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.

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.

scholarly journals Prevalence and Molecular Characterization of Second-Line Drugs Resistance among Multidrug-ResistantMycobacterium tuberculosisIsolates in Southwest of China

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Y. Hu ◽  
L. Xu ◽  
Y. L. He ◽  
Y. Pang ◽  
N. Lu ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Multidrug Resistant ◽  
Rapid Screening ◽  
Second Line ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Improper Use ◽  
Mdr Tb

This study aimed to investigate the prevalence of multidrug-resistant tuberculosis (MDR-TB) isolates resistant to the second-line antituberculosis drugs (SLDs) and its association with resistant-related gene mutations inMycobacterium tuberculosis(M.tb) isolates from Southwest of China. There were 81 isolates resistant to at least one of the SLDs among 156 MDR-TB isolates (81/156, 51.9%). The rates of general resistance to each of the drugs were as follows: OFX (66/156, 42.3%), KAN (26/156, 16.7%), CAP (13/156, 8.3%), PTO (11/156, 7.1%), PAS (22/156, 14.1%), and AMK (20/156, 12.8%). Therefore, the most predominant pattern was resistant to OFX compared with other SLDs (P<0.001). The results of sequencing showed that 80.2% OFX-resistant MDR-TB isolates containedgyrAmutation and 88.5% KAN-resistant isolates hadrrsmutations with the most frequent mutation being A1401G. These results suggest that improper use of SLDs especially OFX is a real threat to effective MDR-TB treatment not only in China but also in the whole world. Furthermore the tuberculosis control agencies should carry out SLDs susceptibility testing and rapid screening in a broader population of TB patients immediately and the SLDs should be strictly regulated by the administration in order to maintain their efficacy to treat MDR-TB.

scholarly journals Patient treatment pathways of multidrug-resistant tuberculosis cases in coastal South India: Road to a drug resistant tuberculosis center

F1000Research ◽  
2020 ◽  
Vol 8 ◽  
pp. 498
Author(s):  
Priya Rathi ◽  
Kalpita Shringarpure ◽  
Bhaskaran Unnikrishnan ◽  
Abhinav Pandey ◽  
Abhirami Nair
Keyword(s):  
Multidrug Resistant ◽  
Diagnosis And Treatment ◽  
Patient Treatment ◽  
Drug Resistant ◽  
Treatment Pathways ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
The Government

Background: Delays in initiating multidrug-resistant tuberculosis (MDR TB) treatment adds risk to individual patients and the community due to disease progression, and on-going transmission. The Government of India offers free TB diagnosis and treatment, however many presumptive MDR TB patients wander within the Indian healthcare system and delay accessing the programme. To improve access to care, it is imperative to understand the treatment pathways taken by MDR TB patients. We aimed to describe the diagnostic and treatment pathway taken by presumptive MDR TB patients registered under Programmatic Management of Drug-resistant TB Program. Methods: We conducted a cross-sectional study amongst patients registered during August 2016 – April 2017 at one District Drug Resistance Tuberculosis centre of Dakshina Kannada district in Karnataka, India. A semi-structured questionnaire was used to collect the number, type (private and public sector), and dates of healthcare facilities (HCFs) visits prior to the initiation of MDR TB treatment. Delays in pathway were measured in days and summarised as median and interquartile range (IQR), from the date of onset of illness until the initiation of MDR TB treatment. Results: We found that patients preferred private HCFs; however, due to lack of treatment and unaffordability they shifted to public HCFs. Median delay to register under the program was more in private HCFs (180 days) in comparison with public HCFs (120 days). We also found that the detection rates were much higher in public HCFs (80%). Conclusion: The present study found that there was substantial patient delay and total delay in diagnosis and treatment of MDR TB patients. Private HCF was first point of contact for most of the patients; however the diagnostic rate was high in public HCF. The government should involve private HCFs to provide standard diagnostics and treatment to the patients seeking a private facility.

scholarly journals Cumulative Fraction of Response for Once- and Twice-Daily Delamanid in Patients with Pulmonary Multidrug-Resistant Tuberculosis

