{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:12:43Z","timestamp":1788415963082,"version":"build-2803163510"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cutaneous adverse drug reactions (CADRs) are triggered by numerous antibiotic drugs. Most drug reactions are in the spectrum of a maculopapular eruption (MPE) with a self-limiting disease course. In contrast, severe cutaneous adverse reactions (SCARs), including Stevens\u2013Johnson syndrome\/toxic epidermal necrolysis (SJS\/TEN), are rare but may follow a life-threatening course. In this study, we investigated the key drug-related triggers of CADRs in a retrospective single-center cohort and, based on these findings, evaluated the differential risk of the implicated agents using large-scale real-world data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Data from 122 patients diagnosed with CADRs, including 5 with confirmed SJS\/TEN treated at a tertiary-referral hospital were retrospectively analyzed in a descriptivesingle-center cohort study. To further explore our findings, we performed a large-scale real-world cohort study using TriNetX to assess the occurrence of SJS\/TEN following exposure to selected drugs. Separate analyses were conducted comparing ceftriaxone with aminopenicillins, cefazolin, cefuroxime, and allopurinol, which was included as a positive control. Odds ratios were calculated after running propensity-score-matching for demographic characteristics and SJS\/TEN-risk factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the single-center cohort, MPE was the predominant phenotype among CADRs attributed to aminopenicillins and first- and second-generation cephalosporins. In contrast, among CADRs attributed to third-generation cephalosporins, represented by ceftriaxone in this single-center cohort, SCARs were the predominant reaction type, with ceftriaxone accounting for 40% of SJS\/TEN cases. These findings were underlined by the real-world cohort analysis, in which aminopenicillins and early-generation cephalosporins showed significantly lower odds of SJS\/TEN than ceftriaxone (0.389 (95% CI 0.291\u20130.520) for aminopenicillins; 0.392 (0.290\u20130.529) for cefazolin; 0.300 (0.157\u20130.572) for cefuroxime).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>While both datasets need to be interpreted within the context of their respective limitations, our analysis, are in line with previous studies, suggesting that ceftriaxone may have an SJS\/TEN risk profile that exceeds the class-wide risk observed among cephalosporins. This underscores the importance of substance-specific, rather than purely class-based approaches in both clinical research and pharmacovigilance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1875934","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:15:30Z","timestamp":1788412530000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Differential risk signals of cutaneous adverse drug reactions among \u03b2-lactam antibiotics: ceftriaxone shows increased signals for SJS\/TEN in clinical and real-world cohorts"],"prefix":"10.3389","volume":"13","author":[{"given":"Leonard","family":"von Grundherr","sequence":"first","affiliation":[{"name":"L\u00fcbeck Institute of Experimental Dermatology, University of L\u00fcbeck","place":["L\u00fcbeck, Germany"]},{"name":"Department of Dermatology, University of L\u00fcbeck","place":["L\u00fcbeck, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrike Alexandra","family":"Faesser","sequence":"additional","affiliation":[{"name":"Department of Medicine III, Pulmonology, University-Hospital Schleswig-Holstein","place":["L\u00fcbeck, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Recke","sequence":"additional","affiliation":[{"name":"L\u00fcbeck Institute of Experimental Dermatology, University of L\u00fcbeck","place":["L\u00fcbeck, Germany"]},{"name":"Department of Dermatology, University of L\u00fcbeck","place":["L\u00fcbeck, Germany"]},{"name":"Comprehensive Center for Inflammation Medicine, University-Hospital Schleswig-Holstein","place":["L\u00fcbeck, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf J.","family":"Ludwig","sequence":"additional","affiliation":[{"name":"L\u00fcbeck Institute of Experimental Dermatology, University of L\u00fcbeck","place":["L\u00fcbeck, Germany"]},{"name":"Comprehensive Center for Inflammation Medicine, University-Hospital Schleswig-Holstein","place":["L\u00fcbeck, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Boch","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of L\u00fcbeck","place":["L\u00fcbeck, Germany"]},{"name":"Department of Dermatology and Allergology, UniversityHospital Munich, LMU","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Curman","sequence":"additional","affiliation":[{"name":"L\u00fcbeck Institute of Experimental Dermatology, University of L\u00fcbeck","place":["L\u00fcbeck, Germany"]},{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet","place":["Stockholm, Sweden"]},{"name":"Department of Medicine (Solna), Division of Dermatology and Venereology, Karolinska