scholarly journals Identification of drug candidates that enhance pyrazinamide activity from a clinical drug library

2017 ◽  
Author(s):  
Hongxia Niu ◽  
Chao Ma ◽  
Peng Cui ◽  
Wanliang Shi ◽  
Shuo Zhang ◽  
...  
Keyword(s):  
Treatment Time ◽  
New Drugs ◽  
Prolonged Treatment ◽  
Drug Resistant ◽  
Drug Candidates ◽  
Resistant Tuberculosis ◽  
Multi Drug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Drug Resistant Strains ◽  
Clinical Drug

Tuberculosis (TB) remains a leading cause of morbidity and mortality globally despite the availability of the TB therapy. 1 The current TB therapy is lengthy and suboptimal, requiring a treatment time of at least 6 months for drug susceptible TB and 9-12 months (shorter Bangladesh regimen) or 18-24 months (regular regimen) for multi-drug-resistant tuberculosis (MDR-TB). 1 The lengthy therapy makes patient compliance difficult, which frequently leads to emergence of drug-resistant strains. The requirement for the prolonged treatment is thought to be due to dormant persister bacteria which are not effectively killed by the current TB drugs, except rifampin and pyrazinamide (PZA) which have higher activity against persisters. 2, 3 Therefore new therapies should address the problem of insufficient efficacy against M. tuberculosis persisters, which could cause relapse of clinical disease. 4 PZA is a critical frontline TB drug that kills persister bacteria 5 and shortens the TB treatment from 9-12 months to 6 months. 6, 7 Although several new TB drugs are showing promise in clinical studies, none can replace PZA as they all have to be used together with PZA. 7 Because of the essentiality of PZA and the high cost of developing new drugs, in this study, we explored the idea of identifying drugs that enhance the anti-persister activity of PZA as an economic alternative approach to developing new drugs for improved treatment by screening an clinical drug library against old M. tuberculosis cultures enriched with persisters.

Management of Multidrug-Resistant Tuberculosis

2018 ◽  
Vol 39 (03) ◽  
pp. 310-324 ◽  
Author(s):  
Jose Caminero ◽  
Charles Daley
Keyword(s):  
Multidrug Resistant ◽  
New Drugs ◽  
World Health ◽  
Drug Resistant ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Resistant Strains ◽  
Health Organization ◽  
Drug Resistant Strains

AbstractDrug-resistant strains of Mycobacterium tuberculosis pose a major threat to global tuberculosis control. Despite the availability of curative antituberculosis therapy for nearly half a century, inappropriate and inadequate treatment of tuberculosis, as well as unchecked transmission of M. tuberculosis, has resulted in alarming levels of drug-resistant tuberculosis. The World Health Organization (WHO) estimates that there were 600,000 cases of multidrug-resistant tuberculosis (MDR-TB)/rifampin-resistant (RR) tuberculosis in 2016, defined as strains that are resistant to at least isoniazid and rifampicin. Globally, WHO estimates that 4.1% of new tuberculosis cases and 19% of retreatment cases have MDR-TB. By the end of 2016, 123 countries had reported at least one case of extensively drug-resistant strains, which are MDR-TB strains that have acquired additional resistance to fluoroquinolones and at least one second-line injectable. It is estimated that only 22% of all MDR-TB cases are currently receiving therapy. This article reviews the management of MDR/RR-TB and updates recommendations regarding the use of shorter course regimens and new drugs.

scholarly journals Bacterial Symbionts of Soft Coral Lobophytum Sp. From Panjang Island, Jepara, Indonesia With Antimicrobial MDR TB Potency

2019 ◽  
Vol 4 (5) ◽  
pp. 194-202
Author(s):  
Yuvianti Dwi Franyoto ◽  
Ahmad Fuad Masduqi ◽  
Sakti Muchlisin ◽  
Prasetyo Abi Widyananto ◽  
Sulistiyani Sulistiyani ◽  
...  
Keyword(s):  
Bacterial Resistance ◽  
Soft Coral ◽  
New Drugs ◽  
Drug Resistant ◽  
Bacterial Symbionts ◽  
Associated Bacteria ◽  
Resistant Tuberculosis ◽  
Multi Drug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Continuous Use

Tubercolusis is a disease that attacks the lungs. The disease is caused by the bacterium mycobacterium tubercolusis. The bacteria mycobacterium tubercolusis can be killed by antibiotics. However, continuous use of antibiotics can cause bacterial resistance. So we need to find new drugs that can prevent multi-drug resistant tuberculosis. This study aims to determine the antibacterial activity of MDR TB from soft coral symbiont bacteria Lobophytum sp. There were 6 bacterial isolates obtained from soft coral Lobophytum sp. One isolate from Lobophytum-associated bacteria were successfully screened for antimycobacterial against MDR TB bacteria. PLO2 was found to inhibit the growth of MDR TB (MDR TB strain SIRE and R). Based on the results of identification with PCR, soft coral symbionts of PLO2 was closely related to Virgibacillus marismortui with homology of 99%.

