We reviewed retrospectively the data for adult patients with bacterial meningitis over a period of 10.5 years in our hospital. The clinical characteristics and laboratory data of the 21 cases (52 strains) of mixed infection were analyzed. Two hundred and fifteen cases of single pathogen adult bacterial meningitis (ABM) were also included for comparison. Post-neurosurgical type of ABM was presented in 86% of the mixed infection group. Brain abscess was found in three patients. Fourteen patients survived and seven cases died. The analysis showed a statistical significance for the mixed infection group having a higher rate of nosocomially-acquired, post-neurosurgical condition, hydrocephalus, and lower level of cerebrospinal fluid white cell count, protein and lactate than the single pathogen group. Logistic regression analysis showed the independent factor of “hydrocephalus” (p = 0.002). Presence of hydrocephalus is a significant neuroimaging feature when compared with the single pathogen group. As compared with the previous study results of mixed infection in ABM, the present study showed a change of pathogens implicated of increasing Pseudomonas spp. and Acinetobacter spp. infections, and an emergence of anaerobic pathogens. All these changes deserve special attention because of the need for an appropriate choice of empirical antibiotics and choice of culture method.