Is it safe to administer meropenem to a patient with a hypersensitivity reaction to penicillin (antibiotic)?

From the Guidelines

Meropenem can be used in patients with a suspected immediate-type allergy to penicillin, as the risk of cross-reactivity is considered low, according to the most recent guideline from the Dutch Working Party on Antibiotic Policy (SWAB) published in 2023 1. The guideline suggests that any carbapenem, including meropenem, can be used in a clinical setting in patients with suspected immediate-type allergy to a cephalosporin, irrespective of severity or time since the index reaction. Although this specific recommendation is for cephalosporin allergies, the principle can be applied to penicillin allergies due to the shared beta-lactam ring structure but distinct side chains that reduce cross-reactivity. Key considerations include:

• The severity of the previous allergic reaction to penicillin
• The time elapsed since the last reaction
• The availability of alternative antibiotics
• The necessity of using meropenem for the patient's condition Given the low quality of evidence for some recommendations, a cautious approach is advised, especially in patients with a history of severe allergic reactions. In clinical practice, meropenem should be administered with careful monitoring, especially in patients with a history of severe penicillin allergy, and desensitization protocols may be considered if meropenem is deemed essential for a patient with a severe penicillin allergy. The decision should be made on a case-by-case basis, considering the potential benefits and risks of using meropenem in patients allergic to penicillin, as suggested by the guideline 1.

From the FDA Drug Label

5 WARNINGS AND PRECAUTIONS

1. 1 Hypersensitivity Reactions Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving therapy with β-lactams. These reactions are more likely to occur in individuals with a history of sensitivity to multiple allergens There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe hypersensitivity reactions when treated with another β-lactam. Before initiating therapy with meropenem for injection, it is important to inquire about previous hypersensitivity reactions to penicillins, cephalosporins, other β-lactams, and other allergens.

Caution is advised when administering meropenem to a patient allergic to penicillin, as there have been reports of severe hypersensitivity reactions in individuals with a history of penicillin hypersensitivity when treated with another β-lactam, including meropenem 2.

• It is essential to inquire about previous hypersensitivity reactions to penicillins, cephalosporins, other β-lactams, and other allergens before initiating therapy with meropenem.
• If an allergic reaction to meropenem occurs, the drug should be discontinued immediately. Meropenem should be used with caution in patients with a history of penicillin allergy.

From the Research

Meropenem Administration in Penicillin-Allergic Patients

• Meropenem can be safely administered to patients with a reported penicillin allergy, including those with anaphylactic reactions, without penicillin skin testing 3.
• A study found that 110 patients with non-anaphylactic and anaphylactic penicillin allergic reactions tolerated prolonged meropenem therapy safely without any allergic reactions 3.
• The cross-reactivity between penicillin and meropenem is low, and meropenem may be given to patients with known or unknown allergic reactions to penicillin 3.

Penicillin Allergy and Cross-Reactivity

• Approximately 10% of the US population reports an allergy to penicillin, but clinically significant IgE-mediated or T lymphocyte-mediated penicillin hypersensitivity is uncommon (<5%) 4.
• Cross-reactivity between penicillin and cephalosporin drugs occurs in about 2% of cases, and the rate of IgE-mediated penicillin allergies is decreasing 4.
• The mechanisms of antibiotic sensitization are not clearly understood, and avoidance of cephalosporins may be recommended in cases of penicillin allergy, but newer generation cephalosporins have demonstrated less cross-reactivity to penicillin than earlier generation ones 5, 6.

Meropenem and Cephalosporin Use in Penicillin-Allergic Patients

• The use of third- or fourth-generation cephalosporins or cephalosporins with dissimilar side chains than the offending penicillin carries a negligible risk of cross allergy 6.
• Meropenem can be considered for use in patients with a self-reported nontype I penicillin allergy, and the incidence of allergic reactions is low and reactions are mild 7.
• Patients with a concomitant "sulfa" allergy or ≥3 other drug allergies were more likely to have an allergic reaction to meropenem or cephalosporins 7.