BACKGROUND: Neonatal purulent meningitis is a purulent bacterial infection associated with high morbidity and mortality. Conventional antibiotics are becoming less effective due to increasing drug resistance. Moreover, there are variations in the disease-causing bacterial species according to regions, with the pathogens undergoing continuous evolution. Therefore, this study aimed to compare and analyze dynamic changes of pathogenic distribution and drug resistance mechanisms in neonatal suppurative meningitis, emphasize the importance of continuous microbiological surveillance and epidemiological monitoring to guide antimicrobial stewardship and optimize antibiotic treatment strategies, ultimately reducing neonatal morbidity and mortality. METHODS: We retrospectively analyzed newborns diagnosed with suppurative meningitis having positive cerebrospinal fluid cultures between January 2017 and December 2022. Pathogenic distribution and drug resistance mechanisms were analyzed among the years and compared between preterm and full-term neonates. RESULTS: Among the 224 cases of neonatal suppurative meningitis with positive cerebrospinal fluid cultures, the highest number of cases occurred in 2018 and the lowest in 2020. The age of onset in newborns exhibited variation, with the highest recorded in 2017 and the lowest in 2021. Bacterial species constituting significant proportions of the etiological distribution were Staphylococcus epidermidis (17.4%), Klebsiella pneumoniae (17.0%), Escherichia coli (15.2%), and Enterococcus faecium (8.0%). Among them, K. pneumoniae showed significant differences in proportion across the years (P = 0.025). Regarding drug-resistant bacteria, carbapenem-resistant Enterobacteriaceae (CRE) and methicillin-resistant coagulase-negative staphylococci (MRCNS) were significantly different between the years (P = 0.016 and P = 0.031, respectively). The highest proportion of drug resistance was observed in MRCNS (22.8%), followed by CRE (16.5%). CONCLUSIONS: The incidence of neonatal suppurative meningitis decreased annually from 2020 to 2022 (following the COVID-19 pandemic). The incidences of Enterococcus faecium was higher before the pandemic, whereas that of MRCNS increased after the epidemic. There were no methicillin-resistant Staphylococcus aureus resistant bacteria after the pandemic. After 2019, the overall incidence of drug-resistant bacteria decreased every year, and the pandemic affected the distribution of pathogens and drug-resistant bacteria.