Background: Study aims to determine the bacterial profile associated with bacterial meningitis, their antimicrobial resistance pattern providing antimicrobial stewardship guidance and improving the efficacy of empirical treatment. Methods: Four years case-series retrospective study (December 2019- December 2023), of positive CSF cultures in 432 patients of various age groups and departments in Ain Shams University Hospital, Cairo, Egypt were analyzed. Results: Predominance of Gram-negative bacteria constituting 79.1%, while 19.6% were attributed to gram-positive in bacterial meningitis. Notably, Klebsiella pneumoniae (K. pneumoniae) had the highest prevalence at 34%, followed by Acinetobacter species (spp) at 19.6%. Whereas, Streptococcus pneumoniae (S. pneumonia) exhibited a lower prevalence of 1.8%. The age group >16-50 years demonstrated the highest prevalence at 26.6%, followed by infants aged 2 months to <1 year, with a prevalence of 23.3%. Antimicrobial resistance was predominantly against ceftriaxone 89%, and ampicillin 87.9%. Conversely, pathogens exhibited greater sensitivity to tobramycin (46.2%) and gentamicin (43.1%) than other antimicrobials. Multidrug resistance was identified in 53.5% of Gram-negative bacteria. These results highlight Gram-negative bacteria role in meningitis. Conclusion: This study revealed significant changes in meningitis bacterial profiles, highlighting the importance of reinforcing antimicrobial stewardship efforts to effectively combat the evolving landscape of bacterial meningitis.