scholarly journals Pharmacokinetics of anti-tuberculosis drugs in multidrug resistant tuberculosis patients in India

2020 ◽  
Author(s):  
Kumar AK Hemanth ◽  
PL Natarajan ◽  
T Kannan ◽  
R Sridhar ◽  
S Kumar ◽  
...  
Keyword(s):  
Multivariate Logistic Regression Analysis ◽  
Multidrug Resistant ◽  
Control Programme ◽  
Combination Regimen ◽  
Indian Government ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Drug Concentrations ◽  
Optimal Drug ◽  
Mdr Tb

AbstractProgrammatic Management of multidrug resistant tuberculosis (MDR TB) services were introduced in the Indian TB control programme in 2007. A pharmacokinetic (PK) study of drugs used to treat MDR TB, namely levofloxacin (LFX), ethionamide (ETH), cycloserine (CS), pyrazinamide (PZA), moxifloxacin (MFX) and isoniazid (INH) was undertaken in adult MDR TB patients treated according to the prevailing guidelines in India. Factors influencing drug PK and end-of-intensive phase (IP) status were also determined. We recruited 350 MDR TB patients receiving anti-TB treatment (ATT) in the Indian Government programme in south India. At steady state, serial blood samples were collected, after supervised drug administration. Status at end of IP was noted from the programme records. Of the 303 patients for whom end-of-IP status was known, 214 were culture negative (responders), while 45 patients were either culture positive or required change of regimen or had died before completion of IP (non-responders). The median Cmax (2.0 vs 2.9μg/ml; p = 0.005) and AUC0-12 (12.2 vs 17.0μg/ml.h; p = 0.002) of ETH were significantly lower in non-responders than responders at IP. In multivariate logistic regression analysis, after excluding defaulters and adjusting for confounders, AUC0-12 of ETH significantly influenced end-of-IP status (aOR - 1.065; 95% CI: 1.001 - 1.134; p = 0.047). Drug doses used currently in the programme produced optimal drug concentrations in majority of patients. ETH played a major role in the MDR TB combination regimen and was a key determinant of end-of-IP status.

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

2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Agibothu Kupparam Hemanth Kumar ◽  
Alok Kumar ◽  
Thiruvengadam Kannan ◽  
Rakesh Bhatia ◽  
Dipti Agarwal ◽  
...  
Keyword(s):  
High Performance ◽  
Linear Regression Analysis ◽  
Multidrug Resistant ◽  
Control Programme ◽  
Second Line ◽  
Time Curve ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
The Government

ABSTRACTWe 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 onCmaxof ETH and age onCmaxand AUC0–8of 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.

Health System and Policy Perspectives of Multidrug-resistant Tuberculosis (MDR-TB) Control in India

2017 ◽  
Vol 3 (1) ◽  
pp. 1-15
Author(s):  
Janmejaya Samal
Keyword(s):  
Decision Making ◽  
Surveillance System ◽  
Epidemiological Studies ◽  
Multidrug Resistant ◽  
Control Programme ◽  
Tb Control ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
The Right

Despite the lack of reliable information on multidrug-resistant tuberculosis (MDR-TB) epidemiology, research shows an increasing trend of MDR-TB incidence in India. Of several determinants attributable to the rising trend of MDR-TB, health systems and policy (HSP) determinants play a pivotal role. With this article, an attempt has been made to unravel the HSP challenges for the control of MDR-TB and recommend strategies to overcome that. Ten different strategies have been recommended in this article that includes operations research (OR), molecular epidemiological studies, drug susceptibility test (DST), surveillance system, advocacy communication and social mobilisation (ACSM), nutrition and livelihood support, contribution of private practitioners (PPs), human resources for health (HRH), social determinants of health and information systems. Methods of OR with the right technical expertise can help in decision-making and evaluation of the TB control programme. Molecular epidemiological studies further help identify the right strain and can help in institutionalising the right therapeutic regimen. Similarly, the DST allows extended treatment strategies, including second-line drugs. A proper surveillance system can enable the availability of the right information for public health decision-making. Communication enables and empowers the community in accessing health services and helps policymakers take informed decisions. Nutrition and livelihood support are essential in TB control as it mostly affects the poor and people in the productive age group. Further, tapping PPs is equally important as more than 50 per cent of TB patients visit them. Proper orientation of the PPs about the TB control programme is non-negotiable given these facts. The HRH issues are pertinent—staff members lack the required motivation owing to delay in payment of salaries and the lack of job promotion. The HRH form the backbone of any health system, as the mere presence of drugs, technologies and infrastructure do not suffice for the provision of healthcare. Attention on the neglected social determinants of health is required as well. Finally, all these suggestions need to be implemented in coordination with each other to bring down the scourge of MDR-TB in India.

scholarly journals Plasma Drug Activity in Patients on Treatment for Multidrug-Resistant Tuberculosis

2013 ◽  
Vol 58 (2) ◽  
pp. 782-788 ◽  
Author(s):  
Stellah G. Mpagama ◽  
Norah Ndusilo ◽  
Suzanne Stroup ◽  
Happiness Kumburu ◽  
Charles A. Peloquin ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Multidrug Resistant ◽  
Plasma Drug ◽  
Content Type ◽  
Drug Activity ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Drug Concentrations ◽  
Mdr Tb ◽  
Time To Detection

