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- Title
Clinical Outcomes of Patients With Drug-Resistant Tuberculous Meningitis Treated With an Intensified Antituberculosis Regimen.
- Authors
Heemskerk, A. Dorothee; Mai Thi Hoang Nguyen; Ha Thi Minh Dang; Chau Van Vinh Nguyen; Lan Huu Nguyen; Thu Dang Anh Do; Thuong Thuy Thuong Nguyen; Wolbers, Marcel; Day, Jeremy; Thao Thi Phuong Le; Nguyen, Bang Duc; Caws, Maxine; Thwaites, Guy E.
- Abstract
Background. 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. Methods. 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. Results. 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. Conclusions. Early intensified treatment improved survival in patients with INH-R TBM. Targeted regimens for drug-resistant TBM should be further explored.
- Subjects
DRUG resistance in bacteria; TUBERCULOUS meningitis; DRUG resistance in microorganisms; RIFAMPIN; ANTITUBERCULAR agents; THERAPEUTICS
- Publication
Clinical Infectious Diseases, 2017, Vol 65, Issue 1, p20
- ISSN
1058-4838
- Publication type
Article
- DOI
10.1093/cid/cix230