Pharmacokinetics of Second-Line Antituberculosis Drugs in Children with Multidrug-Resistant Tuberculosis in India.

We studied the pharmacokinetics of levofloxacin (LFX), pyrazinamide (PZA), ethionamide (ETH), and cycloserine (CS) in children with multidrug-resistant tuberculosis (MDR-TB) who were being treated according to the Revised National TB Control Programme (RNTCP) guidelines in India. This observational, pharmacokinetic study was conducted in 25 children with MDR-TB at the Sarojini Naidu Medical College, Agra, India, who were being treated with a 24-month daily regimen. Serial blood samples were collected after directly observed administration of drugs. Estimations of plasma LFX, PZA, ETH, and CS were undertaken according to validated methods by high-performance liquid chromatography. Adverse events were noted at 6 months of treatment. The peak concentration (Cmax) of LFX was significantly higher in female than male children (11.5 µg/ml versus 7.3 µg/ml; P = 0.017). Children below 12 years of age had significantly higher ETH exposure (area under the concentration-time curve from 0 to 8 h [AUC0-8]) than those above 12 years of age (17.5 µg/ml · h versus 9.4 µg/ml; P = 0.030). Multiple linear regression analysis showed significant influence of gender on Cmax of ETH and age on Cmax and AUC0-8 of CS. This is the first and only study from India reporting on the pharmacokinetics of LFX, ETH, PZA, and CS in children with MDR-TB treated in the Government of India program. More studies on the safety and pharmacokinetics of second-line anti-TB drugs in children with MDR-TB from different settings are required.

Urinary excretion of metformin in diabetic patients with and without tuberculosis.

BACKGROUND: Patients with concurrent diabetes mellitus (DM) and tuberculosis (TB) pose an increased risk of treatment failure in TB and management of DM is complicated. Anti-diabetic and anti-TB drugs may interact with on another other when co-administered. The role of anti-TB drugs on the excretion of metformin in urine has not been studied. Therefore, we carried out a study in DM patients with and without TB to compare the percentage of metformin excreted in urine. METHODS: A total of 52 DMTB and 17 DM patients were recruited in this study from the Chennai Corporation Centres. DM and DM - TB patients were administered the prescribed anti-TB and anti-diabetic drugs (metformin (MET), glipizide (GLP),glimepiride (GLM),glibenclamide (GLB),rifampicin (RMP),isoniazid (INH), pyrazinamide (PZA) and ethambutol (EMB). DM and DMTB patients received metformin (MET) alone and in combination with sulphonylureas as diabetic drugs. The urine samples were collected from 0 to 8 hours after drug administration. Urine MET excreted in DM and DMTB patients were estimated by high performance liquid chromatography (HPLC) and percent dose was calculated. RESULTS: The percent dose of MET excreted in urine in DMTB patients was significantly higher when compared to DM patients. There is significant difference in the percent dose of MET excreted among DM patients with and without sulphonylureas, values being 23.3 and 17.7% respectively (p = 0.044). CONCLUSION: This is the first study to report on the percent dose of MET excretion in urine in patients with DM and DMTB receiving MET along with anti-TB drugs.

Association of Tuberculosis With Household Catastrophic Expenditure in South India.