Institutet","place":["Stockholm, Sweden"]},{"name":"Dermato-Venereology Clinic, Karolinska University Hospital","place":["Stockholm, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1957","DOI":"10.1111\/jdv.16339","article-title":"Clinical and pathogenic aspects of the severe cutaneous adverse reaction epidermal necrolysis (EN)","volume":"34","author":"Kuijper","year":"2020","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2492","DOI":"10.1056\/NEJMcp1104080","article-title":"Clinical practice. Exanthematous drug eruptions","volume":"366","author":"Stern","year":"2012","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1046\/j.1523-1747.2000.00061.x","article-title":"SCORTEN: a severity-of-illness score for toxic epidermal necrolysis","volume":"115","author":"Bastuji-Garin","year":"2000","journal-title":"J Invest Dermatol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1016\/j.iac.2022.10.005","article-title":"Drug hypersensitivity reactions","volume":"43","author":"Wilkerson","year":"2023","journal-title":"Immunol Allergy Clin North Am"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1838","DOI":"10.1111\/bcp.15490","article-title":"Drugs and the skin: a concise review of cutaneous adverse drug reactions","volume":"90","author":"Del Pozzo-Maga\u00f1a","year":"2024","journal-title":"Br J Clin Pharmacol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"96","DOI":"10.5414\/ALX01508E","article-title":"Epidemiology of cutaneous adverse drug reactions","volume":"1","author":"Mockenhaupt","year":"2017","journal-title":"Allergol Select"},{"key":"B7","doi-asserted-by":"publisher","first-page":"627","DOI":"10.3238\/arztebl.2016.0627","article-title":"Polypharmacy-an upward trend with unpredictable effects","volume":"113","author":"Mo\u00dfhammer","year":"2016","journal-title":"Dtsch Arztebl Int"},{"key":"B8","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1007\/s40629-025-00350-y","article-title":"Cutaneous drug reactions: classification, diagnosis, clinical and therapeutic consequences","volume":"34","author":"Paster","year":"2025","journal-title":"Allergo J Int"},{"key":"B9","doi-asserted-by":"publisher","first-page":"38","DOI":"10.25646\/5873","article-title":"Developments in life expectancy in Germany. Current trends","volume":"4","author":"Nowossadeck","year":"2019","journal-title":"J Health Monit"},{"key":"B10","doi-asserted-by":"publisher","first-page":"111","DOI":"10.3390\/dermatopathology9020014","article-title":"Histopathologic features of maculopapular drug eruption","volume":"9","author":"Ernst","year":"2022","journal-title":"Dermatopathology"},{"key":"B11","doi-asserted-by":"publisher","first-page":"122","DOI":"10.5414\/ALX02422E","article-title":"Guideline for allergological diagnosis of drug hypersensitivity reactions","volume":"7","author":"Brockow","year":"2023","journal-title":"Allergol Select"},{"key":"B12","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1007\/s40257-024-00889-6","article-title":"Update on Stevens\u2013Johnson syndrome and toxic epidermal necrolysis: diagnosis and management","volume":"25","author":"Shah","year":"2024","journal-title":"Am J Clin Dermatol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"100673","DOI":"10.1016\/j.waojou.2022.100673","article-title":"DRESS Syndrome: a literature review and treatment algorithm","volume":"16","author":"Calle","year":"2023","journal-title":"World Allergy Organ J"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1016\/j.jaci.2022.08.028","article-title":"Drug allergy: a 2022 practice parameter update","volume":"150","author":"Khan","year":"2022","journal-title":"J Allergy Clin Immunol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1117391","DOI":"10.3389\/fphar.2023.1117391","article-title":"Severe cutaneous adverse reactions to drugs: a real-world pharmacovigilance study using the FDA adverse event reporting system database","volume":"14","author":"Li","year":"2023","journal-title":"Front Pharmacol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/j.anai.2019.08.004","article-title":"Drug-induced severe cutaneous adverse reactions: determine the cause and prevention","volume":"123","author":"Zhang","year":"2019","journal-title":"Ann Allergy Asthma Immunol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.ejim.2015.11.017","article-title":"Adverse drug reactions and organ damage: the skin","volume":"28","author":"Marzano","year":"2016","journal-title":"Eur J Intern Med"},{"key":"B18","doi-asserted-by":"publisher","first-page":"36","DOI":"10.23750\/abm.v90i3-S.8159","article-title":"Mild cutaneous reactions to drugs","volume":"90","author":"Crisafulli","year":"2019","journal-title":"Acta Biomed"},{"key":"B19","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.jdrv.2025.07.007","article-title":"A systematic review of symmetrical drug-related intertriginous and flexural exanthema","volume":"6","author":"Koh","year":"2025","journal-title":"JAAD Reviews"},{"key":"B20","doi-asserted-by":"publisher","first-page":"102909","DOI":"10.1016\/j.eclinm.2024.102909","article-title":"Erythema