BackgroundStreptococcus pneumoniaeis the most common bacterium that causes community-acquired pneumonia (CAP) in children. The rate ofS. pneumoniaeresistance to antibiotics is increasing, particularly in patients with severe CAP. Therefore, the level of antibiotic resistance ofS. pneumoniaecausing severe CAP in Vietnamese children requires regular monitoring.MethodsThis was a cross-sectional descriptive study. Nasopharyngeal aspiration specimens from children were cultured, isolated, and examined forS. pneumoniae. Bacterial strains were assessed for antimicrobial susceptibility, and the minimum inhibitory concentration (MIC) was determined.ResultsEighty-nine strains ofS. pneumoniaewere isolated from 239 children with severe CAP. The majority of isolates were completely non-susceptible to penicillin (1.1% intermediate, 98.9% resistant) and highly resistant to erythromycin (96.6%) and clarithromycin (88.8%); the rate of resistance to ceftriaxone was 16.9%, with the proportion of intermediate resistance at 46.0%; 100% of strains were susceptible to vancomycin and linezolid. For most antibiotics, MIC50and MIC90were equal to the resistance threshold according to the Clinical and Laboratory Standards Institute 2021; penicillin had an eight-fold increase in MIC90(64 mg/L) and ceftriaxone had a 1.5-fold increase in MIC90(6 mg/L).ConclusionStreptococcus pneumoniaeisolates described in this study were resistant to many antibiotics. Penicillin should not be the first-line antibiotic of choice, and ceftriaxone at an enhanced dose should be used instead.