scholarly journals SIDE EFFECTS ASSOCIATED WITH DRUGS USED IN TREATMENT OF MULTI DRUG RESISTANT TUBERCULOSIS AND TREATMENT RELATED FACTORS OF MULTI DRUG RESISTANT TUBERCULOSIS PATIENTS IN KATHMANDU VALLEY

2017 ◽  
Vol 14 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Chandra Prakash Bhatt ◽  
B KC
Keyword(s):  
Health Care ◽  
Side Effects ◽  
Drug Resistant ◽  
Second Line ◽  
Related Factors ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Multi Drug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Care Worker

Introduction: Treatment of multi drug resistant Mycobacterium tuberculosis (MDR-TB) with second line drugs is associated with adverse drug reactions and toxicity. Aim of this study were to determine side effects associated with drugs used in treatment of multi drug resistant tuberculosis and treatment related factors of MDR-TB patients.Methodology: A prospective study was carried out in National Tuberculosis Centre Bhaktapur Nepal. Questionnaires were used to collect data from patients.Results: Total 101 MDR TB patients were included among them majorities were male (52%) and mean age of the patients was 31.2 years. Majority of patients (87.1%) had previous history of tuberculosis treatment and 54.5% were in intensive phase of treatment. The side effect associated with drugs used in treatment of MDR-TB reported by patients were joint pain (21.2%), nausea (20.3%), hearing disturbances (11%), gastrointestinal disturbance (9.9%), depression (9.6%), itching (8.1%), hypothyroidism (6.4%), dizziness (6.4%), seizures (3.8%) and hepatitis (3.5%). Last month 25.74% patients missed one or more doses of drugs and 3.9% missed drug doses due to side effect of drugs. Majorities of the patients used vehicle to reach health centre (92.07%), time to reach the health center (59.4%) were less than 30 minutes but majorities of patients (57.4%) were not satisfied by the counseling of health care worker.Conclusion: The finding of this study shows that in MDR patients 12.8% were found new cases. Last month 3.9% patients were stopped the drugs due to side effects of drugs. Majority of patients (57.4%) were not satisfied by counseling of health care worker. Treatment of multi drug resistant tuberculosis with second line anti tubercular drugs is associated with side effects, health care worker counseling to MDR- TB patients with full attention is essential to encourage the patient’s moral and complete the treatment. Timely managing the side effects of medication is important in helping people to complete their treatment.SAARC J TUBER LUNG DIS HIV/AIDS, 2017; XIV(1), Page: 1-6

scholarly journals Intensive phase treatment outcome and associated factors among patients treated for multi drug resistant tuberculosis in Ethiopia: a retrospective cohort study

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Teklu Molie ◽  
Zelalem Teklemariam ◽  
Eveline Klinkenberg ◽  
Yadeta Dessie ◽  
Andargachew Kumsa ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Retrospective Cohort ◽  
Multinomial Logistic Regression ◽  
Drug Resistant ◽  
Contributing Factors ◽  
Drug Resistant Tuberculosis ◽  
Intensive Phase ◽  
Resistant Tuberculosis ◽  
Multi Drug Resistant Tuberculosis ◽  
Mdr Tb

Abstract Background Multi-drug resistant Tuberculosis (MDR-TB) is a strain of Mycobacterium tuberculosis that is resistant to at least Rifampicin and Isoniazid drugs. The treatment success rate for MDR-TB cases is lower than for drug susceptible TB. Globally only 55% of MDR-TB patients were successfully treated. Monitoring the early treatment outcome and better understanding of the specific reasons for early unfavorable and unknown treatment outcome is crucial for preventing the emergence of further drug-resistant tuberculosis. However, this information is scarce in Ethiopia. Therefore, this study aimed to determine the intensive phase treatment outcome and contributing factors among patients treated for MDR-TB in Ethiopia. Methods A 6 year retrospective cohort record review was conducted in fourteen TICs all over the country. The records of 751 MDR-TB patients were randomly selected using simple random sampling technique. Data were collected using a pre-tested and structured checklist. Multivariable multinomial logistic regression was undertaken to identify the contributing factors. Results At the end of the intensive phase, 17.3% of MDR-TB patients had an unfavorable treatment outcome, while 16.8% had an unknown outcome with the remaining having a favorable outcome. The median duration of the intensive phase was 9.0 months (IQR 8.04–10.54). Having an unfavorable intensive phase treatment outcome was found significantly more common among older age [ARRR = 1.047, 95% CI (1.024, 1.072)] and those with a history of hypokalemia [ARRR = 0.512, 95% CI (0.280, 0.939)]. Having an unknown intensive phase treatment outcome was found to be more common among those treated under the ambulatory care [ARRR = 3.2, 95% CI (1.6, 6.2)], rural dwellers [ARRR = 0.370, 95% CI (0.199, 0.66)], those without a treatment supporter [ARRR = 0.022, 95% CI (0.002, 0.231)], and those with resistance to a limited number of drugs. Conclusion We observed a higher rate of unfavorable and unknown treatment outcome in this study. To improve favorable treatment outcome more emphasis should be given to conducting all scheduled laboratory monitoring tests, assignment of treatment supporters for each patient and ensuring complete recording and reporting which could be enhanced by quarterly cohort review. Older aged and rural patients need special attention. Furthermore, the sample referral network should be strengthened.

