scholarly journals Synthesis and Characterization of a Biomimetic Formulation of Clofazimine Hydrochloride Microcrystals for Parenteral Administration

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 238 ◽  
Author(s):  
Mikhail Murashov ◽  
Jennifer Diaz-Espinosa ◽  
Vernon LaLone ◽  
Joel Tan ◽  
Raluca Laza ◽  
...  
Keyword(s):  
Side Effect ◽  
Skin Pigmentation ◽  
Reticuloendothelial System ◽  
Multidrug Resistant ◽  
World Health ◽  
Line Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Skin Accumulation ◽  
Health Organization

Clofazimine (CFZ) is a broad spectrum antimycobacterial agent recommended by the World Health Organization as a first line treatment for leprosy and second line treatment for multidrug resistant tuberculosis. Oral administration of CFZ leads to a red skin pigmentation side effect. Since CFZ is a weakly basic, red phenazine dye, the skin pigmentation side effect results from lipophilic partitioning of the circulating, free base (neutral) form of CFZ into the skin. Here, we developed a stable and biocompatible formulation of CFZ-HCl microcrystals that mimics the predominant form of the drug that bioaccumulates in macrophages, following long term oral CFZ administration. In mice, intravenous injection of these biomimetic CFZ-HCl microcrystals led to visible drug accumulation in macrophages of the reticuloendothelial system with minimal skin accumulation or pigmentation. In fact, no skin pigmentation was observed when the total amount of CFZ-HCl administered was equivalent to the total oral dose leading to maximal skin pigmentation. Thus, parenteral (injected or inhaled) biomimetic formulations of CFZ-HCl could be instrumental to avoid the pigmentation side effect of oral CFZ therapy.

World Health Organization recommendations for multidrug-resistant tuberculosis: should different standards be applied?

2017 ◽  
Vol 21 (12) ◽  
pp. 1211-1213 ◽  
Author(s):  
V. Cox ◽  
J. Furin
Keyword(s):  
World Health Organization ◽  
Safety Data ◽  
Evaluation Process ◽  
Multidrug Resistant ◽  
World Health ◽  
Efficacy And Safety ◽  
Assessment Development ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Health Organization

The World Health Organization uses a Grading of Recommendations Assessment, Development, and Evaluation process to make recommendations for treating multidrug-resistant tuberculosis. Even with this standardized approach, there have been discrepancies between recommendations for newer drugs such as bedaquiline and delamanid and the shorter regimen. This may be because newer drugs are novel chemical entities and may merit closer scrutiny. Here, we explore the problematic nature of this supposition, arguing that although the newer drugs have been used in fewer individuals, they may have more robust efficacy and safety data than many of the second-line drugs used in the shorter regimen.

Multidisciplinary advisory teams to manage multidrug-resistant tuberculosis: the example of the French Consilium

2019 ◽  
Vol 23 (10) ◽  
pp. 1050-1054
Author(s):  
L. Guglielmetti ◽  
J. Jaffré ◽  
C. Bernard ◽  
F. Brossier ◽  
N. El Helali ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
New Drugs ◽  
World Health ◽  
Advisory Committees ◽  
Treatment Regimens ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Health Organization

SETTING: The World Health Organization (WHO) recommends that multidrug-resistant tuberculosis (MDR-TB) treatment should be managed in collaboration with multidisciplinary advisory committees (consilia). A formal national Consilium has been established in France since 2005 to provide a centralised advisory service for clinicians managing MDR-TB and extensively drug-resistant (XDR-TB) cases.OBJECTIVE: Review the activity of the French TB Consilium since its establishment.DESIGN: Retrospective description and analysis of the activity of the French TB Consilium.RESULTS: Between 2005 and 2016, 786 TB cases or contacts of TB cases were presented at the French TB Consilium, including respectively 42% and 79% of all the MDR-TB and XDR-TB cases notified in France during this period. Treatment regimens including bedaquiline and/or delamanid were recommended for 42% of the cases presented at the French TB Consilium since 2009. Patients were more likely to be presented at the French TB Consilium if they were born in the WHO Europe Region, had XDR-TB, were diagnosed in the Paris region, or had resistance to additional drugs than those defining XDR-TB.CONCLUSION: The French TB Consilium helped supervise appropriate management of MDR/XDR-TB cases and facilitated implementation of new drugs for MDR/XDR-TB treatment.

scholarly journals Multidrug-resistant tuberculosis infection and disease in children: a review of new and repurposed drugs

2019 ◽  
Vol 6 ◽  
pp. 204993611986473 ◽  
Author(s):  
Julie Huynh ◽  
Ben J. Marais
Keyword(s):  
Clinical Care ◽  
Multidrug Resistant ◽  
World Health ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Resource Limited ◽  
Prevention And Treatment ◽  
Mdr Tb ◽  
Repurposed Drugs ◽  
Health Organization

