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Background: Cross-reactivity between aztreonam and β-lactams is poor, but tolerability of aztreonam has been assessed in a few groups of patients suffering from IgE-mediated allergy to β-lactams. The aim of this study was to assess the cross-reactivity of aztreonam with other β-lactams and its tolerability in patients with cell-mediated allergy to these drugs. Methods: We studied 78 patients with cell-mediated allergy to β-lactams who underwent skin prick, immediate and delayed-reading intradermal tests as well as patch tests with penicilloyl-polylysine, minor determinant mixture, semi-synthetic penicillins, cephalosporins, aztreonam and imipenem. Patients with negative allergy testing with aztreonam underwent an intramuscular test dosing and were observed for 3 h. Results: Our patients experienced 94 non-immediate reactions; delayed-onset urticaria (34 cases), maculopapular exanthema (13 cases), urticaria/angioedema (15 cases) and itching erythema (13 cases) were the most reported symptoms. Amoxicillin (35 cases), ampicillin (28 cases) and bacampicillin (18 cases) were the most involved drugs. All patients had a positive patch test and/or a positive delayed-reading intradermal test to at least 1 β-lactam antibiotic and none had a positive patch or delayed-reading intradermal test to aztreonam. Then, 65 patients underwent intramuscular test dosing with aztroenam, and none of them had a clinical reaction. Conclusions: Our data confirm the lack of cross-reactivity between β-lactams and aztreonam in patients with cell-mediated allergy to these drugs. Delayed-reading intradermal tests and patch tests with aztreonam represent a simple and rapid diagnostic tool to establish tolerability in β-lactam-allergic patients. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]