Toxic epidermal necrolysis (TEN) is a rare disease, which predominantly manifests as damage to the skin and mucosa. Antibiotics count among the most common triggers of this hypersensitive reaction. Patients with TEN are highly susceptible to infectious complications due to the loss of protective barriers and immunosuppressant therapy. The aim of this study was to investigate the potential relationship between antibiotics used before the development of TEN and early and late-onset infectious complications in TEN patients. In this European multicentric retrospective study (Central European Lyell syndrome: therapeutic evaluation (CELESTE)), records showed that 18 patients with TEN used antibiotics (mostly aminopenicillins) before the disease development (group 1), while in 21 patients, TEN was triggered by another factor (group 2). The incidence of late-onset infectious complications (5 or more days after the transfer to the hospital) caused by Gram-positive bacteria (especially by Enterococcus faecalis/faecium) was significantly higher in group 1 than in group 2 (82.4% vs. 35.0%, p = 0.007/pcorr = 0.014) while no statistically significant difference was observed between groups of patients with infection caused by Gram-negative bacteria, yeasts, and filamentous fungi (p > 0.05). Patients with post-antibiotic development of TEN are critically predisposed to late-onset infectious complications caused by Gram-positive bacteria, which may result from the dissemination of these bacteria from the primary focus.

4th Internal Haematology Department Charles University Faculty of Medicine and Teaching Hospital Sokolská 581 500 05 Hradec Králové Czech Republic

Central European Institute of Technology Brno University of Technology Purkyňova 656 123 612 00 Brno Czech Republic

Clinic of Maxillofacial Surgery Institution Shared with the University Hospital Brno Faculty of Medicine Masaryk University Jihlavska 20 625 00 Brno Czech Republic

Clinic of Stomatology Faculty of Medicine Masaryk University Pekarska 664 53 656 91 Brno Czech Republic

Department of Burns and Plastic Surgery Institution Shared with the University Hospital Brno Faculty of Medicine Masaryk University Kamenice 753 5 625 00 Brno Czech Republic

Department of Burns and Reconstructive Surgery 1st Private Hospital Košice Šaca Lucna 512 040 15 Košice Slovakia

Department of Burns and Reconstructive Surgery Faculty of Medicine Comenius University in Bratislava Ruzinovská 4 821 01 Bratislava Slovakia

Department of Clinical Microbiology University Hospital Brno Jihlavska 20 625 00 Brno Czech Republic

Department of Dermatovenerology Charles University Faculty of Medicine and Teaching Hospital Sokolská 581 500 05 Hradec Králové Czech Republic

Department of Military Surgery Faculty of Military Health Sciences University of Defence Třebešská 1575 500 01 Hradec Králové Czech Republic

Department of Molecular Pharmacy Faculty of Pharmacy Masaryk University Palackeho tr 1946 1 61200 Brno Czech Republic

Department of Paediatrics Charles University Faculty of Medicine and Teaching Hospital Sokolská 581 500 05 Hradec Králové Czech Republic

Department of Pathophysiology Faculty of Medicine Masaryk University Kamenice 753 5 625 00 Brno Czech Republic

Division of Plastic Surgery and Burns Treatment Department of Surgery Charles Univesrity Faculty of Medicine and Teaching Hospital Sokolská 581 500 05 Hradec Králové Czech Republic

Institute of Biostatistics and Analyses Faculty of Medicine Masaryk University Kamenice 753 5 625 00 Brno Czech Republic

Institute of Medical Genetics and Genomics Faculty of Medicine Masaryk University Kamenice 753 5 625 00 Brno Czech Republic

Prague Burn Center Charles University Faculty of Medicine and Teaching Hospital Kralovske Vinohrady Srobarova 1150 100 34 Prague Czech Republic

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$a Impact of Antibiotics Associated with the Development of Toxic Epidermal Necrolysis on Early and Late-Onset Infectious Complications / $c B. Lipovy, J. Holoubek, M. Hanslianova, M. Cvanova, L. Klein, I. Grossova, R. Zajicek, P. Bukovcan, J. Koller, M. Baran, P. Lengyel, L. Eimer, M. Jandova, M. Kostal, P. Brychta, P. Borilova Linhartova

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$a Toxic epidermal necrolysis (TEN) is a rare disease, which predominantly manifests as damage to the skin and mucosa. Antibiotics count among the most common triggers of this hypersensitive reaction. Patients with TEN are highly susceptible to infectious complications due to the loss of protective barriers and immunosuppressant therapy. The aim of this study was to investigate the potential relationship between antibiotics used before the development of TEN and early and late-onset infectious complications in TEN patients. In this European multicentric retrospective study (Central European Lyell syndrome: therapeutic evaluation (CELESTE)), records showed that 18 patients with TEN used antibiotics (mostly aminopenicillins) before the disease development (group 1), while in 21 patients, TEN was triggered by another factor (group 2). The incidence of late-onset infectious complications (5 or more days after the transfer to the hospital) caused by Gram-positive bacteria (especially by Enterococcus faecalis/faecium) was significantly higher in group 1 than in group 2 (82.4% vs. 35.0%, p = 0.007/pcorr = 0.014) while no statistically significant difference was observed between groups of patients with infection caused by Gram-negative bacteria, yeasts, and filamentous fungi (p > 0.05). Patients with post-antibiotic development of TEN are critically predisposed to late-onset infectious complications caused by Gram-positive bacteria, which may result from the dissemination of these bacteria from the primary focus.

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