Pharmacokinetics of Antituberculosis Drugs in Plasma and Cerebrospinal Fluid in a Patient with Pre-Extensive Drug Resistant Tuberculosis Meningitis

Zhilin Liang,1,* Weiming Liao,2,* Qifu Chen,3 Hui Li,1 Meiling Ye,1 Jin Zou,4 Guofang Deng,1 Peize Zhang1 1Department of Pulmonary Medicine & Tuberculosis, The Third People’s Hospital of Shenzhen, National Clinical Research Center for Infectious Disease, Southern University of Science and Technology, Shenzhen, People’s Republic of China; 2Department of Thoracic Oncology, Jiangxi Provincial Cancer Hospital, Nanchang, People’s Republic of China; 3Department of Neurosurgery, The Third People’s Hospital of Shenzhen, National Clinical Research Center for Infectious Disease, Southern University of Science and Technology, Shenzhen, People’s Republic of China; 4Department of Clinical Laboratory, The Third People’s Hospital of Shenzhen, National Clinical Research Center for Infectious Disease, Southern University of Science and Technology, Shenzhen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peize Zhang; Guofang Deng, Tel +8613509650204 ; +8613530027001, Email 82880246@qq.com; jxxk1035@yeah.netAbstract: Drug-resistant tuberculous meningitis (TBM) is the most devastating and critical form of extrapulmonary tuberculosis. Here, we present a case of a 45-year-old male with pre-extensive drug-resistant tuberculosis meningitis (pre-XDR-TBM). He underwent emergency surgery for the long-tunneled external ventricular drainage (LTEVD). Molecular test and phenotypic drug sensitivity test (DST) of Mycobacterium tuberculosis in cerebrospinal fluid (CSF) showed that the isolate was resistant to both rifampin and fluoroquinolones. An anti-tuberculous regimen of isoniazid, pyrazinamide, cycloserine, moxifloxacin, clofazimine, and linezolid was tailored accordingly. We monitored the drug concentration in his plasma and CSF before (at 0-hour) and after anti-TB drugs administration (at 1-hour, 2-hour, 6-hour, and 12-hour) on 10th day after treatment initiation. We hope to provide reference values of drug exposures in plasma and CSF for patients with pre-XDR-TBM.Keywords: pre-extensive drug resistant TB, tuberculous meningitis, pharmacokinetics, long-tunneled external ventricular drain, drug concentration