scholarly journals Risk factors of Multidrug Resistant Tuberculosis in central Nepal: A pilot study

2012 ◽  
Vol 8 (4) ◽  
pp. 392-397 ◽  
Author(s):  
S B Marahatta ◽  
J Kaewkungwal ◽  
P Ramasoota ◽  
P Singhasivanon
Keyword(s):  
Risk Factors ◽  
Social Stigma ◽  
Smoking Habit ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Multi Drug Resistant Tuberculosis ◽  
National Tuberculosis ◽  
Mdr Tb ◽  
History Of

Introduction Tuberculosis is the most widespread infectious disease in Nepal and poses a serious threat to the health and development of the country. Incidences of drug resistant tuberculosis in Nepal are increasing and this tuberculosisis a major threat to successfully controlling tuberculosis . Objective The general objective of the study was to assess the risk factors of multi-drug resistant tuberculosis among the patients attending the National Tuberculosis Centre, Bhaktpur Nepal. Methods An observational study/ case-control study with a Atotal number of 55 multi-drug resistant tuberculosis cases and 55 controls. The study was conducted among the patient attending in the National Tuberculosis Centre , Bhaktpur Nepal for six months, between May–October 2010. sImulti-drug resistant tuberculosis wasThe collected data was analysed in SPSS 11.5 version. The association between categorical variables were analysed by chi-square tests, OR and their 95% CI were measured. Results The total number of patients used for the study was 110, of which among them 55 were cases and 55 were controls . Our study revealed that there were significant associations between history of prior TB MDR-TB OR =2.799 (95 % CI 1.159 to 6.667) (p=0.020); smoking habit OR =2.350 and (95%CI 1.071 to 5.159) (p=0.032); social stigma social stigma OR 2.655 (95%CI r 1.071 to 5.159) (p=0.013); knowledge on MDR-TB OR =9.643 (95% CI 3.339 to 27.846) (p < 0.001)and knowledge on DOTS Plus OR=16.714 (95% CI is ranging from 4.656 to 60.008) (p< 0.001). However, there was no association found between alcohol drinking habits and ventilation in the room. Conclusion Our study revealed that there were significant associations between history of prior tuberculosis, smoking habit social stigma social stigma, knowledge on multi-drug resistant tuberculosis and knowledge on DOTS Plus with multi-drug resistant tuberculosis However there was no association between alcohol drinking habit and ventilation in room with multi-drug resistant tuberculosis. http://dx.doi.org/10.3126/kumj.v8i4.6238 Kathmandu Univ Med J 2010;8(4):392-7

Antituberculosis activities of clofazimine and its new analogs B4154 and B4157.

1996 ◽  
Vol 40 (3) ◽  
pp. 633-636 ◽  
Author(s):  
V M Reddy ◽  
G Nadadhur ◽  
D Daneluzzi ◽  
J F O'Sullivan ◽  
P R Gangadharam
Keyword(s):  
Multidrug Resistant ◽  
New Drugs ◽  
Drug Resistant ◽  
Antituberculosis Drugs ◽  
Resistant Tuberculosis ◽  
Chemotherapeutic Activity ◽  
Resistant Strains ◽  
Intracellular Activities ◽  
Moderate Resistance ◽  
Drug Resistant Strains

In our efforts to develop new drugs for the treatment of tuberculosis, especially that caused by multidrug-resistant strains, we investigated clofazimine (CFM) and two of its analogs, B4154 and B4157, for their antituberculosis activities. Twenty M. tuberculosis strains were tested, including 16 drug-resistant strains (strains resistant to one or more antituberculosis drugs), for their susceptibilities to these three agents. All of the strains were found to be susceptible to B4154 and B4157, and one strain showed moderate resistance to CFM. The MICs of B4154, B4157, and CFM at which 90% of strains were inhibited were 0.25, 0.12, and < or = 1.0 microgram/ml, respectively. The intracellular activities of CFM and B4157 were superior to that of B4154. The chemotherapeutic activities of the three compounds were evaluated in C57BL/6 mice. At a dose of 20 mg/kg of body weight, the activity of CFM was slightly superior to that of B4157; however, both compounds prevented mortality and caused a significant reduction in the numbers of CFU in the lungs and spleens. The animals treated with B4157 showed less pigmentation than animals treated with CFM. The chemotherapeutic activity of CFM was comparable to those of rifampin and isoniazid. Complete susceptibility of multidrug-resistant strains to CFM and B4157 and the therapeutic efficacies of these compounds against mouse tuberculosis make these drugs attractive agents for the treatment of drug-resistant tuberculosis.