2020 ◽  
Vol 65 (1) ◽  
pp. e01207-20 ◽  
Author(s):  
Suresh Mallikaarjun ◽  
Moti L. Chapagain ◽  
Tomohiro Sasaki ◽  
Norimitsu Hariguchi ◽  
Devyani Deshpande ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
System Model ◽  
Qtc Interval ◽  
Fiber System ◽  
Time Curve ◽  
Once Daily ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Concentration Time ◽  
Mdr Tb

ABSTRACTPharmacokinetic (PK) and pharmacodynamic (PD) analyses were conducted to determine the cumulative fraction of response (CFR) for 100 mg twice-daily (BID) and 200 mg once-daily (QD) delamanid in patients with multidrug-resistant tuberculosis (MDR-TB), using a pharmacodynamic target (PDT) that achieves 80% of maximum efficacy. First, in the mouse model of chronic TB, the PK/PD index for delamanid efficacy was determined to be area under the drug concentration-time curve over 24 h divided by MIC (AUC0–24/MIC), with a PDT of 252. Second, in the hollow-fiber system model of tuberculosis, plasma-equivalent PDTs were identified as an AUC0–24/MIC of 195 in log-phase bacteria and 201 in pH 5.8 cultures. Third, delamanid plasma AUC0–24/MIC and sputum bacterial decline data from two early bactericidal activity trials identified a clinical PDT of AUC0–24/MIC of 171. Finally, the CFRs for the currently approved 100-mg BID dose were determined to be above 95% in two MDR-TB clinical trials. The CFR for the 200-mg QD dose, evaluated in a trial in which delamanid was administered as 100 mg BID for 8 weeks plus 200 mg QD for 18 weeks, was 89.3% based on the mouse PDT and >90% on the other PDTs. QTcF (QTc interval corrected for heart rate by Fridericia’s formula) prolongation was approximately 50% lower for the 200 mg QD dose than the 100 mg BID dose. In conclusion, while CFRs of 100 mg BID and 200 mg QD delamanid were close to or above 90% in patients with MDR-TB, more-convenient once-daily dosing of delamanid is feasible and likely to have less effect on QTcF prolongation.

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 Hepatitis C virus infection: a challenge in the complex management of two cases of multidrug-resistant tuberculosis

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Maria Musso ◽  
Silvia Mosti ◽  
Gina Gualano ◽  
Paola Mencarini ◽  
Rocco Urso ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Side Effects ◽  
Chronic Infection ◽  
Multidrug Resistant ◽  
Hcv Infection ◽  
Second Line ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

Abstract Background Multidrug-resistant tuberculosis (MDR-TB) requires lengthy use of second-line drugs, burdened by many side effects. Hepatitis C virus (HCV) chronic infection increases risk of drug-induced liver injury (DILI) in these patients. Data on MDR-TB patients with concurrent HCV chronic infection treated at the same time with second-line antitubercular drugs and new direct-acting antivirals (DAAs) are lacking. We evaluate if treating at the same time HCV infection and pulmonary MDR-TB is feasible and effective. Cases presentation In this study, we described two cases of patients with pulmonary MDR-TB and concurrent HCV chronic infection cured with DAAs at a Tertiary Infectious Diseases Hospital in Italy. During antitubercular treatment, both patients experienced a DILI before treating HCV infection. After DAAs liver enzymes normalized and HCV RNA was undetectable. Then antitubercular regimen was started according to the institutional protocol, drawn up following WHO MDR-TB guidelines. It was completed without further liver side effects and patients were declared cured from both HCV infection and MDR-TB. Conclusions We suggest to consider treatment of chronic hepatitis C with DAAs as a useful intervention for reintroduction of second-line antitubercular agents in those patients who developed DILI, reducing the risk of treatment interruption when re-exposed to these drugs.

scholarly journals Multidrug-Resistant Tuberculosis during Pregnancy: Two Case Reports and Review of the Literature

2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
Minakshi Rohilla ◽  
Bharti Joshi ◽  
Vanita Jain ◽  
Jasvinder Kalra ◽  
G. R. V. Prasad
Keyword(s):  
Case Reports ◽  
Multidrug Resistant ◽  
Reproductive Age ◽  
Second Line ◽  
Review Of The Literature ◽  
Health Crisis ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Antituberculosis Treatment ◽  
Mdr Tb

