Clinical Outcomes of Patients With Drug-Resistant Tuberculous Meningitis Treated With an Intensified Antituberculosis Regimen
Background.<br/> 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.<b...
| Main Authors: | , , , , , , , , , , , , |
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| Formato: | Journal article |
| Idioma: | English |
| Publicado: |
Oxford University Press
2017
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| _version_ | 1826278378890592256 |
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| author | Heemskerk, A Nguyen, M Dang, H Vinh Nguyen, C Nguyen, L Do, T Nguyen, T Wolbers, M Day, J Le, T Nguyen, B Caws, M Thwaites, G |
| author_facet | Heemskerk, A Nguyen, M Dang, H Vinh Nguyen, C Nguyen, L Do, T Nguyen, T Wolbers, M Day, J Le, T Nguyen, B Caws, M Thwaites, G |
| author_sort | Heemskerk, A |
| collection | OXFORD |
| description | Background.<br/> 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.<br/><br/> Methods.<br/> 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.<br/><br/> Results.<br/> 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.<br/><br/> Conclusions.<br/> Early intensified treatment improved survival in patients with INH-R TBM. Targeted regimens for drug-resistant TBM should be further explored. |
| first_indexed | 2024-03-06T23:43:02Z |
| format | Journal article |
| id | oxford-uuid:6ff5a5dc-ad4d-4150-905e-40b0b5f1bf42 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:43:02Z |
| publishDate | 2017 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:6ff5a5dc-ad4d-4150-905e-40b0b5f1bf422022-03-26T19:34:04ZClinical Outcomes of Patients With Drug-Resistant Tuberculous Meningitis Treated With an Intensified Antituberculosis RegimenJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6ff5a5dc-ad4d-4150-905e-40b0b5f1bf42EnglishSymplectic Elements at OxfordOxford University Press2017Heemskerk, ANguyen, MDang, HVinh Nguyen, CNguyen, LDo, TNguyen, TWolbers, MDay, JLe, TNguyen, BCaws, MThwaites, GBackground.<br/> 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.<br/><br/> Methods.<br/> 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.<br/><br/> Results.<br/> 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.<br/><br/> Conclusions.<br/> Early intensified treatment improved survival in patients with INH-R TBM. Targeted regimens for drug-resistant TBM should be further explored. |
| spellingShingle | Heemskerk, A Nguyen, M Dang, H Vinh Nguyen, C Nguyen, L Do, T Nguyen, T Wolbers, M Day, J Le, T Nguyen, B Caws, M Thwaites, G Clinical Outcomes of Patients With Drug-Resistant Tuberculous Meningitis Treated With an Intensified Antituberculosis Regimen |
| title | Clinical Outcomes of Patients With Drug-Resistant Tuberculous Meningitis Treated With an Intensified Antituberculosis Regimen |
| title_full | Clinical Outcomes of Patients With Drug-Resistant Tuberculous Meningitis Treated With an Intensified Antituberculosis Regimen |
| title_fullStr | Clinical Outcomes of Patients With Drug-Resistant Tuberculous Meningitis Treated With an Intensified Antituberculosis Regimen |
| title_full_unstemmed | Clinical Outcomes of Patients With Drug-Resistant Tuberculous Meningitis Treated With an Intensified Antituberculosis Regimen |
| title_short | Clinical Outcomes of Patients With Drug-Resistant Tuberculous Meningitis Treated With an Intensified Antituberculosis Regimen |
| title_sort | clinical outcomes of patients with drug resistant tuberculous meningitis treated with an intensified antituberculosis regimen |
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