Is ertapenem (a carbapenem antibiotic) safe to use in patients with a penicillin allergy?

Ertapenem Safety in Patients with Penicillin Allergy

Ertapenem can be safely administered to patients with penicillin allergy, irrespective of severity or time since the index reaction, without prior allergy testing. 1

Cross-reactivity Between Penicillins and Carbapenems

The risk of cross-reactivity between penicillins and carbapenems is very low due to key structural differences:

• Carbapenems have molecular structures sufficiently dissimilar from penicillins, resulting in a very low risk of cross-allergy 1
• The meta-analysis by Picard et al. (2019) demonstrated that carbapenems can be administered without prior testing in both severe and non-severe immediate-type penicillin allergies 1
• The risk of cross-reactivity between penicillins and any carbapenem is only 0.87% (95% CI: 0.32%-2.32%) 1

Clinical Recommendations for Ertapenem Use in Penicillin-Allergic Patients

For Immediate-Type Penicillin Allergy:

• Ertapenem can be administered without prior allergy testing, regardless of:
  • Severity of the previous reaction 1
  • Time elapsed since the index reaction 1
  • Whether the allergy is confirmed or suspected 1

For Delayed-Type Penicillin Allergy:

• Patients with non-severe, delayed-type penicillin allergy can receive any carbapenem, including ertapenem, without prior allergy testing 1
• This recommendation applies regardless of when the index reaction occurred 1

FDA Labeling Considerations

While the FDA label for ertapenem includes standard warnings about hypersensitivity reactions:

• It states that "serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving therapy with beta-lactams" 2
• The label recommends "careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, other beta-lactams and other allergens" 2

However, these are standard warnings for all beta-lactams and should be interpreted in light of the more recent clinical evidence showing very low cross-reactivity.

Clinical Evidence Supporting Safety

• In a study of 49 patients with confirmed IgE-mediated β-lactam allergy, 35 of 36 patients who underwent challenges tolerated the full dose of ertapenem 3
• Another study showed only 0.9% cross-reactivity between penicillins and meropenem (another carbapenem) 4
• The practice of routinely avoiding carbapenems in patients with penicillin allergy should be abandoned given the very low cross-reactivity rates 3, 5

Practical Approach

For patients with penicillin allergy requiring ertapenem:

1. Document the nature of the previous reaction (immediate vs. delayed, severe vs. non-severe)
2. Proceed with ertapenem administration without prior testing 1
3. As with any medication, monitor for potential hypersensitivity reactions, especially during the first administration 2
4. If there are specific concerns about a severe previous reaction, consider administering the first dose in a monitored setting, though this is not specifically required by guidelines 1

Common Pitfalls to Avoid

• Unnecessarily avoiding ertapenem in penicillin-allergic patients, which may lead to use of less effective or more toxic alternatives 5
• Assuming high cross-reactivity between penicillins and carbapenems based on older literature 6
• Failing to distinguish between true allergic reactions and other adverse effects when evaluating penicillin "allergy" 5

The evidence strongly supports that ertapenem can be safely used in patients with penicillin allergy, with the very low risk of cross-reactivity not warranting routine avoidance or prior testing.