Abstract: OBJECTIVE To explore the drug resistance and clinical characteristics of various age groups of children with Mycoplasma pneumoniae pneumonia (MPP). METHODS The clinical data of 475 children with MPP who were treated in Taikang Tongji (Wuhan) Hospital from Aug. 2023 to Dec. 2023 were retrospectively analyzed. The children were divided into the drug-resistant group with 411 cases and the non-drug-resistant group with 64 cases. The gender, age, clinical manifestations, imaging manifestations, extrapulmonary complications,severity of MPP, inflammatory reaction-related indicators white blood cell (WBC), neutrophil percentage (N%), C-reactive protein (CRP), serum amyloid A (SAA), procalcitonin (PCT), use of anti-MPP drugs and length of hospital stay were observed and compared between the two groups. The above indicators were also compared among the age groups. RESULTS The detection rate of drug resistance genes was 86.53% (411/475). The proportion of the children with lung consolidation, atelectasis, pleural effusion, extrapulmonary complications, severe MPP, oral clarithromycin, and intravenous drip of azithromycin were higher in the drug-resistant group than in the non-drug-resistant group; the proportion of the children who were treated with oral administration of azithromycin was lower in the drug-resistant group than in the non-drug-resistant group; the fever duration and length of hospital stay were longer in the drug-resistant group than in the non-drug-resistant group; there were significant differences (P＜0.05). There were significant differences in fever duration, proportion of children with dyspnea, WBC, N%, SAA, proportion of children with oral administration of azithromycin, proportion of children with oral administration of clarithromycin, and proportion of children with intravenous drip of azithromycin among the age groups (P＜0.05). CONCLUSIONS tNGS can effectively detect the drug resistance genes. The positive test of drug resistance genes may be associated with the complications, severity of disease, length of hospital stay and medication regimen. Additionally, the age of the children with MPP may be associated with the inflammation, fever duration and medication regimen.