scholarly journals Combinations of R207910 with Drugs Used To Treat Multidrug-Resistant Tuberculosis Have the Potential To Shorten Treatment Duration

2006 ◽  
Vol 50 (11) ◽  
pp. 3543-3547 ◽  
Author(s):  
Nacer Lounis ◽  
Nicolas Veziris ◽  
Aurélie Chauffour ◽  
Chantal Truffot-Pernot ◽  
Koen Andries ◽  
...  
Keyword(s):  
Treatment Duration ◽  
Multidrug Resistant ◽  
Antiretroviral Drugs ◽  
Second Line ◽  
First Line ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
H37rv Strain ◽  
Mdr Tb ◽  
Shorten Treatment Duration

ABSTRACT The objective of the present study was to identify the optimal R207910-containing regimen to administer to patients who cannot receive rifampin (RIF) and isoniazid (INH) because of multidrug-resistant tuberculosis (MDR-TB), concomitant use of antiretroviral drugs, or toxicity. Mice were infected intravenously with 5 × 106 CFU of the H37Rv strain and treated five times per week with R207910 alone or various combinations of R207910 with the second-line drugs amikacin (AMK), pyrazinamide (PZA), moxifloxacin (MXF), and ethionamide (ETH). All R207910-containing regimens were significantly more active than the non-R207910-containing regimens after 1 month of therapy. When given for 2 months, R207910 alone was more active than the WHO standard first-line regimen RIF-INH-PZA. When R207910 was combined with second-line drugs, the combinations were more active than the currently recommended regimen of MDR-TB AMK-ETH-MXF-PZA, and culture negativity of both the lungs and spleen was reached after 2 months of treatment in almost every case.

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 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 Synthesis, Characterization and Antituberculosis Activity of Biologically Nanostructured Zinc and Titanium Metal Compounds

2020 ◽  
Vol 32 (6) ◽  
pp. 1286-1290
Author(s):  
Savita Belwal ◽  
Sujana Kariveda ◽  
Saritha Ramagiri
Keyword(s):  
Multidrug Resistant ◽  
Metal Compounds ◽  
Zinc Compounds ◽  
Macrotyloma Uniflorum ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Transmission Electron ◽  
H37rv Strain ◽  
Mdr Tb

Green chemistry was used to obtain nano-range sized titanium and zinc compounds from their macro-sizes by using an aqueous extract of horse gram (Macrotyloma uniflorum). Ultraviolet-visible (UV-vis) and Fourier-transform infrared (FTIR) spectrophotometers were employed for characterizing the nanoparticles of biosynthesized metal nanoparticles. Transmission electron microscopy (TEM) was used to analyse the reduced nanoparticles of Ti and Zn metals. Microdilution was employed to determine in vitro properties, such as effects of nanocomplex antimicrobials on Mycobacterium tuberculosis (MTB) H37RV strain. MTB strains isolated from patients with multidrug-resistant tuberculosis (MDR-TB) were resistant to first-line drugs. Novel synthesized nano-complexes exhibited potential antituberculosis activities. Titanium nanocomplexes exhibited the highest minimal inhibitory concentration (MIC) in comparison to zinc nanocomplex. In a cytotoxic study, an IC50 of 1000 μg/mL, for both Ti and Zn nanocomplexes, was reported, and thus, these complexes were non-toxic when compared to isoniazid.

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 Determination of MIC Breakpoints for Second-Line Drugs Associated with Clinical Outcomes in Multidrug-Resistant Tuberculosis Treatment in China

2016 ◽  
Vol 60 (8) ◽  
pp. 4786-4792 ◽  
Author(s):  
Xubin Zheng ◽  
Rongrong Zheng ◽  
Yi Hu ◽  
Jim Werngren ◽  
Lina Davies Forsman ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
Classification And Regression Tree ◽  
Second Line ◽  
Cart Analysis ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

ABSTRACTOur study aims to identify the clinical breakpoints (CBPs) of second-line drugs (SLDs) above which standard therapy fails in order to improve multidrug-resistant tuberculosis (MDR-TB) treatment. MICs of SLDs were determined forM. tuberculosisisolates cultured from 207 MDR-TB patients in a prospective cohort study in China between January 2010 and December 2012. Classification and regression tree (CART) analysis was used to identify the CBPs predictive of treatment outcome. Of the 207 MDR-TB isolates included in the present study, the proportion of isolates above the critical concentration recommended by WHO ranged from 5.3% in pyrazinamide to 62.8% in amikacin. By selecting pyrazinamide as the primary node (CBP, 18.75 mg/liter), 72.1% of sputum culture conversions at month four could be predicted. As for treatment outcome, pyrazinamide (CBP, 37.5 mg/liter) was selected as the primary node to predict 89% of the treatment success, followed by ofloxacin (CBP, 3 mg/liter), improving the predictive capacity of the primary node by 10.6%. Adjusted by identified confounders, the CART-derived pyrazinamide CBP remained the strongest predictor in the model of treatment outcome. Our findings indicate that the critical breakpoints of some second-line drugs and PZA need to be reconsidered in order to better indicate MDR-TB treatment outcome.

scholarly journals Outcomes with a shorter multidrug-resistant tuberculosis regimen from Karakalpakstan, Uzbekistan

