Population Pharmacokinetic Analysis of Bedaquiline-Clarithromycin for Dose Selection Against Pulmonary Nontuberculous Mycobacteria Based on a Phase 1, Randomized, Pharmacokinetic Study
J Clin Pharmacol. 2021 May 15. doi: 10.1002/jcph.1887. Online ahead of print.ABSTRACTBased on in vitro profile of bedaquiline against mycobacterial species, it is being investigated for clinical efficacy against pulmonary nontuberculous mycobacteria (PNTM). Being a cytochrome P450 (CYP) 3A substrate, pharmacokinetic interactions of bedaquiline are anticipated with clarithromycin (a CYP3A inhibitor), which is routinely used in PNTM treatment. This Phase 1, randomized, crossover study assessed the impact of steady-state clarithromycin (500 mg every 12 hours; 14 days) on the pharmacokinetics of bedaquiline and its metabolite ...
Source: The Journal of Clinical Pharmacology - May 15, 2021 Category: Drugs & Pharmacology Authors: Ken Kurosawa Stefaan Rossenu Jeike Biewenga Sivi Ouwerkerk-Mahadevan Wouter Willems Etienne Ernault Chrispin Kambili Source Type: research

Bedaquiline, an FDA-approved drug, inhibits mitochondrial ATP production and metastasis in vivo, by targeting the gamma subunit (ATP5F1C) of the ATP synthase
Cell Death & Differentiation, Published online: 13 May 2021; doi:10.1038/s41418-021-00788-xBedaquiline, an FDA-approved drug, inhibits mitochondrial ATP production and metastasis in vivo, by targeting the gamma subunit (ATP5F1C) of the ATP synthase (Source: Cell Death and Differentiation)
Source: Cell Death and Differentiation - May 13, 2021 Category: Cytology Authors: Marco Fiorillo Cristian Scatena Antonio Giuseppe Naccarato Federica Sotgia Michael P. Lisanti Source Type: research

Low Rate of Acquired Linezolid Resistance in Multidrug-Resistant Tuberculosis Treated With Bedaquiline-Linezolid Combination
In this retrospective study in China, we aimed to: (1) determine the prevalence of linezolid (LZD) resistance among multidrug-resistant tuberculosis (MDR-TB)-infected patients; (2) monitor for dynamic LZD susceptibility changes during anti-TB treatment; and (3) explore molecular mechanisms conferring LZD resistance. A total of 277 MDR-TB patients receiving bedaquiline (BDQ)-containing regimens in 13 TB specialized hospitals across China were enrolled in the study. LZD and BDQ susceptibility rates were determined using the minimum inhibitory concentration (MIC) method, then DNA sequences of patient isolates were analyzed us...
Source: Frontiers in Microbiology - May 3, 2021 Category: Microbiology Source Type: research

A systematic review of pharmacoeconomic evaluations on oral diarylquinoline-based treatment for drug-resistant tuberculosis: from high to low burden countries
This article systematically reviewed publications retrieved from Medline, American Psychological Association-Psychology information, Web of Science, Embase, Scopus, Science direct, Centre for Reviews and Dissemination, and CINAHL Complete during 2010-2020 on pharmacoeconomic studies on BDQ for DR-TB treatment. Ten Markov model-based cost-effectiveness analyses identified were conducted in high (n=4), intermediate (n=2), and low (n=4) TB burden countries.EXPERT OPINION: The paucity of model-based health economic analyses on BDQ-containing regimens for DR-TB indicated that further pharmacoeconomic research of BDQ-based regim...
Source: Expert Review of Pharmacoeconomics and Outcomes Research - May 1, 2021 Category: Health Management Authors: Ginenus Fekadu Jiaqi Yao Joyce H S You Source Type: research

Dual mTORC1/mTORC2 inhibition as a Host-Directed Therapeutic Target in Pathologically Distinct Mouse Models of Tuberculosis
Antimicrob Agents Chemother. 2021 Apr 26:AAC.00253-21. doi: 10.1128/AAC.00253-21. Online ahead of print.ABSTRACTEfforts to develop more effective and shorter-course therapies for tuberculosis have included a focus on host-directed therapy (HDT). The goal of HDT is to modulate the host response to infection, thereby improving immune defenses to reduce the duration of antibacterial therapy and/or the amount of lung damage. As a mediator of innate and adaptive immune responses involved in eliminating intracellular pathogens, autophagy is a potential target for HDT in tuberculosis. Because Mycobacterium tuberculosis modulates ...
Source: Antimicrobial Agents and Chemotherapy - April 27, 2021 Category: Microbiology Authors: Rokeya Tasneen Deborah S Mortensen Paul J Converse Michael E Urbanowski Anna Upton Nader Fotouhi Eric Nuermberger Natalie Hawryluk Source Type: research