ABSTRACTLittle is known about plasma drug concentrations relative to quantitative susceptibility in patients with multidrug-resistant tuberculosis (MDR-TB). We previously described a TB drug activity (TDA) assay that determines the ratio of the time to detection of plasma-coculturedMycobacterium tuberculosisversus control growth in a Bactec MGIT system. Here, we assess the activity of individual drugs in a typical MDR-TB regimen using the TDA assay. We also examined the relationship of the TDA to the drug concentration at 2 h (C2) and the MICs among adults on a MDR-TB regimen in Tanzania. These parameters were also compared to the treatment outcome of sputum culture conversion. Individually, moxifloxacin yielded superior TDA results versus ofloxacin, and only moxifloxacin and amikacin yielded TDAs equivalent to a −2-log killing. In the 25 patients enrolled on a regimen of kanamycin, levofloxacin, ethionamide, pyrazinamide, and cycloserine, theC2values were found to be below the expected range for levofloxacin in 13 (52%) and kanamycin in 10 (40%). Three subjects with the lowest TDA result (<1.5, a finding indicative of poor killing) had significantly lower kanamycinC2/MIC ratios than subjects with a TDA of ≥1.5 (9.8 ± 8.7 versus 27.0 ± 19.1;P= 0.04). The mean TDAs were 2.52 ± 0.76 in subjects converting to negative in ≤2 months and 1.88 ± 0.57 in subjects converting to negative in >2 months (P= 0.08). In Tanzania, MDR-TB drug concentrations were frequently low, and a wide concentration/MIC range was observed that affected plasma drug activityex vivo. An opportunity exists for pharmacokinetic optimization in current MDR-TB regimens, which may improve treatment response.

scholarly journals Predictors of Multidrug-Resistant Tuberculosis (MDR-TB) in Sudan

Antibiotics ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 90 ◽  
Author(s):  
Monadil H. Ali ◽  
Alian A. Alrasheedy ◽  
Mohamed Azmi Hassali ◽  
Dan Kibuule ◽  
Brian Godman
Keyword(s):  
Treatment Failure ◽  
Rural Areas ◽  
Multivariate Logistic Regression Analysis ◽  
Previous Treatment ◽  
Multidrug Resistant ◽  
Global Public Health ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Validated Questionnaire ◽  
Mdr Tb

Multidrug-resistant tuberculosis (MDR-TB) is a global public health threat and burden on the health system. This is especially the case in high tuberculosis (TB) prevalence countries, such as Sudan. Consequently, this study aimed to ascertain the predictors of MDR-TB in Sudan to provide future guidance. An unmatched case-control study to assess the predictors of MDR-TB infections among the Sudanese population was conducted from August 2017 to January 2018 at Abu-Anga referral hospital. Patients’ data was gathered from patients’ cards and via interviews. A structured pre-validated questionnaire was used to gather pertinent information, which included sociodemographic characteristics and other relevant clinical data. Univariate and multivariate logistic regression analysis was employed to determine the predictors of MDR-TB infection. 76 of the 183 patients interviewed (41.5%) had MDR-TB cases. The independent predictors for MDR-TB were living in rural areas [adjusted odds ratio (aOR) = 3.1 (95% confidence interval (CI): 1.2–8.2)], treatment failure [aOR = 56.9 (10.2–319.2)], and smoking [(aOR = 4 (1.2–13.2)], whereas other sociodemographic factors did not predict MDR-TB. In conclusion, the study showed that a history of smoking, living in rural areas, and a previous treatment failure were the predictors of MDR-TB in Sudan. The latter factors are most likely due to issues that are related to access and adherence to treatment and lifestyle. The existence of any of these factors among newly diagnosed TB patients should alert clinicians for the screening of MDR-TB. The implementation of directly observed treatment (DOT) and health education are crucial in stopping the spread of MDR-TB in Sudan.

scholarly journals Effect of Combinations of Mycobacteriophages and Drugs against Mycobacterium Spp.

2020 ◽  
pp. 1-19
Author(s):  
Rajitha Satish ◽  
Anita Desouza
Keyword(s):  
Multidrug Resistant ◽  
Inhibitory Effect ◽  
Dilution Method ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Drug Concentrations ◽  
Alternative Approach ◽  
Mdr Tb ◽  
Dye Reduction

The emergence of multidrug-resistant tuberculosis (MDR-TB) is a matter of global concern. The use of mycobacteriophages alone or in combination with antibiotics could be used as an alternative approach to treat drug-resistant Mycobacteria. The aim of the study was the evaluation of the effect of an isolated mycobacteriophage in combination with Isoniazid, Rifampicin, Streptomycin, and Ampicillin against Mycobacterium tuberculosis and Mycobacterium smegmatis. Determination of the MIC of the above drugs for each strain was done by the standard tube dilution method. Further, the inhibitory effect of varying drug concentrations in combination with different dilutions of the mycobacteriophage was studied. The growth inhibition pattern for both the organisms was also studied in the presence of different dilutions of mycobacteriophage by turbidometric and resazurin dye reduction method. The killing pattern of drugs, at concentrations below the MIC, when combined with mycobacteriophage, was determined. The phage induced lysis of bacteria assisted in decreasing the inhibitory concentration of the drugs.