2020 ◽  
pp. 00537-2020
Author(s):  
Philipp du Cros ◽  
Khamraev Atadjan ◽  
Tigay Zinaida ◽  
Tleubergen Abdrasuliev ◽  
Jane Greig ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Fluoroquinolone Resistance ◽  
Second Line ◽  
Serious Adverse Events ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

BackgroundIn 2016, WHO guidelines conditionally recommended standardised shorter 9–12 month regimens for multidrug-resistant tuberculosis (MDR-TB) treatment. We conducted a prospective study of a shorter standardised MDR-TB regimen in Karakalpakstan, Uzbekistan.MethodsConsecutive adults and children with confirmed rifampicin-resistant pulmonary TB were enrolled between 1st September 2013 and 31st March 2015; exclusions included prior treatment with second-line anti-TB drugs, and documented resistance to ofloxacin or to two second-line injectable agents. The primary outcome was recurrence-free cure at 1 year following treatment completion.ResultsOf 146 enrolled, 128 patients were included: 67 female (52.3%), median age 30.1 (IQR 23.8–44.4) years. At the end of treatment, 71.9% (92/128) patients achieved treatment success, with 68% (87/128) achieving recurrence-free cure at 1 year following completion. Unsuccessful outcomes during treatment included 22 (17.2%) treatment failure with fluoroquinolone resistance amplification in 8 patients (8/22, 36.4%); 12 (9.4%) loss to follow-up; 2 (1.5%) deaths. Recurrence occurred in one patient. 14 patients (10.9%) experienced serious adverse events. Baseline resistance to both pyrazinamide and ethambutol (aOR 6.13, 95% CI 2.01;18.63) and adherence<95% (aOR 5.33, 95% CI 1.73;16.36) were associated with unsuccessful outcome in multivariable logistic regression.ConclusionsOverall success with a standardised shorter MDR-TB regimen was moderate with considerable treatment failure and amplification of fluoroquinolone resistance. When introducing standardised shorter regimens, baseline drug susceptibility testing and minimising missed doses are critical. High rates globally of pyrazinamide, ethambutol and ethionamide resistance raise questions of continued inclusion of these drugs in shorter regimens in the absence of DST-confirmed susceptibility.

scholarly journals Multidrug Resistant Tuberculosis in Children in Port Harcourt – A Worrisome Trend

2019 ◽  
pp. 1-8
Author(s):  
Lucy Eberechukwu Yaguo Ide ◽  
Nsirimobu Ichendu Paul ◽  
Rosemary Ogochukwu Ugwu
Keyword(s):  
Multidrug Resistant ◽  
Drug Resistant ◽  
Second Line ◽  
Female Ratio ◽  
Intensive Phase ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Port Harcourt ◽  
Mdr Tb ◽  
Paediatric Tuberculosis

Background: Drug-resistant tuberculosis and multidrug-resistant tuberculosis (MDR-TB) in particular represent a major threat to the fight against tuberculosis globally. MDR-TB presents with similar features and is transmitted in the same way as drug sensitive TB but its progression is rapid and its treatment, associated drug toxicity and monitoring constitute a heavy burden to the patients and the health system. MDR-TB affect people of all age groups but very little is known about the magnitude of this problem in children. Aims/Objectives: To determine the prevalence of multidrug resistant tuberculosis among children in Port Harcourt. Materials and Methods: Information on Paediatric tuberculosis was retrieved from the patients’ case notes, TB registers at the directly observed treatment short course (DOTs) clinic and the Multidrug resistant tuberculosis (MDR-TB) treatment center of the University of Port Harcourt Teaching Hospital from January 2018 to June 2019. Obtained data was analysed and presented in prose and tables.  Results: There was a total of 1,860 patients records of which 37 were Paediatrics cases giving a prevalence of Paediatric tuberculosis cases of 2.0% Out of these 37cases, four were multidrug resistant tuberculosis cases giving a prevalence of MDR-TB cases of 10.8%. There were three males and one female giving a male female ratio of 3: 1. and their ages ranged from 3months to 24months. All belonged to social class 5.  Common presentation was chronic cough, prolonged fever, weight loss and lymph node swellings. Three (75%) had no prior treatment for tuberculosis while one (25%) completed 6months of anti TB drugs. All had BCG immunization within one week of delivery. One (25%) child had extra-pulmonary TB while 3(75%) children had pulmonary tuberculosis. Xpert MTB/RIF assay for all (100%) showed MTB detected, RIF resistant detected. Three (75%) of the mothers had MDRTB and the medications for their children was based on the drug sensitivity testing (DST) of their mothers. One (25%) of the children and his mother were HIV positive and the mother had died while still on the intensive phase of second line antiTB drugs. Three (75%) had completed the intensive phase of the conventional therapy with second line antiTB drugs and are closely followed up weekly on the continuation phase while one child is still on admission. Conclusions: The prevalence of MDR-TB in children in PH is high. All childhood TB (whether drug susceptible or drug resistant) is usually traced to an adult, thus effectively diagnosing and     treating all adults as well as a high index of suspicion in presumptive cases is required to curb MDR-TB. Recommendations: We recommend strict use of the DOTs strategy in TB management to ensure drug adherence. Also, proper contact tracing, investigation and treatment of children of infected parents to reduce cases of MDR-TB is advocated. 

Sign in / Sign up

Export Citation Format

Share Document