scholarly journals In-vitro Anti-Tuberculosis, Anti-Efflux Pumps and Anti-Biofilm Effects of Crinum Asiaticum Bulbs

2021 ◽  
Vol 14 (4) ◽  
pp. 1905-1915
Author(s):  
Michael Ofori ◽  
Cynthia Amaning Danquah ◽  
Selase Ativui ◽  
Peace Doe ◽  
Williams Adu Asamoah
Keyword(s):  
Biofilm Formation ◽  
Efflux Pumps ◽  
Chloroform Extract ◽  
World Health ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Tract Infections ◽  
Crinum Asiaticum

Drug resistant tuberculosis remains one of the major challenges associated with treatment and management of tuberculosis (TB) in the public health system and in clinical settings. In 2020, the World Health Organization (WHO) estimated that about 186,772 people died from drug-resistant tuberculosis out of the 500000 reported cases and this is alarming. There is a pressing need from every angle in drug discovery to develop novel compounds that could possess diverse mechanisms of action to tackle drug-resistant tuberculosis. The Crinum asiaticum bulbs extract are used ethno medicinally to treat upper respiratory tract infections and as well as wound healing agent. The aim of this work is to investigate the in-vitro anti-tuberculosis effect of Crinum asiaticum bulbs extracts and to assess the inhibitory properties against bacteria efflux pumps expression and biofilm formation. The results obtained showed that the Crinum asiaticum bulbs extracts (CAE) were effective in inhibiting Mycobacterium smegmatis (NCTC 8159) and Mycobacterium aurum (NCTC 10437) with minimum inhibitory concentration (MIC) of 125 μg/ml and 250 μg/ml against M. smegmatis and M. aurum respectively. The CAE markedly inhibited the efflux pumps of both M. smegmatis and M. aurum from expressing with the chloroform extract producing the greatest inhibition. The CAE (ethanol, methanol, chloroform and hexane) significantly (***ρ˂0.005) inhibited M. smegmatis’ and M. aurum’s biofilm formation in-vitro. Among the various extracts of Crinum asiaticum, the chloroform extract exhibited the greatest inhibition against M. smegmatis and M. aurum biofilm formation with significance levels of ***ρ˂0.005 and ***ρ˂0.005. In conclusion the CAE has anti-tuberculosis effect and could tackle drug resistant TB as exhibited through the anti-efflux and anti-biofilm forming properties of the extract against the selected Mycobacterium species.

Exploring patient-provider factors for risk of developing Multi-drug Resistance Tuberculosis in Southern Ethiopia: Qualitative Operation Research (Preprint)

2019 ◽  
Author(s):  
Yitagesu Habtu ◽  
Tesema Bereku ◽  
Girma Alemu ◽  
Ermias Abera
Keyword(s):  
Phenomenological Study ◽  
Treatment Success ◽  
World Health ◽  
Multi Drug Resistance ◽  
Southern Ethiopia ◽  
Drug Resistant ◽  
Related Factors ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Multi Drug Resistant Tuberculosis

BACKGROUND Ethiopia is one of among thirty high burden countries of multi-drug resistant tuberculosis (MDR-TB) in the regions of world health organization. Contextual evidence on the emergence of the disease is limited at a program level. OBJECTIVE The aim of the study is to explore patient-provider factors that may facilitate the emergence of multi-drug resistant tuberculosis. METHODS We used a phenomenological study design of qualitative approach from June to July, 2015. We conducted ten in-depth interviews and 4 focus group discussions with purposely selected patients and providers. We designed and used an interview guide to collect data. Verbatim transcribes were exported to open code 3.4 for emerging thematic analysis. Domain summaries were used to support core interpretation. RESULTS The study explored patient-provider factors facilitating the emergence of multi-drug resistant tuberculosis. These factors as underlying, health system and patient-related factors. Especially, the a shows conflicting finding between having a history of discontinuing drug-susceptible tuberculosis and emergence of multi-drug resistant tuberculosis. CONCLUSIONS The patient-provider factors may result in poor early case identification, adherence to and treatment success in drug sensitive or multi-drug resistant tuberculosis. Our study implies the need for awareness creation about multi-drug resistant tuberculosis for patients and further familiarization for providers. This study also shows that patients developed multi-drug resistant tuberculosis though they had never discontinued their drug-susceptible tuberculosis treatment. Therefore, further studies may require for this discording finding.

