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Clinical Outcomes of Patients With Drug-Resistant Tuberculous Meningitis Treated With an Intensified Antituberculosis Regimen.

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Heemskerk, A Dorothee, Nguyen, Mai Thi Hoang, Dang, Ha Thi Minh, Vinh Nguyen, Chau Van, Nguyen, Lan Huu, Do, Thu Dang Anh, Nguyen, Thuong Thuy Thuong, Wolbers, Marcel, Day, Jeremy, Le, Thao Thi Phuong, Nguyen, Bang Duc, Caws, Maxine ORCID: https://orcid.org/0000-0002-9109-350X and Thwaites, Guy E (2017) 'Clinical Outcomes of Patients With Drug-Resistant Tuberculous Meningitis Treated With an Intensified Antituberculosis Regimen.'. Clinical Infectious Diseases, Vol 65, Issue 1, pp. 20-28.

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Abstract

Drug-resistant tuberculous meningitis (TBM) is difficult to diagnose and treat. Mortality is high and optimal treatment is unknown. We compared clinical outcomes of drug-resistant and -susceptible TBM treated with either standard or intensified antituberculosis treatment. We analyzed the influence of Mycobacterium tuberculosis drug resistance on the outcomes of patients with TBM enrolled into a randomized controlled trial comparing a standard, 9-month antituberculosis regimen (containing rifampicin 10 mg/kg/day) with an intensified regimen with higher-dose rifampicin (15 mg/kg/day) and levofloxacin (20 mg/kg/day) for the first 8 weeks. The primary endpoint of the trial was 9-month survival. In this subgroup analysis, resistance categories were predefined as multidrug resistant (MDR), isoniazid resistant, rifampicin susceptible (INH-R), and susceptible to rifampicin and isoniazid (INH-S + RIF-S). Outcome by resistance categories and response to intensified treatment were compared and estimated by Cox regression. Of 817 randomized patients, 322 had a known drug resistance profile. INH-R was found in 86 (26.7%) patients, MDR in 15 (4.7%) patients, rifampicin monoresistance in 1 patient (0.3%), and INH-S + RIF-S in 220 (68.3%) patients. Multivariable regression showed that MDR (hazard ratio [HR], 5.91 [95% confidence interval {CI}, 3.00-11.6]), P < .001), was an independent predictor of death. INH-R had a significant association with the combined outcome of new neurological events or death (HR, 1.58 [95% CI, 1.11-2.23]). Adjusted Cox regression, corrected for treatment adjustments, showed that intensified treatment was significantly associated with improved survival (HR, 0.34 [95% CI, .15-.76], P = .01) in INH-R TBM. Early intensified treatment improved survival in patients with INH-R TBM. Targeted regimens for drug-resistant TBM should be further explored.

Item Type: Article
Subjects: QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 268 Antitubercular agents. Antitubercular antibiotics
WF Respiratory System > Tuberculosis > WF 200 Tuberculosis (General)
WF Respiratory System > Tuberculosis > WF 360 Drug therapy
WL Nervous System > WL 200 Meninges. Blood-brain barrier
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Clinical Sciences & International Health > International Public Health Department
Digital Object Identifer (DOI): https://doi.org/10.1093/cid/cix230
SWORD Depositor: JISC Pubrouter
Depositing User: JISC Pubrouter
Date Deposited: 26 May 2017 10:44
Last Modified: 15 Jun 2018 14:55
URI: https://archive.lstmed.ac.uk/id/eprint/7099

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