Isoniazid and rifampicin heteroresistant Mycobacterium tuberculosis isolated from tuberculous meningitis patients in India.

BACKGROUND: Heteroresistant Mycobacterium tuberculosis (mixture of susceptible and resistant subpopulations) is thought to be a preliminary stage to full resistance and timely detection, initiation of correct treatment is vital for successful anti tubercular therapy. The aim of this study was to detect multi drug resistant (MDR) and heteroresistant M. tuberculosis with the associated gene mutations from patients of tuberculous meningitis. METHODS: A total of 197 M. tuberculosis isolates from 478 patients of TBM were isolated from July 2012 to July 2015 and subjected to drug susceptibility testing (DST) by BACTEC MGIT and Genotype MTBDR line probe assay (LPA). Heteroresistance was defined as presence of both WT and mutant genes in LPA. RESULTS: Of 197 M. tuberculosis isolates, 11 (5.6%) were MDR, 23 (11.6%), 1 (0.5%) were mono resistant to isoniazid (INH) and rifampicin (RMP) respectively. Heteroresistance was detected in 8 (4%), 2 (1%) isolates to INH and RMP respectively. INH heteroresistant strains had WT bands with mutation band S315T1 whereas RMP heteroresistant strains had WT bands with mutation band S531L. CONCLUSION: The prevalence of MDR M. tuberculosis was 5.6% in TBM patients with the most common mutation being ΔWT band with S315T1 for INH and ΔWT band with S531T for RMP. MGIT DST was found to be more sensitive for detecting overall resistance in M. tuberculosis but inclusion of LPA not only reduced time for early initiation of appropriate treatment but also enabled detection of heteroresistance in 8 (4%), 2 (1%) isolates for INH and RMP respectively.

Predictors of adverse outcome in patients of tuberculous meningitis in a multi-centric study from India.

INTRODUCTION: This study aimed to investigate the factors which may predict mortality and neurological disability at one year follow up in patients of tuberculous meningitis (TBM) in India. METHODOLOGY: Patients with TBM were prospectively enrolled from July 2012 to September 2014 from four tertiary care hospitals of Delhi. The demographic characteristics, clinical features and laboratory findings were collected and patients were followed up till 1 year. These were analyzed by univariate and multivariate multinomial logistic regression analysis to identify predictors of adverse patient outcome at 1 year follow up. RESULTS: Out of 478 patients enrolled, 391 patients could be followed up to 1 year. Sixty-four patients (16.3%) died and 150 patients (39%) survived with one or more neurological disability. Altered sensorium, motor deficit, cranial nerve palsy, seizures, isolation of M. tuberculosis and presence of multi-drug resistance were independently associated with any adverse outcome (death or disability) but by multivariate analysis only motor deficit, altered sensorium and isolation of M. tuberculosis on culture produced a statistically significant model for prediction of patient outcome. CONCLUSION: The three-predictor model with motor deficit, altered sensorium and isolation of M. tuberculosis produced a statistically significant model with correct prediction rate of 60.4%. These three variables predicted death with odds ratio of 39.2, 6.7 and 2.1 respectively in comparison to recovery whereas only motor deficit and isolation of M. tuberculosis predicted neurological disability at 1 year with odds ratio of 3.9, 2.4 respectively.