Is there cross-sensitivity between meropenem (a carbapenem antibiotic) and penicillin in patients with a known allergy to penicillin?

Cross-Sensitivity Between Meropenem and Penicillin

Meropenem can be safely administered to patients with penicillin allergy without prior testing or additional precautions, as cross-reactivity is extremely low (less than 1%). 1

Guideline-Based Recommendations

The 2022 Joint Task Force on Practice Parameters provides a conditional recommendation (with moderate certainty of evidence) that carbapenems, including meropenem, may be administered to patients with penicillin or cephalosporin allergy without testing or additional precautions. 1

Key Supporting Evidence

• The molecular structure of carbapenems is sufficiently dissimilar from penicillins, resulting in a very low risk of cross-allergy between these beta-lactam classes. 1

• A systematic review of 838 patients with proven, suspected, or possible IgE-mediated penicillin allergy found carbapenem reactions occurred in only 4.3% of patients overall, but among the subset with positive penicillin skin tests (n=295), only 1 patient (0.3%) had a potentially IgE-mediated reaction. 1

• A meta-analysis of 11 observational studies including 1,127 patients demonstrated a cross-reactivity risk to any carbapenem of only 0.87% (95% CI: 0.32%-2.32%). 1

• A prospective study of 211 patients with skin test-confirmed penicillin allergy demonstrated that all patients tolerated carbapenems without any reactions. 1

FDA Drug Label Considerations

The FDA label for meropenem includes important warnings but does not contraindicate use in penicillin-allergic patients: 2

• The label states that "there have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe hypersensitivity reactions when treated with another β-lactam," but this is a general precautionary statement applicable to all beta-lactams. 2

• Meropenem is contraindicated only 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-lactams." 2

• The key distinction is that this refers to documented meropenem or carbapenem allergy specifically, not penicillin allergy. 2

Clinical Application Algorithm

For patients with reported penicillin allergy requiring meropenem:

1. Administer meropenem without prior testing in the vast majority of cases, regardless of the severity or timing of the penicillin reaction. 1

2. Consider a graded drug challenge only in specific situations such as multiple drug allergies or significant patient anxiety, though this is not routinely necessary. 1

3. No skin testing is required before meropenem administration in penicillin-allergic patients. 1

Important Clinical Nuances

Why Cross-Reactivity is So Low

• Cross-reactivity between beta-lactams is primarily determined by R1 side chain similarity, not the shared beta-lactam ring structure. 1, 3

• Carbapenems have structurally distinct side chains compared to penicillins, which explains the negligible cross-reactivity rate. 1

Addressing Conflicting Evidence

While one older retrospective study from 2004 reported a higher cross-reactivity rate of 11% in penicillin-allergic patients, 4 this conflicts with more recent and higher-quality evidence:

• A 2008 prospective study of 110 patients with both non-anaphylactic and anaphylactic penicillin reactions showed zero allergic reactions to meropenem over 1-4 weeks of therapy. 5

• A 2023 bedside allergy assessment study of 182 hospitalized patients with penicillin allergy found that 96.4% tolerated meropenem, with only 2 patients experiencing non-severe cutaneous reactions. 6

• A pediatric study demonstrated only 0.9% cross-reactivity between penicillins and meropenem in children with documented IgE-mediated penicillin allergy. 7

The most recent and highest quality evidence (the 2022 practice parameter guideline) supersedes older observational data and supports safe administration without testing. 1

Common Pitfalls to Avoid

• Do not withhold meropenem based solely on penicillin allergy history, as this leads to use of less effective second-line antibiotics and contributes to antibiotic resistance. 6

• Do not confuse carbapenem cross-reactivity with cephalosporin cross-reactivity, which is higher (particularly for amino-cephalosporins with similar side chains at 12-16%). 1, 8

• Recognize that most reported "penicillin allergies" are not true IgE-mediated allergies (>95% are not true allergies), but even in confirmed penicillin allergy, meropenem remains safe. 9