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Background: Staphylococcal Scalded Skin Syndrome (SSSS) is caused by a special type of Staphylococcus aureus (S.aureus) which can produce exfoliative toxins. The generalized SSSS is recommended to be admitted and treated with intravenous antibiotics. However, there were limited reports on whether personal and clinical factors can have impacts on the duration of intravenous antibiotic application for pediatric patients with generalized SSSS.We performed a study to assess the factors affecting intravenous antibiotic treatment course of SSSS patients. Additionally, the positive culture rates of S.aureus in different samples and the antibiotic-resistant profile were investigated. Methods: 219 patients with generalized SSSS were included. Gender, age, area, season, maximum axillary temperature, white blood cell(WBC) count, C-reactive protein (CRP) level, types of intravenous antibiotics, and types of external antibiotics were recorded as the baseline. Simple linear regression was applied in the univariate analysis to determine the variables with statistical significance and then these variables were further examined in multivariate linear regression model. The positive culture rates of S.aureus in different samples and the drug sensitivity results were statistically compared by Fisher’s exact test and pairwise Chi square test respectively. Results: According to the multiple linear regression, older ages (β=-0.01, p <0.05) and external application of fusidic acid (β=-1.57, p <0.05) were associated with shorter treatment course, elevated leukocytes (β=0.11, p <0.001) and CRP level (β=1.64, p <0.01) were associated with longer treatment course. The positive culture rates of periorificial (54.55%) and throat swabs (30.77%) were higher than the ones of blood samples (5.97%) (p <0.01). The resistant rates of levofloxacin (8.33%), gentamycin (8.33%), tetracycline (25%), oxacillin (8.33%), vancomycin (0%) were significantly lower than the ones of erythromycin (100%), trimethoprim-sulfamethoxazole (TMP/SMX) (83.33%), clindamycin (91.67%), penicillin G(100%) (p <0.001).Conclusion: Elevated leukocytes and CRP level indicated prolonged intravenous antibiotic treatment course. Older ages and external application of fusidic acid helped to reduce the treatment course. Periorificial and throat swabs were useful to identify causative S.aureus. Oxacillin and vancomycin resistance was rare and clindamycin resistance was common. Clindamycin monotherapy for SSSS should be avoided.