The World Health Organization estimates that 10 million new cases of tuberculosis (TB) occurred worldwide in 2017, of which 600,000 were rifampicin or multidrug-resistant (RR/MDR) TB. Modelling estimates suggest that 32,000 new cases of MDR-TB occur in children annually, but only a fraction of these are correctly diagnosed and treated. Accurately diagnosing TB in children, who usually have paucibacillary disease, and implementing effective TB prevention and treatment programmes in resource-limited settings remain major challenges. In light of the underappreciated RR/MDR-TB burden in children, and the lack of paediatric data on newer drugs for TB prevention and treatment, we present an overview of new and repurposed TB drugs, describing the available evidence for safety and efficacy in children to assist clinical care and decision-making.

scholarly journals Short-course treatment for multidrug-resistant tuberculosis: the STREAM trials

2016 ◽  
Vol 25 (139) ◽  
pp. 29-35 ◽  
Author(s):  
Riya Moodley ◽  
Thomas R. Godec
Keyword(s):  
Treatment Options ◽  
Standard Of Care ◽  
Multidrug Resistant ◽  
World Health ◽  
Efficacy And Safety ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Health Organization ◽  
Stage 1

Multidrug-resistant (MDR) tuberculosis (TB) is a threat to global TB control, as suboptimal and poorly tolerated treatment options have resulted in largely unfavourable outcomes for these patients. The last of six cohort studies conducted in Bangladesh which assessed a new shorter regimen using currently available TB drugs showed promising results and offered the possibility of a more acceptable and more effective regimen than the one recommended by the World Health Organization (WHO). The aims of stage 1 of the STREAM (Evaluation of a Standardised Treatment Regimen of Anti-tuberculosis Drugs for Patients with Multidrug-resistant Tuberculosis) trial are to evaluate the efficacy and safety of this regimen, compared to the current WHO-recommended standard of care. Stage 2 evaluates two new bedaquiline-containing regimens: one an all-oral regimen and the second a further shortened and simplified version of the stage 1 study regimen, comparing the efficacy and safety of each to that of the stage 1 study regimen and also to the WHO-recommended standard of care. Success of the stage 1 study regimen would in all probability provide a new standard of care for MDR-TB patients, while positive results from the bedaquiline-containing regimens in stage 2 may allow for even greater progress in the management of this difficult population.

scholarly journals Effectiveness and Safety of a Shorter Treatment Regimen in a Setting with a High Burden of Multidrug-Resistant Tuberculosis

2021 ◽  
Vol 18 (8) ◽  
pp. 4121
Author(s):  
Aleksandr Trubnikov ◽  
Arax Hovhannesyan ◽  
Kristina Akopyan ◽  
Ana Ciobanu ◽  
Dilbar Sadirova ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
World Health ◽  
Hiv Status ◽  
Treatment Regimens ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Grade 3 ◽  
Health Organization ◽  
Lost To Follow Up

Treatment of drug-resistant tuberculosis is lengthy, insufficiently effective, and toxic. Since 2016, the World Health Organization has recommended shorter treatment regimens (STR). We assessed effectiveness and predictors of drug adverse events (DAE) among patients treated with STR. There were 95 consecutive rifampicin-resistant patients enrolled in STR in Tashkent between June 2018 and September 2019. Of these, 66.3% were successfully treated, 17.9% suffered failed treatment, 7.4% died, 5.3% were lost to follow-up and 3.2% were not evaluated. No recurrence was identified in 54 patients after 12 months of successful treatment completion. There were 47 reported DAE: the incidence rate was 6.15 DAE per 100 person-months-of-treatment. Any DAE was reported in 38 (40%) patients and grade 3/4 DAE were recorded in 21 (22.1%) patients. Median time to DAE was 101 (interquartile range 64–139) days. The most frequently encountered DAE were gastro-intestinal disorders, followed by hepatotoxicity and ototoxicity. The most commonly offending drug inducing DAE was protionamide. The dose was temporarily interrupted in 55.3% of DAE, reduced in 8.5% of DAE and permanently withdrawn in another 8.5% of DAE. HIV status was the only predictor associated with increased hazard of DAE. In Uzbekistan STR showed moderate effectiveness and safety, although treatment failure was high.

scholarly journals Linezolid-induced black hairy tongue in a patient with multidrug-resistant tuberculosis: A case report

2021 ◽  
Vol 104 (3) ◽  
pp. 003685042110429
Author(s):  
Jaemin Lee ◽  
Hyun Sung Chung ◽  
Jiyeon Roh ◽  
Yeseul Oh ◽  
Jeongha Mok
Keyword(s):  
Multidrug Resistant ◽  
Bone Marrow Suppression ◽  
World Health ◽  
Limited Information ◽  
The Core ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Health Organization ◽  
Black Hairy Tongue

The revised World Health Organization guidelines on multidrug-resistant tuberculosis include linezolid in the core drugs group. Consequently, the use of linezolid for patients with multidrug-resistant tuberculosis is increasing. Common adverse events of long-term linezolid use include bone marrow suppression and neuropathies. However, there is limited information on a rare adverse event, black hairy tongue. Here, we report a case of linezolid-induced black hairy tongue in a patient with multidrug-resistant tuberculosis. The etiology, pathogenesis, diagnosis, and treatment of black hairy tongue are also discussed.

scholarly journals Prevalence of Multidrug Resistance Mycobacterium Tuberculosis (MDR-TB) Using GeneXpert Assay in Northern Sudan, How Serious is the Situation?