Multidrug-resistant tuberculosis (MDR-TB) is identified from the time of introduction of antituberculosis treatment and is a known worldwide public health crisis affecting women of reproductive age group. Management issues raised by pregnant women with MDR tuberculosis are challenging due to the limited clinical experience available with the use of second line drugs. We hereby report two cases of MDR-TB during pregnancy: one patient was on second line drugs, while another one was evaluated and diagnosed to have MDR-TB in last trimester. At 6 months of follow-up both mothers and babies are doing well. The approach to such cases along with review of the literature is discussed.

scholarly journals Increased Doses Lead to Higher Drug Exposures of Levofloxacin for Treatment of Tuberculosis

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Charles A. Peloquin ◽  
Patrick P. J. Phillips ◽  
Carole D. Mitnick ◽  
Kathleen Eisenach ◽  
Ramonde F. Patientia ◽  
...  
Keyword(s):  
South Africa ◽  
Multidrug Resistant ◽  
Maximum Plasma ◽  
Second Line ◽  
Time Curve ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Concentration Time ◽  
Nominal Dose ◽  
Median Maximum

ABSTRACTPatients with multidrug-resistant tuberculosis in Peru and South Africa were randomized to a weight-banded nominal dose of 11, 14, 17, or 20 mg/kg/day levofloxacin (minimum, 750 mg) in combination with other second-line agents. A total of 101 patients were included in noncompartmental pharmacokinetic analyses. Respective median areas under the concentration-time curve from 0 to 24 h (AUC0−24) were 109.49, 97.86, 145.33, and 207.04 μg · h/ml. Median maximum plasma concentration (Cmax) were 11.90, 12.02, 14.86, and 19.17 μg/ml, respectively. Higher levofloxacin doses, up to 1,500 mg daily, resulted in higher exposures. (This study has been registered at ClinicalTrials.gov under identifier NCT01918397.)

scholarly journals Patient treatment pathways of multidrug-resistant tuberculosis cases in coastal South India: Road to a drug resistant tuberculosis center

F1000Research ◽  
2021 ◽  
Vol 8 ◽  
pp. 498
Author(s):  
Priya Rathi ◽  
Kalpita Shringarpure ◽  
Bhaskaran Unnikrishnan ◽  
Abhinav Pandey ◽  
Abhirami Nair
Keyword(s):  
Multidrug Resistant ◽  
Diagnosis And Treatment ◽  
Patient Treatment ◽  
Drug Resistant ◽  
Treatment Pathways ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
The Government

Background: Delays in initiating multidrug-resistant tuberculosis (MDR TB) treatment adds risk to individual patients and the community due to disease progression, and on-going transmission. The Government of India offers free TB diagnosis and treatment, however many presumptive MDR TB patients wander within the Indian healthcare system and delay accessing the programme. To improve access to care, it is imperative to understand the treatment pathways taken by MDR TB patients. We aimed to describe the diagnostic and treatment pathway taken by presumptive MDR TB patients registered under Programmatic Management of Drug-resistant TB Program. Methods: We conducted a cross-sectional study amongst patients registered during August 2016 – April 2017 at one District Drug Resistance Tuberculosis centre of Dakshina Kannada district in Karnataka, India. A semi-structured questionnaire was used to collect the number, type (private and public sector), and dates of healthcare facilities (HCFs) visits prior to the initiation of MDR TB treatment. Delays in pathway were measured in days and summarised as median and interquartile range (IQR), from the date of onset of illness until the initiation of MDR TB treatment. Results: We found that patients preferred private HCFs; however, due to lack of treatment and unaffordability they shifted to public HCFs. Median delay to register under the program was more in private HCFs (180 days) in comparison with public HCFs (120 days). We also found that the detection rates were much higher in public HCFs (80%). Conclusion: The present study found that there was substantial patient delay and total delay in diagnosis and treatment of MDR TB patients. Private HCF was first point of contact for most of the patients; however those visited public HCF diagnosed earlier as compared to others. The government should involve private HCFs to provide standard diagnostics and treatment to the patients seeking a private facility.

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