Importance: The high household costs associated with tuberculosis (TB) diagnosis and treatment can create barriers to access and adherence, highlighting the urgency of achieving the World Health Organization's End TB Strategy target that no TB-affected households should face catastrophic costs by 2020. Objective: To estimate the occurrence of catastrophic costs associated with TB diagnosis and treatment and to identify socioeconomic indicators associated with catastrophic costs in a setting where TB control strategies have been implemented effectively. Design, Setting, and Participants: In this cross-sectional study, 455 patients with TB in the Chennai metropolitan area of South India who were treated under the TB control program between February 2017 and March 2018 were interviewed. Patients were interviewed by trained field investigators at 3 time points: at the initiation of treatment, at the end of the intensive phase of treatment, and at the end of the continuation phase of treatment. A precoded interview schedule was used to collect information on demographic, socioeconomic, and clinical characteristics and direct medical, direct nonmedical, and indirect costs. Data analysis was performed from August 2018 to November 2019. Main Outcomes and Measures: Direct, indirect, and total costs to patients with TB. Catastrophic costs associated with TB were defined as costs exceeding 20% of the household's annual income. A binary response model was used to determine the factors that were significantly associated with catastrophic costs. Results: Of 455 patients with TB interviewed, 205 (53%) were aged 19 to 45 years (mean [SD] age, 38.4 [16.0] years), 128 (33%) were female, 72 (19%) were illiterate, 126 (33%) were employed, and 186 (48%) had a single earning member in the family (percentages are based on the 384 patients who were interviewed through the end of the continuation phase of treatment). Sixty-one percent of patients (234 patients) had pulmonary smear positive TB. The proportion of patients with catastrophic costs was 31%. Indirect costs contributed more toward catastrophic cost than did direct costs. Multivariate logistic regression analysis found that unemployment (adjusted odds ratio, 0.2; 95% CI, 0.1-0.5; P < .001) and higher annual household income (Rs 1-200 000, adjusted odds ratio, 0.4; 95% CI, 0.2-0.7; P = .004; Rs >200 000, adjusted odds ratio, 0.2; 95% CI, 0.1-0.5; P < .001) were associated with a decreased likelihood of experiencing catastrophic costs. Conclusions and Relevance: Despite the implementation of free diagnostic and treatment services under a national TB control program, TB-affected households had a high risk of catastrophic costs and further impoverishment. There is an urgent demand to provide additional financial protection for patients with TB.

Catastrophic costs due to tuberculosis in South India: comparison between active and passive case finding.

BACKGROUND: To measure and compare economic burden at the household level for tuberculosis (TB) patients who were detected through active case finding (ACF) and passive case finding (PCF) in rural areas. METHODS: This study was conducted in the Thiruvallur district from October 2016 to March 2018. TB patients diagnosed through ACF were included in this study. For the comparison, patients diagnosed through ACF were recruited in the ratio of 1:2 from the same study area during the same period. Costs between the groups were compared and a multiple regression model was used to identify factors associated with catastrophic costs due to TB. RESULTS: Of the 336 individuals, 110 were diagnosed through ACF and 226 through PCF. A total of 29% of patients diagnosed through PCF and 9% of patients diagnosed through ACF experienced catastrophic costs due to TB. The multiple logistic model shows that catastrophic costs due to TB had a significant association with higher income status (adjusted odds ratio [aOR] 4.91 [confidence interval {CI} 2.39 to 10.08]; p<0.001), alcohol use (aOR 2.78 [CI 1.33 to 5.81]; p=0.007), private as a first point of care (aOR 3.91 [CI 2.01 to 7.60]; p<0.001) and PCF (aOR 3.68 [CI 1.62 to 8.33]; p=0.002). CONCLUSIONS: Findings highlight that ACF significantly averted catastrophic costs due to TB among patients. ACF as a strategy could ensure financial protection of TB patients and limit their risk of poverty.

Adequacy of examining one sputum specimen in tuberculosis drug resistance surveys.

OBJECTIVE/BACKGROUND: Collection of one spot and one morning sputum specimen is recommended for tuberculosis (TB) drug resistance surveys. This was a retrospective analysis of Mycobacterium tuberculosis cultures isolated from two spot sputum specimens collected from smear positive TB patients in a TB drug resistance survey. It was conducted to understand the value of a second specimen. METHODS: A TB drug resistance survey was conducted in the state of Tamil Nadu, India, to estimate the prevalence of drug resistance among new sputum smear-positive (NSP) and previously treated (PT) patients diagnosed in Revised National Tuberculosis Control Program microscopy centers. A total of 2425 patients (1524 NSP and 901 PT cases) were enrolled in the study. From these patients, two spot sputum specimens (C and D) were collected within a period of 2h. No preservative was added to sputum. The samples were transported at ambient conditions without cold storage to the central laboratory for culture of M. tuberculosis. Culture yield from each sample was computed and analyzed. RESULTS: The proportion of cultures retrieved from C and D specimens among NSP cases (89.3% and 89.7%) and PT cases (90.8% and 90.3%) were similar. The culture grades of C and D samples were comparable (chi-square test, 3560.135; p<.001) and the agreement was moderate (kappa test, 0.454). CONCLUSION: The findings of the study reveal the adequacy of single spot sputum specimen from smear positive pulmonary TB patients for bacteriological examination in a quality-assured TB laboratory to determine precisely the level of drug resistance in a province of India.