Meropenem Does Not Require Skin Testing Before Administration
No skin test is needed before administering meropenem, even in patients with a history of penicillin or cephalosporin allergy. The 2022 American Academy of Allergy, Asthma, and Immunology guidelines explicitly state that carbapenems (including meropenem) may be administered without testing or additional precautions in patients with penicillin or cephalosporin allergy histories 1.
Evidence Supporting Direct Administration
Guideline Recommendations
The American Academy of Allergy, Asthma, and Immunology recommends that carbapenems can be given directly to patients with penicillin or cephalosporin allergy without prior skin testing (Conditional recommendation, Moderate certainty of evidence) 1.
This recommendation applies to all patients with penicillin or cephalosporin allergy histories, as long as the prior reaction was not a severe delayed cutaneous or organ-involved reaction (such as Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS syndrome) 1.
Cross-Reactivity Data
The evidence demonstrates exceptionally low cross-reactivity between carbapenems and other beta-lactams:
Cross-reactivity risk between carbapenems and penicillins is only 0.87% (95% CI: 0.32%-2.32%) based on a systematic review of 11 observational studies including 1,127 patients 1, 2.
Among 838 patients with proven, suspected, or possible IgE-mediated penicillin allergy, carbapenem reactions occurred in only 4.3% of patients (95% CI: 3.1%-5.9%) 1.
Of patients with positive penicillin skin tests (n=295), only 1 patient (0.3%; 95% CI: 0.06%-1.9%) had a reaction to carbapenem with symptoms consistent with a potentially IgE-mediated mechanism 1.
A prospective study of 211 patients with skin test-confirmed penicillin allergy demonstrated that all patients tolerated carbapenems without any reactions 1.
Real-World Clinical Experience
A prospective study of 110 patients with both non-anaphylactic (n=59) and anaphylactic (n=51) penicillin allergic reactions showed that all patients tolerated prolonged meropenem therapy (1-4 weeks) safely without any allergic reactions 3.
A retrospective analysis of 182 hospitalized patients with reported penicillin allergy who underwent bedside meropenem allergy assessment found that 196 diagnostic workups were performed with 189 (96.4%) being tolerated, and only 2 patients had mild, non-severe cutaneous reactions 4.
An Italian study of 104 patients with documented IgE-mediated penicillin hypersensitivity (positive skin tests) found that only 1 patient (0.9%; 95% CI: 0.02%-5.2%) had a positive intradermal test to meropenem, and all 103 patients with negative skin tests tolerated meropenem challenges 5.
When to Consider Additional Precautions
While skin testing is not required, certain clinical scenarios may warrant extra caution:
In patients with multiple drug allergies or significant patient anxiety, a graded drug challenge might be preferred over direct full-dose administration 1.
Patients with a history of severe delayed cutaneous reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis) or organ-involved reactions (DRESS syndrome, acute interstitial nephritis) to any beta-lactam should not receive carbapenems without specialist consultation 1.
Clinical Implementation
The practical approach is straightforward:
Administer meropenem directly at full therapeutic dose without preceding skin testing in patients with reported penicillin or cephalosporin allergy 1.
No allergy alert override is typically needed in electronic health records for carbapenem administration in penicillin-allergic patients 1.
Standard monitoring for any new antibiotic administration applies, but no special precautions beyond routine clinical care are necessary 3.
Important Caveats
The overall reported incidence of carbapenem allergy in the general population is only 0.3%-3.7%, making true carbapenem allergy rare 1.
This recommendation does not apply to patients with prior documented carbapenem allergy, who would require formal allergy evaluation before rechallenge 1.
The evidence supporting direct carbapenem administration is robust but comes primarily from observational studies, though the consistency across multiple studies and the prospective data strengthen confidence in this approach 1, 3, 4, 5.