scholarly journals Person-centred care in practice: perspectives from a short course regimen for multi-drug resistant tuberculosis in Karakalpakstan, Uzbekistan

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Shona Horter ◽  
Beverley Stringer ◽  
Nell Gray ◽  
Nargiza Parpieva ◽  
Khasan Safaev ◽  
...  
Keyword(s):  
Decision Making ◽  
Shared Decision Making ◽  
Treatment Regimen ◽  
World Health ◽  
Drug Resistant ◽  
Shared Decision ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Multi Drug Resistant Tuberculosis ◽  
Mdr Tb

Abstract Introduction Person-centred care, an internationally recognised priority, describes the involvement of people in their care and treatment decisions, and the consideration of their needs and priorities within service delivery. Clarity is required regarding how it may be implemented in practice within different contexts. The standard multi-drug resistant tuberculosis (MDR-TB) treatment regimen is lengthy, toxic and insufficiently effective. 2019 World Health Organisation guidelines include a shorter (9–11-month) regimen and recommend that people with MDR-TB be involved in the choice of treatment option. We examine the perspectives and experiences of people with MDR-TB and health-care workers (HCW) regarding person-centred care in an MDR-TB programme in Karakalpakstan, Uzbekistan, run by Médecins Sans Frontières and the Ministry of Health. Methods A qualitative study comprising 48 interviews with 24 people with MDR-TB and 20 HCW was conducted in June–July 2019. Participants were recruited purposively to include a range of treatment-taking experiences and professional positions. Interview data were analysed thematically using coding to identify emerging patterns, concepts, and categories relating to person-centred care, with Nvivo12. Results People with MDR-TB were unfamiliar with shared decision-making and felt uncomfortable taking responsibility for their treatment choice. HCW were viewed as having greater knowledge and expertise, and patients trusted HCW to act in their best interests, deferring the choice of appropriate treatment course to them. HCW had concerns about involving people in treatment choices, preferring that doctors made decisions. People with MDR-TB wanted to be involved in discussions about their treatment, and have their preference sought, and were comfortable choosing whether treatment was ambulatory or hospital-based. Participants felt it important that people with MDR-TB had knowledge and understanding about their treatment and disease, to foster their sense of preparedness and ownership for treatment. Involving people in their care was said to motivate sustained treatment-taking, and it appeared important to have evidence of treatment need and effect. Conclusions There is a preference for doctors choosing the treatment regimen, linked to shared decision-making unfamiliarity and practitioner-patient knowledge imbalance. Involving people in their care, through discussions, information, and preference-seeking could foster ownership and self-responsibility, supporting sustained engagement with treatment.

scholarly journals RECHALLENGING TREATMENT PLAN FOR MULTIDRUG-RESISTANT TUBERCULOSIS IN DIABETIC PATIENT: A CASE REPORT

2019 ◽  
pp. 11-14 ◽  
Author(s):  
AHMED ALAA AL-TEMIMI ◽  
MUHAMMAD ZHARIF M NIZAM ◽  
YAHAYA HASSAN ◽  
NOORIZAN A AZIZ ◽  
MOHD FADLI MOHD ASMANI ◽  
...  
Keyword(s):  
Side Effect ◽  
Treatment Time ◽  
Treatment Plan ◽  
Multidrug Resistant ◽  
Prolonged Treatment ◽  
Development Of Resistance ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Hospital Acquired

Multidrug-resistant tuberculosis (MDR-TB) currently considers as the biggest issue and its subcategory, rifampicin-resistant TB (RR-TB). MDR-TB is defined as a resistant to isoniazid (H) and rifampicin (R), while the latter is resistant to rifampicin (R) only. Poorly controlled diabetes mellitus increases the risk of TB and leads to poor TB treatment outcomes as well it is consider potentially threating TB control. Difference in patients’ response and side effect developments toward anti-TB (ATB) medications requires rechallenging procedure that can be complicated at times. The management of MDR-TB can be complicated, especially, when the patient cannot tolerate the short regimen. Difference in patients’ response and side effect developments toward ATB medications requires rechallenging procedure which can have prolonged treatment time, hospital stay, and make patients exposed to hospital-acquired infection. This challenges and obstacles, however, could be prevented earlier by having strong DOTS strategy to prevent the development of resistance and reactivation of TB.

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