Objective To investigate the characteristics of the pathogens isolated from the cerebrospinal fluid (CSF) and the prognosis of the adult patients with central venous system (CNS) infection, and to provide the basis for disease treatment. Methods The clinical data and findings of the laboratory examination of the patients, who were admitted to West China Hospital of Sichuan University from January 2014 to September 2016, and suffered from CNS infection with the positive results of CSF culture, were retrospectively analyzed. The species distribution and in-vitro susceptibility of the pathogens and hospital mortality were analyzed. Results A total of 157 cases, involving 87 (55.4%) community-acquired cases and 70 (44.6%) hospital-acquired cases, were included. One hundred and fifty-eight strains of the pathogens were isolated from the CSF specimens of these patients, including 73 isolates (46.2%) of gram negative bacteria, 64 isolates (40.5%) of fungus, and 21 isolates (13.3%) of gram positive bacteria. In terms of species distribution,Cryptococcus neoformans was the predominant (62/87, 71.3%) species isolated from the patient with community-acquired infection, whileAcinetobacter calcoaceticus-A. baumannii complex (31/71, 43.7%) was the predominant specie from the patients with hospital-acquired infection. Analysis of the resistance phenotypes showed that all theC. neoformans isolates were susceptible to the antifungal agents. More than 90% ofA. calcoaceticus- A. Baumannii complex isolates were resistant to the regular antibiotics. The resistant rates ofK. pneumoniae isolates to the regular antibiotics were no more than 25%. The hospital mortality of the groups infected by gram-negative bacteria, fungi, and gram-positive bacteria were 52.3% (38/72), 32.8% (21/64), and 19.0% (4/21), respectively. There was statistical difference for the hospital mortality among these groups (P=0.006). Conclusion In our hospital,C. neoformans are the common species isolated from CSF of the patients with community-acquired CNS infection. Gram negative bacilli are commonly isolated from CSF of the hospital-acquired cases. The mortality of patients with gram negative bacilli is high.