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Factors Influencing Tuberculosis Treatment Outcome in Adult Patients Treated with Thrice-Weekly Regimens in India.

ABSTRACT: The Indian Revised National Tuberculosis (TB) Control Programme uses thrice-weekly treatment with standard drug dosages. The role of plasma drug levels and other factors in determining TB treatment outcomes is not well understood. We aimed to determine the factors influencing the concentrations of rifampin (RMP), isoniazid (INH), and pyrazinamide (PZA) at 2 h postdosing in adult TB patients and to study the factors impacting TB treatment outcome. We recruited 1,912 adult TB patients (newly treated and retreated patients) with pulmonary/extrapulmonary TB receiving antitubercular treatment (ATT) in the RNTCP in Chennai, India. At steady state, the concentrations of RMP, INH, and PZA were determined at 2 h postdosing after supervised drug administration. A total of 1,648 patients had a favorable outcome, while 264 (14%) had an unfavorable outcome. A total of 91%, 16%, and 17% of the patients had suboptimal concentrations of RMP (<8 ?g/ml), INH (<3 ?g/ml), and PZA (<20 ?g/ml), respectively. Factors associated with treatment outcome were low RMP concentrations (adjusted odds ratio [aOR], 0.94; 95% confidence interval [CI], 0.89 to 0.99; P = 0.036), category II ATT (aOR, 2.39; 95% CI, 1.56 to 3.65; P < 0.001), low body weight (aOR, 0.96; 95% CI, 0.94 to 0.98; P < 0.001), alcohol use (aOR, 2.17; 95% CI, 1.42 to 3.31; P < 0.001), male gender (aOR, 1.92; 95% CI, 1.02 to 3.62; P = 0.043), and baseline INH resistance (aOR, 5.74; 95% CI, 3.12 to 10.59; P < 0.001), which significantly increased the likelihood of an unfavorable outcome in multivariate logistic regression analysis. Further studies are needed to optimize anti-TB drug dosages and improve cure rates. Drug susceptibility testing at the baseline and attention to undernutrition and alcohol dependence are other important interventions.

SUBMITTER: Ramachandran G

PROVIDER: S-EPMC5404592 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Factors Influencing Tuberculosis Treatment Outcome in Adult Patients Treated with Thrice-Weekly Regimens in India.

Ramachandran Geetha G Agibothu Kupparam Hemanth Kumar HK Vedhachalam Chandrasekaran C Thiruvengadam Kannan K Rajagandhi Vijayalakshmi V Dusthackeer Azger A Karunaianantham Ramesh R Jayapal Lavanya L Swaminathan Soumya S

Antimicrobial agents and chemotherapy 20170424 5

The Indian Revised National Tuberculosis (TB) Control Programme uses thrice-weekly treatment with standard drug dosages. The role of plasma drug levels and other factors in determining TB treatment outcomes is not well understood. We aimed to determine the factors influencing the concentrations of rifampin (RMP), isoniazid (INH), and pyrazinamide (PZA) at 2 h postdosing in adult TB patients and to study the factors impacting TB treatment outcome. We recruited 1,912 adult TB patients (newly treat ...[more]

PMID: 28242663

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Project description:BackgroundShortening tuberculosis (TB) treatment duration is a research priority. This paper presents data from a prematurely terminated randomized clinical trial, of 4-month moxifloxacin or gatifloxacin regimens, in South India.MethodsNewly diagnosed, sputum-positive HIV-negative pulmonary TB patients were randomly allocated to receive gatifloxacin or moxifloxacin, along with isoniazid and rifampicin for 4 months with pyrazinamide for first 2 months (G or M) or isoniazid and rifampicin for 6 months with ethambutol and pyrazinamide for first 2 months (C). All regimens were administered thrice-weekly. Clinical and bacteriological assessments were done monthly during treatment and for 24 months post-treatment. The Data and Safety Monitoring Board recommended termination of the trial due to high TB recurrence rates in the G and M regimens.ResultsOf 416 patients in intent-to-treat analysis, 6 (5%) of 124, 2 (2%) of 110 and 2 (2%) of 137 patients with drug-susceptible TB in the G, M and C arms respectively had unfavorable response at the end of treatment; during the next 24 months, 17 (15%) of 115, 11 (11%) of 104 and 8 (6%) of 132 patients respectively, had TB recurrence. Of 38 drug-resistant patients 1 of 8 and 3 of 26 in the G and C arms respectively had unfavourable response at the end of treatment; and TB recurrence occurred in 2 of 7 and 2 of 23 patients, respectively. The differences in TB recurrence rates between the G and C arms was statistically significant (p = 0.02). Gastro-intestinal symptoms occurred in 23%, 22% and 9% of patients in the G, M and C arms respectively, but most reactions were mild and manageable with symptomatic measures; 1% required regimen modification.Conclusions4-month thrice-weekly regimens of gatifloxacin or moxifloxacin with isoniazid, rifampicin and pyrazinamide, were inferior to standard 6-month treatment, in patients with newly diagnosed sputum positive pulmonary TB.Trial registrationClinical Trials Registry of India CTRI/2012/10/003060.

