The traditional diagnosis model has great challenges for the etiological diagnosis of the central nervous system (CNS) diseases with similar clinical manifestations, especially for the diagnosis of rare pathogens. It is very important to make rapid and accurate identification of pathogens for guiding clinical choices in administering countermeasures.On August 22, 2020, a 49 years old Chinese male patient had a headache for two days, and then the computed tomography (CT) scan of the brain showed subarachnoid hemorrhage. Subsequently, he underwent twice craniotomy and about 3 weeks of hospitalization. Since September 20, the patient was in the local rehabilitation hospital for hyperbaric oxygen therapy for about three weeks. Then the patient developed acute purulent meningoencephalitis. In the absence of diagnosis of specific pathogenic bacteria, vancomycin (1 g every 12 hours), ceftazidime (2 g every 8 hours), mannitol dehydration (125 mL, every 8 hours), and sodium valproate (0.4 g tid) was used timely according to cerebrospinal fluid (CSF) examination and clinical manifestations. CSF smear and routine culture test were negative during hospitalization. We used the metagenomic next-generation sequencing (mNGS) analysis of CSF for quick and accurate diagnosis, which identified human herpesvirus type 4 (EBV), Corynebacterium corynebacterium, Achromobacter xylose oxidation, and Acinetobacter baumannii, But the mapping degree was not high. Then, we used the modified method-multiplex PCR-based targeted gene sequencing platform (ptNGS) to detect CSF samples and found that the sequences detected were Acinetobacter pittii (A. pittii) and Staphylococcus epidermidis. S. epidermidis might come from skin colonization during lumbar puncture, so it was excluded from the etiological diagnosis. Therefore, we highly suspected that A. pittii was the pathogen in this case. After about three weeks of hospitalization treatment, the patient's symptoms were relieved.In conclusion, empirical medication before the identification of pathogens is very important. The ptNGS may be an effective method for the diagnosis of pathogens.Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.