Long-term Mortality of Patients With Tuberculous Meningitis in New York City: A Cohort Study

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: drug resistance; multidrug resistance; treatment outcome; tuberculosis; tuberculous meningitis.

Figure 1.

Annual number of patients with culture-confirmed tuberculous meningitis in New York City, 1992–2001 (N = 324), according to HIV status and isoniazid susceptibility. Year of diagnosis corresponds to the date that the first positive cerebrospinal fluid culture was collected. ^*Nonparametric test for trend in the proportion of tuberculous meningitis patients coinfected with HIV. Abbreviations: HIV, human immunodeficiency virus; INH-R, isoniazid resistant; INH-S, isoniazid sensitive; TBM, tuberculous meningitis.

Figure 2.

Kaplan-Meier survival curves of patients with culture-confirmed tuberculous meningitis, susceptibility reported for isoniazid and rifampin, initiating antituberculosis treatment with ≥2 drugs. A, Overall. B, Stratified by HIV status. C, Stratified by drug susceptibility patterns. *Statistical comparison of survival curves with log-rank test. Abbreviations: HIV, human immunodeficiency virus; INH-R, isoniazid resistant; INH-S, isoniazid sensitive; MDR, multidrug resistant; RIF-R, rifampin resistant; RIF-S, rifampin sensitive; TBM, tuberculous meningitis.

Figure 3.

Long-term survival of 117 patients with tuberculous meningitis (TBM) who successfully completed therapy, compared with age- and sex-matched population controls. A, Human immunodeficiency virus (HIV)–uninfected survivors of TBM (n = 65). B, HIV-infected survivors of TBM (n = 52).