Tools
Tools
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.
|
Text
Clin_Inf_Dis_cix230_2017.pdf - Published Version Available under License Creative Commons Attribution. Download (381kB) | Preview |
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 |
Statistics
Actions (login required)
 |
Edit Item |