Is there a cross-reactivity between Piperacillin/Tazobactam (Pip/Taz) and Penicillin allergy?

From the Guidelines

Piperacillin-tazobactam can be used with caution in patients with a history of penicillin allergy, as the cross-reactivity risk is low, ranging from 2.0% to 4.8% 1.

Key Considerations

• The cross-reactivity between penicillin and cephalosporins, including piperacillin-tazobactam, is largely due to the shared beta-lactam ring structure 1.
• Patients with a history of severe penicillin allergies, such as anaphylaxis, angioedema, respiratory distress, or hives, should be approached with caution when considering piperacillin-tazobactam therapy 1.
• For patients with mild penicillin allergies, such as rash only, piperacillin-tazobactam might be used with caution, preferably after allergy consultation or skin testing when possible 1.
• Alternative non-beta-lactam antibiotics, such as fluoroquinolones, aminoglycosides, or carbapenems, should be considered for patients with severe penicillin allergies or when piperacillin-tazobactam is not suitable 1.

Recommendations

• Piperacillin-tazobactam can be used in patients with a history of penicillin allergy, but with careful consideration of the patient's specific allergy history and severity 1.
• Patients with a suspected non-severe, delayed-type allergy to a cephalosporin can receive penicillins with dissimilar side chains, including piperacillin-tazobactam, irrespective of time since the index reaction 1.
• Aztreonam can be used in patients with a suspected immediate-type allergy to cephalosporins other than ceftazidime or cefiderocol, irrespective of severity and time since the index reaction 1.

Important Notes

• Always document the specific nature of the penicillin allergy in the patient's record to guide future antibiotic decisions and prevent unnecessary avoidance of effective treatments 1.
• Desensitization protocols performed under medical supervision may be considered when piperacillin-tazobactam must be used despite allergy concerns 1.

From the Research

Cross-Reactivity between Piperacillin/Tazobactam and Penicillin Allergy

• The study 2 found that one-third of patients were cross-sensitized to other penicillins, suggesting a potential cross-reactivity between Piperacillin/Tazobactam (Pip/Taz) and penicillin allergy.
• However, the same study also found that most patients (21 out of 48) were selectively sensitized to Pip/Taz and tolerated other penicillins, indicating that cross-reactivity may not be universal.
• Another study 3 reported that cross-reactivity between penicillin and cephalosporin drugs occurs in about 2% of cases, but did not specifically address Pip/Taz.
• A review of literature 4 found that the overall cross-reactivity rate between penicillins and cephalosporins is approximately 1% when using first-generation cephalosporins or cephalosporins with similar R1 side chains.
• A study on β-Lactam allergy and cross-reactivity 5 found that identities or similarities of β-lactam side-chain structures are mainly responsible for cross-reactivity among these antibiotics, but did not provide specific data on Pip/Taz and penicillin allergy.

Clinical Implications

• The study 2 suggests that patients with a history of penicillin allergy should be evaluated for cross-reactivity to Pip/Taz before administration.
• The review 3 recommends that clinicians evaluate penicillin allergy before deciding not to use penicillin or other β-lactam antibiotics, which may include Pip/Taz.
• The study 5 suggests that pre-treatment skin tests with related β-lactams are recommended before administering them via graded challenges to β-lactam-allergic patients who need alternative β-lactams, including Pip/Taz.