Introduction. In recent years, metagenomic next-generation sequencing (mNGS) has become widely used in medical microbiology to detect pathogen infection. Aim. We aimed to assess the diagnostic performance of mNGS of cerebrospinal fluid (CSF) for prediction of cryptococcal meningitis (CM). Methodology. A comparative evaluation of mNGS (performed on CSF samples) and conventional methods, including India ink staining, culture for fungi and cryptococcal-antigen (CrAg) detection by enzyme immunoassay, was performed on 12 consecutive non-HIV-infected patients with chronic or subacute CM. Results. India ink staining and culture of the CSF were positive for Cryptococcus in 83.33 % (10/12) of the samples; 100 % (11/11) were positive via CrAg EIA. The mNGS results of the CSF identified DNA sequences corresponding to Cryptococcus in 75 % of samples (9/12). However, the DNA of both C. neoformans s.l. and C. gattii s.l. was detected concurrently in 33.33 % (4/12). Conclusion. mNGS is helpful for identifying Cryptococcus species. The application of mNGS, together with India ink staining, culture methods, and CrAg, may significantly improve the diagnostic precision in CM, thereby informing choice of appropriate antifungal treatment courses.

Cryptococcal meningitis (CM) is a relatively common opportunistic infection in patients with human immunodeficiency virus (HIV) infection and can also occur in patients with no underlying disease. The aim of this study was to evaluate the clinical manifestations, laboratory findings, diagnosis and misdiagnosis, treatment, and prognosis of CM at a tertiary care hospital. We performed a retrospective study of 55 patients at a tertiary care hospital from January 1, 1992 to December 31, 2013. All the patients had a definite diagnosis based on etiology. All 55 patients had a positive cerebrospinal fluid (CSF) India ink staining result. The predominant change observed on magnetic resonance imaging (MRI) was leptomeningeal liner enhancement, which is also called 'lumbriciform-enhancing.' Only 15 patients were first diagnosed with CM, indicating a misdiagnosis rate of 72.7%. At the follow-up end point, 8 patients were cured, 33 had improved, and 14 had died. The overall response rate was 74.5%. The voriconazole group had a response rate of 100%, which was significantly higher than the other two groups. Most CM patients in China were previously healthy without any potential risk factors. CM was easily misdiagnosed due to the lack of specificity of early clinical symptoms. Repeated CSF India ink staining should be performed to identify the pathogen. Voriconazole could be administered to the patients with CM, especially to patients who had a treatment failure with amphotericin B alone or accompanied by fluconazole.