scholarly journals The epidemiologic impact and cost-effectiveness of new tuberculosis vaccines on multidrug-resistant tuberculosis in India and China

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Chathika K Weerasuriya ◽  
Rebecca C Harris ◽  
C Finn McQuaid ◽  
Fiammetta Bozzani ◽  
Yunzhou Ruan ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Cost Effective ◽  
Multidrug Resistant ◽  
Second Line ◽  
Second Line Therapy ◽  
China And India ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Line Therapy ◽  
Mdr Tb

Abstract Background Despite recent advances through the development pipeline, how novel tuberculosis (TB) vaccines might affect rifampicin-resistant and multidrug-resistant tuberculosis (RR/MDR-TB) is unknown. We investigated the epidemiologic impact, cost-effectiveness, and budget impact of hypothetical novel prophylactic prevention of disease TB vaccines on RR/MDR-TB in China and India. Methods We constructed a deterministic, compartmental, age-, drug-resistance- and treatment history-stratified dynamic transmission model of tuberculosis. We introduced novel vaccines from 2027, with post- (PSI) or both pre- and post-infection (P&PI) efficacy, conferring 10 years of protection, with 50% efficacy. We measured vaccine cost-effectiveness over 2027–2050 as USD/DALY averted-against 1-times GDP/capita, and two healthcare opportunity cost-based (HCOC), thresholds. We carried out scenario analyses. Results By 2050, the P&PI vaccine reduced RR/MDR-TB incidence rate by 71% (UI: 69–72) and 72% (UI: 70–74), and the PSI vaccine by 31% (UI: 30–32) and 44% (UI: 42–47) in China and India, respectively. In India, we found both USD 10 P&PI and PSI vaccines cost-effective at the 1-times GDP and upper HCOC thresholds and P&PI vaccines cost-effective at the lower HCOC threshold. In China, both vaccines were cost-effective at the 1-times GDP threshold. P&PI vaccine remained cost-effective at the lower HCOC threshold with 49% probability and PSI vaccines at the upper HCOC threshold with 21% probability. The P&PI vaccine was predicted to avert 0.9 million (UI: 0.8–1.1) and 1.1 million (UI: 0.9–1.4) second-line therapy regimens in China and India between 2027 and 2050, respectively. Conclusions Novel TB vaccination is likely to substantially reduce the future burden of RR/MDR-TB, while averting the need for second-line therapy. Vaccination may be cost-effective depending on vaccine characteristics and setting.

PP581 Catastrophic Costs Of Multidrug-Resistant Tuberculosis: Estimation Based On The Cost Of Treatment In China

2020 ◽  
Vol 36 (S1) ◽  
pp. 43-43
Author(s):  
Lijun Shen ◽  
Shangshang Gu ◽  
Fan Zhang ◽  
Zhao Liu ◽  
Yuehua Liu
Keyword(s):  
Market Price ◽  
Multidrug Resistant ◽  
Policy Support ◽  
World Health ◽  
Chinese Patients ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Drug Affordability ◽  
The Cost

IntroductionChina bears a considerably high burden of multidrug-resistant tuberculosis (MDR-TB). Second-line anti-TB drugs are urgently needed yet domestic MDR-TB drugs are expensive and lack policy support. Patients’ living conditions are closely related to the drug affordability. The national TB prevention programs should play a critical role. The purpose of this study is to measure the cost of treating MDR-TB patients under different treatment schemes and price sources. The results of this study are expected to inform the relevant drug protection policies and provide inputs for further cost-effectiveness analyses.MethodsBased on the treatment plan of China's Multidrug-Resistant Pulmonary Tuberculosis Clinical Path (2012 edition) and the World Health Organization (WHO) Drug-Resistant Tuberculosis Treatment Guide (2018 edition), the treatment costs of MDR-TB were measured under different scenarios. Catastrophic health expenditure was then calculated if the treatment cost exceeds 40 percent of the household's non-subsistence income. National, rural and disposable income per capita in 2018, were used to represent Chinese patients’ affordability.ResultsUnder varied treatment schemes and market price sources in China, the total costs for MDR-TB patients range from 19,401 to 126,703 CNY [2,853 to 18,633 USD] per person. Under current prices, all treatment schemes recommended by the WHO will incur catastrophic costs for Chinese MDR-TB patients. Significant differences were found between rural and urban areas as 52.8 percent of the treatment listed in the 2012 China Guideline would lead to catastrophic cost for rural patients but not urban ones.ConclusionsOur study concludes that the domestic drugs are more expensive than the international purchase price and the treatment of MDR-TB imposes substantial economic burden on patients, especially in the rural areas. The results of the study also indicate that it is urgent for the state to emphasize government responsibility and initiate centralized procurement for price negotiations to reduce the market price of MDR-TB drugs. The urban-rural gap should also be addressed in the design of future policies to ensure the drug affordability for all patients in need.

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