title: Long-term Mortality of Patients With Tuberculous Meningitis in New York City: A Cohort Study.
abstract: Tuberculous meningitis (TBM) is the most devastating clinical presentation of infection with Mycobacterium tuberculosis; delayed initiation of effective antituberculosis therapy is associated with poor treatment outcomes. Our objective was to determine the relationship between drug resistance and 10-year mortality among patients with TBM.
  
  
  
  We conducted a retrospective cohort study of 324 patients with culture-confirmed TBM, susceptibility results reported for isoniazid and rifampin, and initiation of at least 2 antituberculosis drugs, reported to the tuberculosis registry in New York City between 1 January 1992 and 31 December 2001. Date of death was ascertained by matching the tuberculosis registry with death certificate data for 1992-2012 from the New York Office of Vital Statistics. Human immunodeficiency virus (HIV) status was ascertained by medical records review, matching with the New York City HIV Surveillance registry, and review of cause of death.
  
  
  
  Among 257 TBM patients without rifampin-resistant isolates, isoniazid resistance was associated with mortality after the first 60 days of treatment when controlling for age and HIV infection (adjusted hazard ratio, 1.94 [95% confidence interval, 1.08-3.94]). Death occurred before completion of antituberculosis therapy in 63 of 67 TBM patients (94%) with rifampin-resistant disease.
  
  
  
  Among patients with culture-confirmed TBM, we observed rapid early mortality in patients with rifampin-resistant isolates, and an independent association between isoniazid-resistant isolates and death after 60 days of therapy. These findings support the continued evaluation of rapid diagnostic techniques and the empiric addition of second-line drugs for patients with clinically suspected drug-resistant TBM.
authors.affiliation: Public Health Research Institute, New Jersey Medical School, Newark, New Jersey, USA
authors.forename: Christopher
authors.initials: C
authors.lastname: Vinnard
authors.affiliation: New York City Department of Health and Mental Hygiene, Bureau of Tuberculosis Control, Queens, NY, USA.
authors.forename: Liza
authors.initials: L
authors.lastname: King
authors.affiliation: University of Rochester School of Medicine and Dentistry, New York, USA.
authors.forename: Sonal
authors.initials: S
authors.lastname: Munsiff
authors.affiliation: New York City Department of Health and Mental Hygiene, Bureau of Tuberculosis Control, Queens, NY, USA.
authors.forename: Aldo
authors.initials: A
authors.lastname: Crossa
authors.affiliation: Division of Infectious Disease Therapeutics, Kobe University, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Iwata
authors.affiliation: Center for Infectious Disease Research and Experimental Therapeutics, Baylor University, Dallas, Texas, USA.
authors.forename: Jotam
authors.initials: J
authors.lastname: Pasipanodya
authors.affiliation: New York City Department of Health and Mental Hygiene, Bureau of Tuberculosis Control, Queens, NY, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Proops
authors.affiliation: New York City Department of Health and Mental Hygiene, Bureau of Tuberculosis Control, Queens, NY, USA.
authors.forename: Shama
authors.initials: S
authors.lastname: Ahuja
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000302:isolation & purification; D009519:New York City / Q000453:epidemiology; D012189:Retrospective Studies; D012293:Rifampin / Q000494:pharmacology; D013997:Time Factors; D014390:Tuberculosis, Meningeal / Q000401:mortality*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid; D012293:Rifampin
keywords: drug resistance; multidrug resistance; treatment outcome; tuberculosis; tuberculous meningitis