What is the cross-reactivity between penicillin and carbapenems (Carbapenem antibiotics) in patients with a penicillin allergy?

From the Guidelines

Cross-reactivity between penicillin and carbapenems in patients with penicillin allergy is low, and carbapenems can be administered without testing or additional precautions, according to a 2022 practice parameter update 1. This means that most patients with penicillin allergy can safely receive carbapenem antibiotics. The estimated cross-reactivity is about 0.3%-4.3% in patients with proven, suspected, or possible IgE-mediated penicillin allergy 1. Key points to consider include:

• The overall reported incidence of carbapenem allergy is 0.3%-beta-lactams cross-reactivity is also low 1
• A systematic review covering 10 studies and 12 case reports included 838 patients with proven, suspected, or possible IgE-mediated penicillin allergy, and carbapenem reactions occurred in 4.3% of patients (95% CI: 3.1%-5.9%) 1
• Another systematic review and meta-analysis covering 11 observational studies including 1127 patients demonstrated a risk of cross-reactivity to any carbapenem as 0.87% (95% CI: 0.32%-2.32%) 1 However, caution is still warranted in patients with severe, immediate-type (IgE-mediated) penicillin allergies, such as anaphylaxis, angioedema, or urticaria. For these patients, skin testing before carbapenem administration may be considered, or administration under careful monitoring if the carbapenem is deemed necessary 1. When administering carbapenems to patients with penicillin allergy, healthcare providers should still be prepared to manage potential allergic reactions, even though they are uncommon. The first dose should ideally be given in a monitored setting with emergency medications readily available, especially for patients with severe penicillin allergy history. In certain patients or situations, such as multiple drug allergy or significant patient anxiety, a graded drug challenge might be preferred 1.

From the FDA Drug Label

There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe hypersensitivity reactions when treated with another beta-lactam.

The cross-reactivity between penicillin and carbapenems in patients with a penicillin allergy is a concern, as severe hypersensitivity reactions have been reported in individuals with a history of penicillin hypersensitivity who were treated with another beta-lactam, such as carbapenems 2.

• Key points to consider:
  • A history of penicillin hypersensitivity may increase the risk of a hypersensitivity reaction to carbapenems.
  • Careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, other beta-lactams, and other allergens before initiating therapy with carbapenems.
  • If an allergic reaction to carbapenems occurs, the drug should be discontinued immediately, and emergency treatment should be provided as clinically indicated.

From the Research

Cross-Reactivity Between Penicillin and Carbapenems

• The cross-reactivity between penicillin and carbapenems in patients with a penicillin allergy is a significant concern in clinical practice 3, 4, 5, 6, 7.
• Studies have shown that the true incidence of cross-hypersensitivity reactions between penicillin and carbapenems may be lower than previously reported, with some studies suggesting a cross-reactivity rate of less than 1% 3, 5.
• A retrospective study found that 9.2% of patients with a reported penicillin allergy developed a hypersensitivity reaction to meropenem or imipenem/cilastatin, while 3.9% of patients without penicillin allergy developed a hypersensitivity reaction to these carbapenems 3.
• Another study found that 110 patients with non-anaphylactic and anaphylactic penicillin allergic reactions tolerated prolonged meropenem therapy safely without any allergic reactions 4.

Risk Factors and Tolerability

• The risk of cross-sensitivity between penicillins and carbapenems is less than 1% in patients with a positive penicillin skin test 5.
• Data on cross-sensitivity between cephalosporins and carbapenems are limited, but the risk appears to be low 5, 6.
• Studies have shown that aztreonam and carbapenems can be tolerated in patients with IgE-mediated hypersensitivity to penicillins, with cross-reactivity rates ranging from 1% to 6.2% 6, 7.
• Pretreatment skin tests are recommended for patients who require alternative β-lactams, as negative results indicate tolerability 6, 7.

Clinical Implications

• Carbapenem use may be reasonable for penicillin-allergic patients if caution is exercised 3.
• Meropenem may be safely given to patients with known or unknown allergic reactions to penicillins, including those with anaphylactic reactions, without penicillin skin testing 4.
• The tolerability of aztreonam and carbapenems in penicillin-allergic subjects suggests that these alternative β-lactams can be used in patients who require them 7.