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Neurosurgical patients are considered to be at higher risk for infections including nosocomial infections compared with other critically ill individuals. Empirical antimicrobial therapy is of utmost importance for the survival of infected neurosurgical patients. The microbial distribution and antimicrobial resistance patients from January 2012 to December 2021 (10 years) were analyzed retrospectively. Identification was done using VITEK-2 and MALDI-TOF systems. Antimicrobial susceptibility testing was determined by the Kirby Bauer Disk Diffusion Agar method (Clinical and Laboratory Standards Institute) and VITEK-2. A total of 48,474 samples were received, out of which 10,134 (21%) had growth. Respiratory specimens showed the maximum isolation of pathogens (42% n = 4292). The predominant bacterial pathogens were gram negative (n = 8972; 88.5%), whereas gram positives were only 11.5% (n = 1162) of the total organisms. Among the gram positives, the most common was Staphylococcus aureus (64.6%), and among gram negatives, the most common pathogen was Acinetobacter baumanni (38.6%). The weighted average of the drug-resistance profile across all gram positives was >50% for fluoroquinolones (levofloxacin, ciprofloxacin), gentamicin, erythromycin, and ampicillin, and in the case of gram negatives it was >90% for ampicillin-sulbactam, ticarcillin, cefazolin, cefotaxime, and ceftriaxone. Thirty-two patients were found to have candidemia, out of which 6 were C. albicans and the rest were nonalbican. Six neurosurgery patients had infection with C. auris , 4 from blood samples and 2 from urine. This study will add to the current knowledge and provide a better understanding of pathogen profile and resistance patterns in traumatic brain injury patients. [ABSTRACT FROM AUTHOR]