What is the degree of cross-reactivity between meropenem and penicillin allergy?

Meropenem Cross-Reactivity with Penicillin Allergy

Meropenem can be safely administered to patients with penicillin allergy without prior testing, as the cross-reactivity risk is extremely low at approximately 0.9% (95% CI: 0.32%-2.32%).

Cross-Reactivity Risk Assessment

Carbapenems like meropenem have molecular structures sufficiently dissimilar from penicillins, resulting in minimal cross-reactivity:

• The risk of cross-reactivity between penicillins and meropenem is approximately 0.9% (95% CI: 0.32%-2.32%) based on meta-analysis data 1
• A prospective study of 211 patients with skin test-confirmed penicillin allergy demonstrated that all tolerated carbapenems 1
• In a clinical study of 110 patients with reported penicillin allergies (including 51 with anaphylactic reactions), none experienced allergic reactions when given meropenem 2
• Another study found only 1 out of 104 patients (0.9%) with documented penicillin allergy had a positive skin test to meropenem, while the remaining 103 tolerated meropenem challenges 3

Clinical Recommendations

For Immediate-Type (IgE-Mediated) Penicillin Allergy:

• Meropenem can be administered without prior allergy testing, regardless of severity or time since the initial reaction 1
• The practice of avoiding meropenem in penicillin-allergic patients should be reconsidered due to the low cross-reactivity 3

For Delayed-Type Penicillin Allergy:

• Meropenem can be administered without prior testing in patients with non-severe delayed-type reactions 1
• Exception: Avoid meropenem in patients with history of severe cutaneous adverse reactions (SCARs) to penicillins, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS 4, 5

Important Considerations

1. FDA Label Warning: The meropenem FDA label states that it is "contraindicated in patients with known hypersensitivity to any component of this product or to other drugs in the same class or in patients who have demonstrated anaphylactic reactions to beta(β)-lactams" 5. However, recent clinical evidence and guidelines suggest this warning may be overly cautious.

2. Special Populations:

   • Children with IgE-mediated penicillin hypersensitivity show similarly low cross-reactivity rates (0.9%) 6
   • The safety profile is consistent across adult and pediatric populations

3. Monitoring:

   • Despite the low risk, patients receiving their first dose of meropenem should be observed for 30-60 minutes after administration 7
   • Healthcare providers should be prepared to manage allergic reactions in the rare event they occur

Conclusion

The evidence strongly supports that meropenem can be safely administered to patients with penicillin allergy without prior testing, with the exception of those with history of severe cutaneous adverse reactions to beta-lactams. The cross-reactivity risk is minimal (approximately 0.9%) and significantly lower than previously assumed.