverse reactions 1.
• A formal allergy history should be recorded in each patient reporting an antibiotic allergy to estimate the risk of recurrence and determine the best course of treatment.

From the Research

Penicillin Allergy and Zosyn

• Penicillin allergy is the most commonly reported antibiotic allergy, but most patients who report a positive history of a prior reaction to penicillin are not found to be allergic to penicillin upon skin testing 2.
• Zosyn, a combination of piperacillin and tazobactam, is a beta-lactam antibiotic that may be used as an alternative to penicillin in some cases.
• However, patients with a history of penicillin allergy may still be at risk for an allergic reaction to Zosyn, although the cross-reactivity between penicillin and cephalosporins, including Zosyn, is less common than previously thought 3.
• The mechanisms of antibiotic sensitization are not clearly understood, and desensitization protocols for cephalosporins, including Zosyn, are available but not standardized 2.
• Patients with a low-risk history of penicillin allergy may be evaluated with a direct amoxicillin challenge, while those with a moderate-risk history may be evaluated with penicillin skin testing 3.
• Penicillin skin testing, including skin testing and graded challenge, can help identify patients who are not allergic to penicillin and can safely receive Zosyn or other beta-lactam antibiotics 4, 5.
• The use of a penicillin allergy history algorithm and subsequent penicillin skin testing can be a safe and effective way to transition hospitalized patients from second-line to first-line antibiotic therapy, including Zosyn 5.
• It is essential to note that most beta-lactams, including Zosyn, may be safely used in penicillin-allergic patients, with the possible exception of first-generation and second-generation cephalosporins 4.