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Abstract
The clinical and mycobacterial features of tuberculous meningitis (TBM) cases in China are not well described; especially in western provinces with poor tuberculosis control. We prospectively enrolled patients in whom TBM was considered in Shaanxi Province, northwestern China, over a 2-year period (September 2010 to December 2012). Cerebrospinal fluid specimens were cultured for Mycobacterium tuberculosis; with phenotypic and genotypic drug susceptibility testing (DST), as well as genotyping of all positive cultures. Among 350 patients included in the study, 27 (7.7%) had culture-confirmed TBM; 84 (24.0%) had probable and 239 (68.3%) had possible TBM. DST was performed on 25/27 (92.3%) culture positive specimens; 12/25 (48.0%) had “any resistance” detected and 3 (12.0%) were multi-drug resistant (MDR). Demographic and clinical features of drug resistant and drug susceptible TBM cases were similar. Beijing was the most common genotype (20/25; 80.0%) with 9/20 (45%) of the Beijing strains exhibiting drug resistance; including all 3 MDR strains. All (4/4) isoniazid resistant strains had mutations in the katG gene; 75% (3/4) of strains with phenotypic rifampicin resistance had mutations in the rpoB gene detected by Xpert MTB/RIF®. High rates of drug resistance were found among culture-confirmed TBM cases; most were Beijing strains.
Highlights
® the rpoB gene detected by Xpert MTB/RIF
The fact that nearly half of the Tuberculous meningitis (TBM) patients with positive cerebrospinal fluid (CSF) cultures were infected with a resistant M. tuberculosis strain is alarming
A study from Xijing Hospital in Shaanxi province evaluated a collection of 90 strains, isolated during 2009–2012 from pulmonary tuberculosis cases, and identified multidrug resistant (MDR) in 46.7% (42/90) of isolates; 20% (18/90) were isoniazid mono- and 2.2% (2/90) were rifampin mono-resistant[32]
Summary
® the rpoB gene detected by Xpert MTB/RIF. High rates of drug resistance were found among cultureconfirmed TBM cases; most were Beijing strains. No drug resistance survey has focused on the western parts of China where access to antituberculosis drugs are poorly regulated and tuberculosis disease rates are highest. The detection of specific mutations associated with drug resistance (genotypic DST) may overcome some of the limitations, especially the long time delays, associated with phenotypic DST8. The novel Xpert MTB/RIF assay has the ability to simultaneously detect M. tuberculosis and rpoB gene mutations in a critical 81 base pair region (amino acid 507–533), referred to as the rifampicin-resistance-determining region (RRDR)[10]. The presence of rifampin resistance is highly suggestive of MDR tuberculosis, rifampin mono-resistance is well documented and fairly common in some settings[11]
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