Project description:Residual kidney function (RKF) contributes to improved survival in hemodialysis (HD) patients. However, it is not clear whether RKF allows a comparable survival rate in patients undergoing twice-weekly HD compared with thrice-weekly HD.We enrolled 685 patients from a prospective multicenter observational cohort. RKF and HD adequacy was monitored regularly over 3-year follow-up. Patients with RKF were divided into groups undergoing twice-weekly HD (n = 113) or thrice-weekly HD (n = 137). Patients without RKF undergoing thrice-weekly HD (n = 435) were included as controls. Fluid balance and dialysis-associated characteristics were followed and clinical outcomes evaluated using all-cause mortality and cardiovascular events (CVE).In patients with RKF, baseline and follow-up RKF were significantly higher in patients undergoing twice-weekly HD than in those undergoing thrice-weekly HD. Total Kt/V urea (dialysis plus residual renal) in patients with RKF undergoing twice-weekly HD was greater than or equal to those in patients with or without RKF undergoing thrice-weekly HD. Compared with patients with RKF undergoing thrice-weekly HD, patients with RKF undergoing twice-weekly HD had no fluid excess, but their normalized protein catabolic rate became lower since 24-month follow up. In multivariable analyses, patients with RKF undergoing twice-weekly HD had a noninferior risk of mortality (hazard ratio [HR], 0.83; 95% confidence interval [95% CI], 0.34-2.01, P = 0.68) and of CVE (HR, 0.60; 95% CI, 0.28-1.29, P = 0.19) compared with patients without RKF undergoing thrice-weekly HD. However, this group showed an independent association with a greater risk of mortality compared with patients with RKF undergoing thrice-weekly HD (HR, 4.20; 95% CI, 1.02-17.32, P = 0.04).In conclusion, patients with RKF undergoing twice-weekly HD had an increased risk of mortality compared with those undergoing thrice-weekly HD. Decisions about twice-weekly HD should consider not only RKF, but also other risk factors such as normalized protein catabolic rate.

Project description:BackgroundWeekly rifapentine and isoniazid (3HP) is gaining popularity for latent tuberculosis infection treatment because of its short course and high completion rate. Prior to widespread use, comprehensive 3HP treatment assessment covering an all-age population is essential.MethodsParticipants receiving ≥1 3HP dose from September 2014 to December 2019 were stratified into elderly (≥65 years), middle-aged (>35 & <65 years), and younger (≤35 years) age groups. This study investigated the impact of age on treatment outcome, particularly systemic drug reactions (SDRs) and 3HP discontinuation.ResultsOverall, 134 of 579 (23.1%) participants were elderly. The completion rate was 83.1% overall and was highest and lowest in the younger group (94.5%) and elderly (73.9%) group, respectively. However, the 3HP discontinuation rate was not significantly different among the 3 groups in multivariate logistic regression analysis. In total, 362 (62.5%) participants experienced 1 or more adverse drug reactions (ADRs), of which 38 (10.5%) and 98 (27.1%) required temporary and permanent treatment interruption, respectively. The SDR risk was 11.2% in overall and 17.1% in the middle-aged group, 3.04-fold higher than that in the elderly group (P = .025). This finding was consistently observed in different clinical settings. Hypertensive events accompanied with flu-like symptoms occurred in 11.2% of elderly participants, and accounted for 50% of grade ≥3 ADRs.ConclusionsWith proper medical support and programmatic follow-up, the 3HP completion rate is >70% even in elderly participants. In middle-aged and elderly individuals, 3HP should be employed with caution because of risk of SDRs and hypertensive events, respectively. Summary: Under programmatic medical support, widespread use of weekly rifapentine and isoniazid (3HP) for latent tuberculosis treatment is possible for its high completion rate. 3HP should be employed with caution for risk of systemic drug reactions and hypertensive events in middle-aged and elderly individuals, respectively.

Dataset Information

Factors Influencing Tuberculosis Treatment Outcome in Adult Patients Treated with Thrice-Weekly Regimens in India.

Publications

Factors Influencing Tuberculosis Treatment Outcome in Adult Patients Treated with Thrice-Weekly Regimens in India.

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