{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T15:58:15Z","timestamp":1785513495694,"version":"3.56.0"},"reference-count":26,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Medicine and Pharmacy Carol Davila, Bucharest"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Drug provocation tests (DPTs) are the gold standard for evaluating delayed drug hypersensitivity reactions (DHRs), yet the lack of standardized protocols for non-mild reactions can lead to lifelong, unnecessary drug avoidance. Gradual DPTs (gDPTs) incorporating washout intervals offer an under-investigated strategy to minimize cumulative drug exposure. Our aim was to describe the safety and clinical outcomes of a gradual reintroduction strategy using washout intervals. Methods: We retrospectively analyzed patients evaluated at the University Hospital of Montpellier (primarily June 2018\u2013September 2023) with mainly moderate-to-severe delayed DHRs who underwent gDPTs across diverse drug classes. Washout intervals ranging from 24 h to 14 days were tailored to drug half-life, index DHR latency and severity. Results: Sixty-five patients (median age 54 years) reported 82 delayed DHRs; the 66 index reactions analyzed were predominantly triggered by beta-lactam antibiotics (83.3%), and danger signs were present in 74.2%. Seventy-seven tailored gDPTs were performed, mostly involving 3 or 4 steps and 7-day washout intervals (64.9%). Nine (11.7%, 95% CI: 5.5%\u201321.0%) were positive. gDPT events were elicited by culprit drugs, occurred within 48 h of the reactive dose, and were generally milder than index reactions; 88.9% occurred at \u226450% of the total planned dose. The workup enabled the delabeling of 68 previously discontinued drugs (52.7%). Conclusions: Our study provides a preliminary, hypothesis-generating proof-of-concept showing that washout intervals can limit cumulative exposure and identify early eliciting doses. Large-scale, standardized prospective studies are required to validate these findings and establish optimal protocols.<\/jats:p>","DOI":"10.3390\/ph19081201","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T15:02:01Z","timestamp":1785510121000},"page":"1201","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Drug Provocation Tests with Washout Intervals for Delayed Hypersensitivity Reactions: A Real-World Retrospective Analysis"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5188-6920","authenticated-orcid":false,"given":"Maria-Lucia","family":"Toader","sequence":"first","affiliation":[{"name":"Allergology Department, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Department of Allergology and Clinical Immunology, \u201cCarol Davila\u201d Nephrology Clinical Hospital, 010731 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1669-3975","authenticated-orcid":false,"given":"Selda","family":"Ali","sequence":"additional","affiliation":[{"name":"Allergology Department, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Department of Allergology and Clinical Immunology, \u201cCarol Davila\u201d Nephrology Clinical Hospital, 010731 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9339-1159","authenticated-orcid":false,"given":"Roxana Silvia","family":"Bumb\u0103cea","sequence":"additional","affiliation":[{"name":"Allergology Department, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Department of Allergology and Clinical Immunology, \u201cCarol Davila\u201d Nephrology Clinical Hospital, 010731 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Snejana","family":"Tintari","sequence":"additional","affiliation":[{"name":"Division of Allergy, Department of Pulmonology, Hospital Arnaud de Villeneuve, University Hospital of Montpellier, 34295 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca Mirela","family":"Chiriac","sequence":"additional","affiliation":[{"name":"Division of Allergy, Department of Pulmonology, Hospital Arnaud de Villeneuve, University Hospital of Montpellier, 34295 Montpellier, France"},{"name":"Department of Public Health, Institut Desbrest d\u2019Epid\u00e9miologie et de Sant\u00e9 Publique (IDESP), UMR UA11, INSERM, Montpellier University, 34093 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1001\/jama.2018.19283","article-title":"Evaluation and Management of Penicillin Allergy: A Review","volume":"321","author":"Shenoy","year":"2019","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1111\/j.1398-9995.2004.00678.x","article-title":"Diagnosis of Nonimmediate Reactions to \u0392-lactam Antibiotics","volume":"59","author":"Romano","year":"2004","journal-title":"Allergy"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1111\/all.13037","article-title":"Optimal Step Doses for Drug Provocation Tests to Prove Beta-Lactam Hypersensitivity","volume":"72","author":"Chiriac","year":"2017","journal-title":"Allergy"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1111\/all.15996","article-title":"EAACI\/ENDA Position Paper on Drug Provocation Testing","volume":"79","author":"Barbaud","year":"2024","journal-title":"Allergy"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1111\/cea.13380","article-title":"Can We Allow a Further Intake of Drugs Poorly Suspected as Responsible in Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)? 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