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Abstract Background Understanding the epidemiology of Streptococcus pneumoniae (S. pneumoniae) isolates is important for pneumonia treatment and prevention. This research aimed to explore the epidemiological characteristics of S. pneumoniae isolated from pediatric inpatients and outpatients during the same period. Methods S. pneumoniae were isolated from unsterile samples of inpatients and outpatients younger than five years old between March 2013 and February 2014. The serotypes were determined using diagnostic pneumococcal antisera. The resistance of each strain to 13 antibiotics was tested using either the E-test or the disc diffusion method. The Sequence Types (STs) were analyzed via Multilocus Sequence Typing (MLST). Results The dominant serotypes obtained from inpatients were 19F (32.9 %), 19A (20.7 %), 23F (10.7 %), 6A (10.0 %), and 14 (8.6 %), while those from outpatients were 19F (13.6 %), 23F (12.9 %), 6A (10.0 %), 6B (10.0 %), and 19A (7.9 %). The coverage rates of 13-valent Pneumococcal Conjugate Vaccine (PCV) formulations were high in both groups. The nonsusceptibility to penicillin, cefuroxime, imipenem, erythromycin, and trimethoprim-sulfamethoxazole among the inpatient isolates was 7.1 %, 92.8 %, 65.7 %, 100 %, and 85.0 %, respectively, while that among the outpatient isolates was 0.7 %, 50.0 %, 38.6 %, 96.4 %, and 65.7 %, respectively. There were 45 and 81 STs detected from the pneumococci isolated from inpatients and outpatients, respectively. CC271 was common among both inpatients and outpatients (43.6 % and 14.3 %). Conclusions Pneumococcal vaccine-related serotypes are prevalent among both inpatients and outpatients, especially among inpatients, who exhibit more severe antibiotic resistance. Therefore, universal immunization with PCV13 would decrease the hospitalization rate due to S. pneumoniae and the antibiotic resistance rate of S. pneumoniae. S (S prevention period 201 2014 antisera 1 Etest E test method (STs MLST. MLST . (MLST) F 32.9 329 32 9 (32. , %) A 20.7 207 20 7 (20. 10.7 107 10 (10. 10.0 0 8.6 86 8 6 (8. 13.6 136 (13. 12.9 129 12 (12. B 7.9 79 (7. %. 13valent valent PCV (PCV groups penicillin cefuroxime imipenem erythromycin trimethoprimsulfamethoxazole trimethoprim sulfamethoxazole 71 7. 928 92 92. 657 65 65. 850 85 85. respectively 07 0. 500 50 50. 386 38 38. 964 96 4 96. CC CC27 43.6 436 43 (43. 143 3 14. vaccinerelated vaccine related Therefore PCV1 (MLST 32. (32 20. 2 (20 10. (10 8. (8 13. (13 12. (12 (7 5 CC2 43. (43 (3 (2 (1 ( (4