2021 ◽  
Author(s):  
Sufian Khalid Noor ◽  
Mohamed Osman Elamin ◽  
Ziryab Imad Mahmoud ◽  
Mohammed Salah ◽  
Taqwa Anwar ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Multidrug Resistant ◽  
World Health ◽  
River Nile ◽  
Cross Sectional ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
History Of ◽  
Health Organization

Background: World Health Organization (WHO) estimates that there were 558000 new cases with resistance to Rifampicin, of which 82% had multidrug-resistant tuberculosis (MDR-TB). Objectives: We aimed to identify the prevalence of MDR-TB in River Nile state, Sudan, and the risk factors contributing to its occurrence. Methods: This was a descriptive cross-sectional hospital-based study involved 200 specimens taken from patients suspected of having MDR-TB tested using an automated GeneXpert assay. Results: Results of GeneXpert assay showed that the presence of Mycobacterium tuberculosis in 81 (40.5%), and out of 81 positive test results there were 13 (16%) had MDR-TB. Additionally, 7 cases of MDR-TB were previously treated which represented about (53%) of MDR patients, the remaining 6 MDR-TB patients were new cases and represented (47%) of MDR-TB patients. Moreover, there were 4 MDR-TB patients who had a history of contact with MDR-TB patients. Conclusion: Prevalence of MDR-TB in River Nile State, Sudan was 16%, which is greater than WHO estimation for Sudan (10.1%). The results revealed that the main risk factor to develop MDR-TB was a history of contact with MDR-TB, so adherence to treatment and social awareness about the spread of MDR-TB are crucial preventive measures.

Treatment Outcomes of Patients Switching From an Injectable Drug to Bedaquiline During Short Standardized Treatment for Multidrug-resistant Tuberculosis in Mozambique

2019 ◽  
Vol 69 (10) ◽  
pp. 1809-1811 ◽  
Author(s):  
Mathieu Bastard ◽  
Lucas Molfino ◽  
Cláudia Mutaquiha ◽  
Miriam Arago Galindo ◽  
Pereira Zindoga ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
World Health ◽  
Injectable Drug ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
The World ◽  
Standardized Treatment ◽  
Mdr Tb ◽  
Small Cohort ◽  
Health Organization

Abstract Bedaquiline was recommended by the World Health Organization as the preferred option in treatment of multidrug-resistant tuberculosis (MDR-TB) with long regimens. However, no recommendation was given for the short MDR-TB regimen. Data from our small cohort of patients who switched from injectable drug to bedaquiline suggest that a bedaquiline-based short regimen is effective and safe.

scholarly journals Factors associated with multi-drug-resistant tuberculosis in Dakar, Senegal, 2010-2016

2020 ◽  
Vol 10 (2) ◽  
Author(s):  
Mbouna Ndiaye ◽  
Pauline Kiswendsida Yanogo ◽  
Bernard Sawadogo ◽  
Fadima Diallo ◽  
Simon Antara ◽  
...  
Keyword(s):  
Previous Treatment ◽  
Multidrug Resistant ◽  
World Health ◽  
Factors Associated ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Multi Drug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Health Organization ◽  
And Control

According to the World Health Organization, multidrug-resistant tuberculosis (MDR-TB) represents a major obstacle towards successful TB treatment and control. In Dakar, MDR-TB management began in 2010 with the strengthening of diagnostic resources. The objective of this study was to identify the factors associated with multidrug-resistant tuberculosis in Dakar between 2010 and 2016. We conducted a case-control study from January 10 to February 28, 2017 in tuberculosis centers in Dakar. of 169 cases and 507 controls. We used logistic regression with Epi-info version 7.2.1. to estimate the odds ratios of association. Factors significantly associated with MDR-TB were: residing in a periurban area (ORa=1.8; 95% CI (1.5-4.9); p=0.024), presence of MDR-TB in the entourage of patient (ORa=7.0; 95% CI (6.1-9.5); p=0.002), previous treatment failure (ORa=29.5; 95% CI (27.3-30.1); p=0.000), treatment not directly observed by a health care provider (ORa=4.3; 95% CI (4.1-7,2); p=0.000) and irregularity of treatment (ORa=1.7; 95% CI (0.5-5.4); p=0.037). Focusing interventions on population at-risk will prevent MDR-TB.

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