(BSPOT27) Severe Cutaneous Adverse Reactions Associated with Antibiotics in Pediatric Patients

Background: Severe cutaneous adverse reactions (SCARs) are life-threatening adverse effects caused by drugs, but predicting them is challenging due to their complexity. While the epidemiology of SCARs and antibiotics in adults is well-documented, research in pediatric populations is limited.

Objectives: To investigate the association between SCARs and antibiotics in pediatric patients

Methods: This study utilized the Health Insurance Review and Assessment Service–Pediatric Patient Sample (HIRA-PPS) claims database spanning from 2009 to 2019, which includes annual 10% stratified randomized samples of pediatric patients under 20 years old. SCARs were defined as patients admitted with drug rash with eosinophilia and systemic symptoms (DRESS: ICD 10 code L27), Stevens-Johnson Syndrome (SJS: ICD 10 code L511), and Toxic Epidermal Necrolysis (TEN: ICD 10 code L512). Self-controlled case crossover (CCO) study was conducted, defining SCARs incidence as the absence of a diagnosis for at least 6 months. Antibiotics were investigated, and other drugs such as antiepileptics, non-steroidal anti-inflammatory drugs (NSAIDS), acetaminophen, tramadol, and anti-tuberculosis agents were also examined as potential causative agents. The adjusted odds ratios (aORs) with 95% confidence intervals (CI) were calculated to assess the risk of SCARs associated with antibiotic use during the hazard period (1-30 days before the index date) compared to the control period 1 (61-90 days before the index date), using the conditional logistic regression. We also performed sensitivity analyses using three alternative control periods (91-120, 121-150, 151-180 days before the index date).

Results: From 2009 to 2019, a total of 749 cases of SCARs were identified among 11,471,090 pediatric patients, yielding an annual prevalence rate of 6.5 per 100,000 individuals. Among these cases, DRESS, TEN, and SJS accounted for 650 (86.8%), 100 (13.4%), and 13 (1.7%) cases, respectively. Regarding age distribution, 417patients (55.7%) were aged 0-9 years, while 332patients (44.3%) were aged 10-19 years. In CCO, the prescription of antibiotics during hazard period was associated with about 2.9-fold higher risk of SCARs compared to the control period 1 (aOR=2.9, 95%CI=1.8-4.8). This tendency remained consistent in sensitivity analysis using different control periods. Regarding the individual classes of antibiotics, the use of cephalosporins and multiple antibiotics was significantly associated with the occurrence of SCARs across various control periods.

Conclusions: These findings underscore the importance of exercising caution when prescribing antibiotics to pediatric patients to mitigate the risk of SCARs.