All-oral longer regimens are effective for the management of multidrug resistant tuberculosis in high burden settings

2021 ◽  
pp. 2004345
Author(s):  
Palwasha Y. Khan ◽  
Molly F. Franke ◽  
Catherine Hewison ◽  
Kwonjune J. Seung ◽  
Helena Huerga ◽  
...  
Keyword(s):  
Relative Risk ◽  
World Health ◽  
Potential Contribution ◽  
Adjusted Relative Risk ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Oral Regimen ◽  
Significant Difference ◽  
Culture Conversion

BackgroundRecent World Health Organisation guidance on drug-resistant tuberculosis treatment de-prioritised injectable agents, in use for decades, and endorsed all-oral longer regimens. However, questions remain about the role of the injectable agent, particularly in the context of regimens using new and repurposed drugs. We compared the effectiveness of an injectable-containing regimen to that of an all-oral regimen among patients with drug-resistant tuberculosis who received bedaquiline- and/or delamanid as part of their multidrug regimen.MethodsPatients with a positive baseline culture were included. Six-month culture conversion was defined as two consecutive negative cultures collected >15 days apart. We derived predicted probabilities of culture conversion and relative risk using marginal standardisation methods.ResultsCulture conversion was observed in 83.8% (526/628) of patients receiving an all-oral regimen and 85.5% (425/497) of those receiving an injectable-containing regimen. The adjusted relative risk comparing injectable-containing regimens to all-oral regimens was 0.96 (95%CI: 0.88–1.04). We found very weak evidence of effect modification by HIV status: among patients living with HIV, there was a small increase in the frequency of conversion among those receiving an injectable-containing regimen, relative to an all-oral regimen, which was not apparent in HIV-negative patients.ConclusionsAmong individuals receiving bedaquiline and/or delamanid as part of a multidrug regimen for drug-resistant tuberculosis, there was no significant difference between those who received an injectable and those who did not regarding culture conversion within 6 months. The potential contribution of injectable agents in the treatment of drug-resistant tuberculosis among those who were HIV positive requires further study.

scholarly journals Treatment of Drug-Resistant Tuberculosis: Current Status

2020 ◽  
Author(s):  
Rajendra Prasad ◽  
Harsh Saxena ◽  
Nikhil Gupta ◽  
Mohammad Tanzeem ◽  
Ronal Naorem
Keyword(s):  
Total Duration ◽  
World Health ◽  
Current Status ◽  
Current Evidence ◽  
Drug Resistant ◽  
Second Line ◽  
Drug Resistant Tuberculosis ◽  
Intensive Phase ◽  
Resistant Tuberculosis ◽  
Mdr Tb

AbstractDrug-resistant tuberculosis (DR-TB) has been an area of growing concern and posing threat to human health worldwide. The treatment has been defined for all types of DR-TB with or without newer anti-TB drugs. multi-DR-TB (MDR-TB) patients have now choice of two types of regimen, shorter and longer regimens. Shorter regimen for treatment of subset of MDR-TB patients who have not been previously treated with second line drugs and in whom resistance to fluoroquinolones and second-line injectable agents has been excluded is given for 9 to 11 months. A longer regimen of at least five effective anti-TB drugs (ATDs) during the intensive phase is recommended, including pyrazinamide and four core second-line ATDs. Intensive phase, including injectables, should be given for at least 8 months. The total duration of treatment is at least 20 months, which can be prolonged up to 24 months depending on the response of the patient. World Health Organization (WHO) has recently revised the grouping of ATD for use in DR-TB patients in 2018 into three groups based on individual patient data meta-analysis depending on their individual efficacy, risk of relapse, treatment failure, and death. Recently, an all oral longer regimen comprising bedaquiline, pretomanid, and linezolid (BPal regime) for 6 to 9 months for extensive-DR-TB (XDR-TB) patients and those MDR-TB patients who cannot tolerate or do not respond to conventional MDR-TB regimen. These new developments will be a step forward toward establishing universal regimen to treat all types of DR-TB. This article has summarized the current evidence from literature search to date, including prevalence of DR-TB, types of regimen used and the advancement in the regimens for effective treatment of DR-TB patients.

scholarly journals Linezolid Pharmacokinetics in South African Patients with Drug-Resistant Tuberculosis and a High Prevalence of HIV Coinfection

2019 ◽  
Vol 63 (3) ◽  
Author(s):  
Sean Wasserman ◽  
Paolo Denti ◽  
James C. M. Brust ◽  
Mahmoud Abdelwahab ◽  
Siphokazi Hlungulu ◽  
...  
Keyword(s):  
South African ◽  
Critical Concentration ◽  
Therapeutic Index ◽  
World Health ◽  
Drug Resistant ◽  
Target Attainment ◽  
Time Curve ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
African Patients

