Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and severe immune-mediated adverse reactions affecting the skin and mucous membranes, representing the most critical types of drug eruptions. SJS and TEN represent different severities of the same disease entity, with TEN being the more severe form. Classification is based on the percentage of involved body surface area (BSA), where BSA < 10% indicates SJS, BSA > 30% indicates TEN, and BSA between 10% and 30% is classified as SJS/TEN overlap syndrome. The global annual incidence of SJS/TEN is up to 12 cases per million people [1]. Symptoms often begin with flu-like signs, and the disease predominantly affects the skin, oral cavity, eyes, and urogenital areas, resulting in skin blisters, large bullae, epidermal detachment, mucosal erosions, etc. Severe cases may present with systemic toxic symptoms and varying degrees of internal organ involvement. Due to extensive skin detachment, acute complications include massive fluid loss, infections, sepsis, gastrointestinal bleeding, electrolyte imbalance, and multi-organ failure syndrome, posing a high risk of mortality. Studies have shown mortality rates is 13% for SJS, 43% for SJS/TEN overlap forms, and 49% for TEN [2]. Additionally, the mortality rate for patients with SJS/TEN was reported to be 23% at 6 weeks and 34% at 1 y, measured from the onset of the reaction [3].

The pathogenesis of SJS/TEN remains incompletely understood, primarily attributed to drug-specific cytotoxic reactions causing keratinocytes apoptosis and necrosis directly and indirectly. The drugs most commonly implicated in SJS/TEN include antibiotics, antiepileptic drugs, antineoplastic agents, and nonsteroidal anti-inflammatory drugs, with over half of SJS/TEN cases attributed to antibiotics [4]. In recent years, several individual drugs, such as penicillins, cephalosporins, macrolides, tetracyclines, quinolones, and sulphonamides, have been reported to carry both relative and absolute risks of SJS/TEN [[5], [6], [7]]. A recent Japanese case-crossover study [8] revealed associations between SJS/TEN and lincomycin, glycopeptides, aminoglycosides, phosphomycin, and carbapenems. However, due to limitations in case numbers, further validation is required, particularly for the risk associations of glycopeptides, carbapenems, and lincomycin with SJS/TEN, necessitating ongoing monitoring in the future. Reports of antibiotic-induced SJS/TEN have recently become more frequent, involving nearly all types of antibiotics. Nevertheless, further research with larger sample sizes is needed to elucidate the risk associations between these antibiotics and SJS/TEN.

Currently, there is a lack of comprehensive comparative analyses regarding the association between different antibiotics and the risk of SJS/TEN. Additionally, both infection and antibiotics are risk factors for triggering SJS/TEN, but the risk differences associated with the use of different antibiotics for various infections remain unclear. Hence, this study aims to explore signals of antibiotics associated with SJS/TEN using data from the FDA Adverse Event Reporting System (FAERS) database, uncovering potential drug-induced risk signals that may increase the risk of SJS/TEN in infected patients. The research will evaluate the risk levels of SJS/TEN associated with specific antibiotics and infectious diseases, providing evidence to guide clinical drug selection and reduce the occurrence of SJS/TEN events. Ultimately, this study may offer valuable information on antibiotic safety and enhance medication safety for infected patients.