Does Imipenem (a Carbapenem antibiotic) exhibit cross-reactivity in patients with a Penicillin allergy?

From the Guidelines

Patients with a history of penicillin allergy can be administered imipenem without testing or additional precautions, according to the most recent guidelines. Imipenem, a carbapenem antibiotic, has a low cross-reactivity risk with penicillins, with an overall reported incidence of carbapenem allergy of 0.3%-3.7% 1. The beta-lactam ring structure shared between penicillins and carbapenems is the basis for potential cross-reactivity, but clinical evidence suggests this risk is low.

Key Points

• A systematic review of 838 patients with proven, suspected, or possible IgE-mediated penicillin allergy found that carbapenem reactions occurred in 4.3% of patients 1.
• Of the subset with positive skin tests to penicillin, only 1 (0.3%) had a reaction with symptoms consistent with a potentially IgE-mediated mechanism 1.
• A recent prospective study of 211 patients with skin test–confirmed penicillin allergy demonstrated that all tolerated carbapenems 1.

Clinical Considerations

• Patients with penicillin or cephalosporin allergy histories, as long as it is not a severe delayed cutaneous or organ-involved reaction, can receive carbapenems without prior testing 1.
• In certain patients or situations, such as multiple drug allergy or significant patient anxiety, a graded drug challenge might be preferred 1.
• The risk of cross-reactivity to any carbapenem is estimated to be 0.87% (95% CI: 0.32%-2.32%) 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. Before initiating therapy with Imipenem and Cilastatin for Injection (I.V.), careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, other beta-lactams and other allergens.

Imipenem may cross-react with penicillin allergy. Caution is advised when administering imipenem to patients with a history of penicillin hypersensitivity, as they may be at increased risk of experiencing severe hypersensitivity reactions.

• A careful inquiry should be made regarding previous hypersensitivity reactions to penicillins, cephalosporins, and other beta-lactams before initiating therapy with imipenem 2.

From the Research

Imipenem Cross-Reactivity with Penicillin Allergy

• Imipenem is a carbapenem antibiotic that has been shown to have cross-reactivity with penicillin in some studies 3, 4.
• A study published in 1988 found that half of the patients with a history of penicillin-allergic reactions also reacted to imipenem reagents, suggesting a good correlation between the penicillin and imipenem reagents to which the patients reacted 3.
• However, a retrospective study published in 2004 found that the incidence of cross-hypersensitivity reactions between penicillin and carbapenems, including imipenem, may be lower than previously reported, with only 9.2% of patients with a reported penicillin allergy developing a hypersensitivity reaction to meropenem or imipenem/cilastatin 4.
• More recent studies have suggested that the rate of cross-reactivity between penicillin and carbapenems is likely lower than 1% 5, and that carbapenem use may be reasonable for penicillin-allergic patients if caution is exercised 4, 5.

Evaluation and Management of Penicillin Allergy

• The evaluation and management of penicillin allergy is an important tool for antimicrobial stewardship, as many patients report allergies to penicillin that may not be clinically significant 6, 7.
• Penicillin skin testing and amoxicillin challenge can be used to evaluate patients with a history of penicillin allergy, and can help to identify patients who are at low risk of reacting to penicillin 6, 7.
• Patients with a low-risk history of penicillin allergy can be considered for direct amoxicillin challenge, while those with a moderate-risk history can be evaluated with penicillin skin testing 6.
• The use of carbapenems, including imipenem, should be considered on a case-by-case basis in patients with a history of penicillin allergy, taking into account the potential risks and benefits of treatment 4, 5.