ABSTRACT The World Health Organization (WHO) recently recommended that linezolid be prioritized in treatment regimens for drug-resistant tuberculosis (TB), but there are limited data on its pharmacokinetics (PK) in patients with this disease. We conducted an observational study to explore covariate effects on linezolid PK and to estimate the probability of PK/pharmacodynamic target attainment in South African patients with drug-resistant TB. Consecutive adults on linezolid-based regimens were recruited in Cape Town and underwent intensive PK sampling at steady state. Noncompartmental analysis was performed. Thirty participants were included: 15 HIV positive, 26 on the initial dose of 600 mg daily, and 4 participants on 300 mg daily after dose reduction for linezolid-related toxicity. There was a negative correlation between body weight and exposure, with 17.4% (95% confidence interval [CI], 0.1 to 31.7) decrease in area under the concentration-time curve from 0 to 24 h (AUC0–24) per 10-kg weight increment after adjustment for other covariates. Age was an independent predictor of trough concentration, with an estimated 43.4% (95% CI, 5.9 to 94.2) increase per 10-year increment in age. The standard 600-mg dose achieved the efficacy target of free AUC/MIC of >119 at wild-type MIC values (≤0.5 mg/liter), but the probability of target attainment dropped to 61.5% (95% CI, 40.6 to 79.8) at the critical concentration of 1 mg/liter. When dosed at 600 mg daily, trough concentrations were above the toxicity threshold of 2 mg/liter in 57.7% (95% CI, 36.9 to 76.6). This confirms the narrow therapeutic index of linezolid, and alternative dosing strategies should be explored.

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 Directrices unificadas de la OMS sobre el tratamiento de la tuberculosis farmacorresistente

2020 ◽  
Keyword(s):  
World Health Organization ◽  
Tuberculosis Treatment ◽  
World Health ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Health Organization

Estas directrices unificadas se han actualizado con arreglo a los procesos del grupo de elaboración de las directrices que se llevaron a cabo entre el 2011 y el 2018 de conformidad con los requisitos de la OMS. Este documento sustituye a otras recomendaciones de la OMS relativas al tratamiento de la tuberculosis (TB) multirresistente y resistente a la rifampicina (TB-MDR/RR) publicadas desde el 201. En este documento se incluyen las preguntas sobre población, intervención, comparador y resultado (PICO, por su sigla en inglés) subyacentes a las recomendaciones y la posología revisada de los medicamentos utilizados en los esquemas de segunda línea, así como las referencias clave. En línea se puede encontrar más información sobre los procesos del grupo de elaboración de las directrices y los participantes en dicho grupo, los principales métodos utilizados para desarrollar las recomendaciones, los resúmenes de la evidencia de la clasificación de la valoración, elaboración y evaluación de las recomendaciones (GRADE por su sigla en inglés) resultante y los marcos de decisión para cada recomendación, así como datos inéditos, planes de análisis de datos e informes de revisiones sistemáticas. Las recomendaciones y demás información práctica para apoyar su implementación se reproducirán en una próxima actualización del manual de la OMS sobre el manejo programático de la TB. Versión oficial en español de la obra original en inglés: WHO consolidated guidelines on drug-resistant tuberculosis treatment. © World Health Organization 2019. ISBN: 978-92-4-155052-9.

scholarly journals Pharmacokinetics and target attainment of SQ109 in plasma and human-like tuberculosis lesions in rabbits

2021 ◽  
Author(s):  
Oluwaseun Egbelowo ◽  
Jansy P. Sarathy ◽  
Kamunkhwala Gausi ◽  
Matthew D. Zimmerman ◽  
Han Wang ◽  
...  
Keyword(s):  
Rabbit Model ◽  
Multidrug Resistant ◽  
Clinical Development ◽  
Drug Candidate ◽  
Parameter Estimates ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Bacterial Populations ◽  
Resistant Tuberculosis