multiforme","volume":"77","author":"Kechichian","year":"2024","journal-title":"eClinicalMed"},{"key":"B21","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1007\/s00105-017-4117-y","article-title":"Lichenoid drug reactions","volume":"69","author":"Merk","year":"2018","journal-title":"Hautarzt"},{"key":"B22","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1684\/ejd.2011.1550","article-title":"Identifying prognostic factors for drug rash with eosinophilia and systemic symptoms (DRESS)","volume":"21","author":"Wei","year":"2011","journal-title":"Eur J Dermatol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1111\/j.1468-3083.2008.02585.x","article-title":"Clinicopathological features and prognosis of drug rash with eosinophilia and systemic symptoms: a study of 30 cases in Taiwan","volume":"22","author":"Chiou","year":"2008","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1001\/archderm.136.3.323","article-title":"Toxic epidermal necrolysis and Stevens-Johnson syndrome: does early withdrawal of causative drugs decrease the risk of death?","volume":"136","author":"Garcia-Doval","year":"2000","journal-title":"Arch Dermatol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1038\/sj.jid.5701033","article-title":"Stevens-Johnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study","volume":"128","author":"Mockenhaupt","year":"2008","journal-title":"J Invest Dermatol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1111\/bjd.12501","article-title":"Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Results from the prospective RegiSCAR study","volume":"169","author":"Kardaun","year":"2013","journal-title":"Br J Dermatol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.1016\/j.jid.2017.12.015","article-title":"Antibiotic drug use and the risk of Stevens-Johnson syndrome and toxic epidermal necrolysis: a population-based case-control study","volume":"138","author":"Frey","year":"2018","journal-title":"J Invest Dermatol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1001\/jamadermatol.2022.6378","article-title":"Worldwide prevalence of antibiotic-associated Stevens-Johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis","volume":"159","author":"Lee","year":"2023","journal-title":"JAMA Dermatol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1001\/archderm.1993.01680220104023","article-title":"Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme","volume":"129","author":"Bastuji-Garin","year":"1993","journal-title":"Arch Dermatol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1001\/archderm.138.8.1019","article-title":"Correlations between clinical patterns and causes of erythema multiforme majus, Stevens-Johnson syndrome, and toxic epidermal necrolysis: results of an international prospective study","volume":"138","author":"Auquier-Dunant","year":"2002","journal-title":"Arch Dermatol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1034\/j.1600-0560.2001.028003113.x","article-title":"Acute generalized exanthematous pustulosis (AGEP)\u2013a clinical reaction pattern","volume":"28","author":"Sidoroff","year":"2001","journal-title":"J Cutan Pathol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1516126","DOI":"10.3389\/fphar.2025.1516126","article-title":"A comprehensive review of methodologies and application to use the real-world data and analytics platform TriNetX","volume":"16","author":"Ludwig","year":"2025","journal-title":"Front Pharmacol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.alit.2021.01.004","article-title":"Risk of Stevens-Johnson syndrome and toxic epidermal necrolysis associated with anticonvulsants in a Japanese population: matched case\u2013control and cohort studies","volume":"70","author":"Fukasawa","year":"2021","journal-title":"Allergol Int"},{"key":"B34","doi-asserted-by":"publisher","first-page":"12575","DOI":"10.2147\/JIR.S546186","article-title":"Viral triggers exposed: a systematic review of virus-induced Stevens-Johnson syndrome\/toxic epidermal necrolysis","volume":"18","author":"Fetriani","year":"2025","journal-title":"J Inflamm Res"},{"key":"B35","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1016\/j.burns.2019.10.008","article-title":"Retrospective study of 213 cases of Stevens-Johnson syndrome and toxic epidermal necrolysis from China","volume":"46","author":"Yang","year":"2020","journal-title":"Burns"},{"key":"B36","doi-asserted-by":"publisher","first-page":"675","DOI":"10.3390\/ph17060675","article-title":"Stevens-Johnson syndrome and toxic epidermal necrolysis: analysis of the Russian database of spontaneous reports","volume":"17","author":"Zyryanov","year":"2024","journal-title":"Pharmaceuticals (Basel)"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1875934\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:15:33Z","timestamp":1788412533000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1875934\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":36,"alternative-id":["10.3389\/fmed.2026.1875934"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1875934","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]},"article-number":"1875934"}}