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Introduction: Streptococcus pneumoniae is the most common cause of community-acquired pneumonia (CAP) in children. Recently, the rapid emergence of antibiotic-resistant pneumococci has posed enormous challenges for CAP treatment and public health. This study aims to provide clinicians with updated data about the antimicrobial susceptibility of S. pneumoniae and improve the treatment guidelines in CAP in children. Methods: This cross-sectional and in-vitro study was conducted at three hospitals in Quang Nam province and Da Nang city in Vietnam. Pneumococcal strains were isolated from nasopharyngeal aspirate samples of 360 CAP in-patients under five years of age. The susceptibility of clinically used antibiotics was investigated using the disk diffusion test and the E-test for identifying the MIC. Multi-drug resistant (MDR) S. pneumoniae isolates were also determined. Results: 21.9% of CAP children patients were pneumococcal carriage. The susceptibility testing demonstrated that all 56 tested pneumococcal isolates were resistant to erythromycin and azithromycin, whereas none of the isolates developed the resistance to levofloxacin, vancomycin, and linezolid. The clindamycin- and cotrimoxazole-resistant pneumococci rates were 96.4% and 87.5%, respectively. For β-lactam antibiotics, the resistance proportions of pneumococcal isolates to penicillin G, co-amoxiclav, amoxicillin, cefotaxime, and ceftriaxone were 3.6%,1.8%, 1.8%, 1.8%, and 3.6%, respectively. 83.9% of the tested isolates were MDR S. pneumoniae. Conclusion: Our data support using penicillin G, amoxicillin, co-amoxiclav, or cefotaxime as the first-line therapy for uncomplicated-pneumococci-induced CAP in Quang Nam – Da Nang, while vancomycin, linezolid, and levofloxacin should be used as alternatives or in MDR cases.