Document Detail


Influence of antituberculosis drug resistance and Mycobacterium tuberculosis lineage on outcome in HIV-associated tuberculous meningitis.
MedLine Citation:
PMID:  22470117     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
HIV-associated tuberculous meningitis (TBM) has high mortality. Aside from the devastating impact of multidrug resistance (MDR) on survival, little is understood about the influence of other bacterial factors on outcome. This study examined the influence of Mycobacterium tuberculosis drug resistance, bacterial lineage, and host vaccination status on outcome in patients with HIV-associated TBM. Mycobacterium tuberculosis isolates from the cerebrospinal fluid of 186 patients enrolled in two studies of HIV-associated TBM in Ho Chi Minh City, Vietnam, were tested for resistance to first-line antituberculosis drugs. Lineage genotyping was available for 122 patients. The influence of antituberculosis drug resistance and M. tuberculosis lineage on 9-month mortality was analyzed using Kaplan-Meier survival analysis and Cox multiple regression models. Isoniazid (INH) resistance without rifampin resistance was associated with increased mortality (adjusted hazard ratio [HR], 1.78, 95% confidence interval [CI], 1.18 to 2.66; P = 0.005), and multidrug resistance was uniformly fatal (n = 8/8; adjusted HR, 5.21, 95% CI, 2.38 to 11.42; P < 0.0001). The hazard ratio for INH-resistant cases was greatest during the continuation phase of treatment (after 3 months; HR, 5.05 [95% CI, 2.23 to 11.44]; P = 0.0001). Among drug-susceptible cases, patients infected with the "modern" Beijing lineage strains had lower mortality than patients infected with the "ancient" Indo-Oceanic lineage (HR, 0.29 [95% CI, 0.14 to 0.61]; P = 0.001). Isoniazid resistance, multidrug resistance, and M. tuberculosis lineage are important determinants of mortality in patients with HIV-associated TBM. Interventions which target these factors may help reduce the unacceptably high mortality in patients with TBM.
Authors:
Dau Quang Tho; M Estée Török; Nguyen Thi Bich Yen; Nguyen Duc Bang; Nguyen Thi Ngoc Lan; Vo Sy Kiet; Nguyen van Vinh Chau; Nguyen Huy Dung; Jeremy Day; Jeremy Farrar; Marcel Wolbers; Maxine Caws
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2012-04-02
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  56     ISSN:  1098-6596     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-05-14     Completed Date:  2012-09-13     Revised Date:  2013-04-15    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3074-9     Citation Subset:  IM    
Affiliation:
Oxford University Clinical Research Unit Vietnam, Wellcome Trust Major Overseas Programme, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
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MeSH Terms
Descriptor/Qualifier:
Adult
Antitubercular Agents / therapeutic use*
Female
Genotype
HIV Infections / drug therapy*,  genetics,  microbiology,  mortality
Humans
Isoniazid / therapeutic use*
Male
Mycobacterium tuberculosis / drug effects*,  pathogenicity*
Rifampin / therapeutic use
Tuberculosis, Meningeal / drug therapy*,  microbiology,  mortality,  virology
Tuberculosis, Multidrug-Resistant / genetics
Young Adult
Grant Support
ID/Acronym/Agency:
//Wellcome Trust
Chemical
Reg. No./Substance:
0/Antitubercular Agents; 13292-46-1/Rifampin; 54-85-3/Isoniazid
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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