Is Zosyn (piperacillin/tazobactam) safe to use in patients with a reported penicillin allergy manifested as a rash?

Zosyn Safety in Patients with Penicillin Allergy Manifested as Rash

Zosyn (piperacillin/tazobactam) is contraindicated in patients with a history of penicillin allergy manifested as a rash, as it is a penicillin-based antibiotic. 1

Understanding Penicillin Allergy and Cross-Reactivity

Penicillin allergies can be categorized based on severity and reaction type:

1. High-risk history: Includes patients with anaphylaxis, positive penicillin skin testing, recurrent penicillin reactions, or hypersensitivities to multiple β-lactam antibiotics 2

2. Moderate-risk history: Includes urticaria or other pruritic rashes and reactions with features of IgE-mediated reactions 2

3. Low-risk history: Includes isolated non-allergic symptoms, family history of penicillin allergy without personal history, pruritus without rash, or remote (>10 years) unknown reactions without IgE-mediated features 2

A rash in response to penicillin falls into the moderate-risk category, making Zosyn unsafe to use without further evaluation.

Alternative Antibiotic Options

For patients with penicillin allergy manifested as a rash, consider these alternatives:

Safe Alternatives with Minimal Cross-Reactivity:

• Aztreonam: Safe alternative with no cross-reactivity with penicillins (except potential cross-reactivity with ceftazidime) 3, 4

• Cefazolin: Has negligible cross-reactivity with penicillins and can be used regardless of severity or time since reaction 3

• Carbapenems: Can be safely administered without prior testing in penicillin-allergic patients 3

• Other cephalosporins with dissimilar side chains (e.g., cefpodoxime, ceftriaxone, ceftazidime, cefepime): Lower cross-reactivity rate of approximately 2.11% 3

Antibiotics to Avoid:

• Aminocephalosporins (e.g., cephalexin, cefadroxil): Higher cross-reactivity rate of 16.45% 3

• Cephalosporins with intermediate similarity scores (e.g., cefamandole): Cross-reactivity rate of 5.60% 3

Evaluation Before Antibiotic Selection

If Zosyn is strongly preferred for clinical reasons, consider:

1. Time since reaction: If the penicillin allergy (rash) occurred more than 5 years ago, the risk may be lower, but caution is still warranted 3

2. Penicillin skin testing: Carries a negative predictive value exceeding 95% and approaches 100% when combined with amoxicillin challenge 2

Clinical Decision Algorithm

1. Determine if Zosyn is absolutely necessary:

   • If no: Select an alternative antibiotic with minimal cross-reactivity (aztreonam, carbapenems)
   • If yes: Proceed to step 2

2. Assess time since reaction and severity:

   • If rash occurred within last 5 years: Avoid Zosyn
   • If rash occurred >5 years ago: Consider penicillin skin testing if available

3. If penicillin skin testing is available and negative:

   • Patient can likely receive Zosyn safely
   • Consider graded challenge or desensitization if testing is positive but Zosyn is essential

Important Caveats

• Although recent studies suggest lower cross-reactivity between penicillins and other β-lactams than previously thought 5, the FDA label explicitly contraindicates Zosyn in patients with penicillin allergy 1

• Many patients report penicillin allergies, but clinically significant IgE-mediated reactions are uncommon (<5%) 2

• Using broad-spectrum alternatives when not necessary can increase the risk of antimicrobial resistance and adverse events, including increased risk of MRSA, VRE, and C. difficile infections 2