SQ109 is a novel well-tolerated drug candidate in clinical development for the treatment of drug resistant tuberculosis (TB). It is the only inhibitor of the MmpL3 mycolic acid transporter in clinical development. No SQ109 resistant mutant has been directly isolated thus far, in vitro, in mice or in patients, tentatively attributed to its multiple targets. It is considered as a potential replacement for poorly tolerated components of multidrug-resistant TB regimens. To prioritize SQ109-containing combinations with best potential for cure and treatment shortening, one must understand its contribution against different bacterial populations in pulmonary lesions. Here we have characterized the pharmacokinetics of SQ109 in the rabbit model of active TB and its penetration at the sites of disease: lung tissue, cellular and necrotic lesions, and caseum. A two-compartment model with first-order absorption and elimination described the plasma pharmacokinetics. At the human-equivalent dose, parameter estimates fell within the ranges published for preclinical species. Tissue concentrations were modelled using an "effect" compartment, showing high accumulation in lung and cellular lesion areas with penetration coefficients in excess of 1,000, and lower passive diffusion in caseum after 7 daily doses. These results, together with the hydrophobic nature and high non-specific caseum binding of SQ109, suggest that multi-week dosing would be required to reach steady state in caseum and poorly vascularized compartments, similar to bedaquiline. Linking lesion pharmacokinetics to SQ109 potency in assays against replicating, non-replicating, and intracellular M. tuberculosis showed SQ109 concentrations markedly above pharmacokinetic-pharmacodynamic targets in lung and cellular lesions throughout the dosing interval. IMPORTANCE Drug-resistant tuberculosis (TB) accounts for over 20% of all fatalities due to drug-resistant pathogens. With recently approved drugs and a promising drug candidate pipeline, the challenge faced by clinical developers is prioritization of drug combinations with the best potential to improve cure rates and shorten treatment duration. To this end, one must understand the contribution of each partner drug against different bacterial populations in pulmonary TB lesions. SQ109 is a safe drug candidate in clinical development for the treatment of multidrug resistant TB. It is active against replicating and non-replicating Mycobacterium tuberculosis persisters in vitro, in mouse models and in patients. SQ109 exhibits extremely low frequency of resistance, unprecedented among all TB drugs so far. Here we characterize the pharmacokinetics and activity of SQ109 at the site of TB disease to inform the selection of drug regimens that account for its lesion-centric pharmacokinetic-pharmacodynamic parameters and best leverage its contribution to efficient disease cure.

scholarly journals The challenge of managing extensively drug-resistant tuberculosis at a referral hospital in the state of São Paulo, Brazil: a report of three cases

2015 ◽  
Vol 41 (6) ◽  
pp. 554-559 ◽  
Author(s):  
Marcos Abdo Arbex ◽  
Hélio Ribeiro de Siqueira ◽  
Lia D'Ambrosio ◽  
Giovanni Battista Migliori
Keyword(s):  
Sao Paulo ◽  
The State ◽  
Referral Hospital ◽  
World Health ◽  
Drug Resistant ◽  
São Paulo ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Laboratory Test Results

ABSTRACT Here, we report the cases of three patients diagnosed with extensively drug-resistant tuberculosis and admitted to a referral hospital in the state of São Paulo, Brazil, showing the clinical and radiological evolution, as well as laboratory test results, over a one-year period. Treatment was based on the World Health Organization guidelines, with the inclusion of a new proposal for the use of a combination of antituberculosis drugs (imipenem and linezolid). In the cases studied, we show the challenge of creating an acceptable, effective treatment regimen including drugs that are more toxic, are more expensive, and are administered for longer periods. We also show that treatment costs are significantly higher for such patients, which could have an impact on health care systems, even after hospital discharge. We highlight the fact that in extreme cases, such as those reported here, hospitalization at a referral center seems to be the most effective strategy for providing appropriate treatment and increasing the chance of cure. In conclusion, health professionals and governments must make every effort to prevent cases of multidrug-resistant and extensively drug-resistant tuberculosis.

scholarly journals Beta-lactam antibiotics as reserve medications for the treatment of drug-resistant tuberculosis

2021 ◽  
Vol 66 (5-6) ◽  
pp. 78-85
Author(s):  
G. N. Mozhokina ◽  
A. G. Samoilova ◽  
I. A. Vasilyeva
Keyword(s):  
Drug Resistance ◽  
Review Article ◽  
Drug Resistant ◽  
Beta Lactam ◽  
Drug Resistant Tuberculosis ◽  
Beta Lactam Antibiotics ◽  
Resistant Tuberculosis ◽  
Extensive Drug Resistance ◽  
Tuberculosis Activity

The review article presents an analysis of literature data on the necessity to expand the range of medications possessing anti-tuberculosis activity for the treatment of the most severe forms of drug-resistant tuberculosis through the use of beta-lactam antibiotics in chemotherapy regimens. The mechanism of action of beta- lactam antibiotics on mycobacterium tuberculosis is shown, and the results of in vitro studies to assess their anti-tuberculosis activity are presented. Clinical studies on the use of carbapenems prove the feasibility of their use for the treatment of patients with tuberculosis with multiple and extensive drug resistance of the pathogen.

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