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Suspected or confirmed antibiotic allergy is a frequent clinical circumstance that influences antimicrobial prescription and often leads to the avoidable use of less efficacious and/or more toxic or costly drugs than first-line antimicrobials. Optimizing antimicrobial therapy in patients with antibiotic allergy labels has become one of the priorities of antimicrobial stewardship programs in several countries. These guidelines aim to make recommendations for the systematic approach to patients with suspected or confirmed antibiotic allergy based on current evidence. An expert panel (11 members of various scientific societies) formulated questions about the management of patients with suspected or confirmed antibiotic allergy. A systematic literature review was performed by a medical librarian. The questions were distributed among panel members who selected the most relevant references, summarized the evidence, and formulated graded recommendations when possible. The answers to all the questions were finally reviewed by all panel members. A systematic approach to patients with suspected or confirmed antibiotic allergy was recommended to improve antibiotic selection and, consequently, clinical outcomes. A clinically oriented, 3-category risk-stratification strategy was recommended for patients with suspected antibiotic allergy. Complementary assessments should consider both clinical risk category and preferred antibiotic agent. Empirical therapy recommendations for the most relevant clinical syndromes in patients with suspected or confirmed ß-lactam allergy were formulated, as were recommendations on the implementation and monitoring of the impact of the guidelines. Antimicrobial stewardship programs and allergists should design and implement activities that facilitate the most appropriate use of antibiotics in these patients.