Dual mTORC1/mTORC2 inhibition as a Host-Directed Therapeutic Target in Pathologically Distinct Mouse Models of Tuberculosis
Antimicrob Agents Chemother. 2021 Apr 26:AAC.00253-21. doi: 10.1128/AAC.00253-21. Online ahead of print.ABSTRACTEfforts to develop more effective and shorter-course therapies for tuberculosis have included a focus on host-directed therapy (HDT). The goal of HDT is to modulate the host response to infection, thereby improving immune defenses to reduce the duration of antibacterial therapy and/or the amount of lung damage. As a mediator of innate and adaptive immune responses involved in eliminating intracellular pathogens, autophagy is a potential target for HDT in tuberculosis. Because Mycobacterium tuberculosis modulates ...
Source: Antimicrobial Agents and Chemotherapy - April 27, 2021 Category: Microbiology Authors: Rokeya Tasneen Deborah S Mortensen Paul J Converse Michael E Urbanowski Anna Upton Nader Fotouhi Eric Nuermberger Natalie Hawryluk Source Type: research

Dual mTORC1/mTORC2 inhibition as a Host-Directed Therapeutic Target in Pathologically Distinct Mouse Models of Tuberculosis
Antimicrob Agents Chemother. 2021 Apr 26:AAC.00253-21. doi: 10.1128/AAC.00253-21. Online ahead of print.ABSTRACTEfforts to develop more effective and shorter-course therapies for tuberculosis have included a focus on host-directed therapy (HDT). The goal of HDT is to modulate the host response to infection, thereby improving immune defenses to reduce the duration of antibacterial therapy and/or the amount of lung damage. As a mediator of innate and adaptive immune responses involved in eliminating intracellular pathogens, autophagy is a potential target for HDT in tuberculosis. Because Mycobacterium tuberculosis modulates ...
Source: Antimicrobial Agents and Chemotherapy - April 27, 2021 Category: Microbiology Authors: Rokeya Tasneen Deborah S Mortensen Paul J Converse Michael E Urbanowski Anna Upton Nader Fotouhi Eric Nuermberger Natalie Hawryluk Source Type: research

Dual mTORC1/mTORC2 inhibition as a Host-Directed Therapeutic Target in Pathologically Distinct Mouse Models of Tuberculosis
Antimicrob Agents Chemother. 2021 Apr 26:AAC.00253-21. doi: 10.1128/AAC.00253-21. Online ahead of print.ABSTRACTEfforts to develop more effective and shorter-course therapies for tuberculosis have included a focus on host-directed therapy (HDT). The goal of HDT is to modulate the host response to infection, thereby improving immune defenses to reduce the duration of antibacterial therapy and/or the amount of lung damage. As a mediator of innate and adaptive immune responses involved in eliminating intracellular pathogens, autophagy is a potential target for HDT in tuberculosis. Because Mycobacterium tuberculosis modulates ...
Source: Antimicrobial Agents and Chemotherapy - April 27, 2021 Category: Microbiology Authors: Rokeya Tasneen Deborah S Mortensen Paul J Converse Michael E Urbanowski Anna Upton Nader Fotouhi Eric Nuermberger Natalie Hawryluk Source Type: research

Dual mTORC1/mTORC2 inhibition as a Host-Directed Therapeutic Target in Pathologically Distinct Mouse Models of Tuberculosis
Antimicrob Agents Chemother. 2021 Apr 26:AAC.00253-21. doi: 10.1128/AAC.00253-21. Online ahead of print.ABSTRACTEfforts to develop more effective and shorter-course therapies for tuberculosis have included a focus on host-directed therapy (HDT). The goal of HDT is to modulate the host response to infection, thereby improving immune defenses to reduce the duration of antibacterial therapy and/or the amount of lung damage. As a mediator of innate and adaptive immune responses involved in eliminating intracellular pathogens, autophagy is a potential target for HDT in tuberculosis. Because Mycobacterium tuberculosis modulates ...
Source: Antimicrobial Agents and Chemotherapy - April 27, 2021 Category: Microbiology Authors: Rokeya Tasneen Deborah S Mortensen Paul J Converse Michael E Urbanowski Anna Upton Nader Fotouhi Eric Nuermberger Natalie Hawryluk Source Type: research

Dual mTORC1/mTORC2 inhibition as a Host-Directed Therapeutic Target in Pathologically Distinct Mouse Models of Tuberculosis
Antimicrob Agents Chemother. 2021 Apr 26:AAC.00253-21. doi: 10.1128/AAC.00253-21. Online ahead of print.ABSTRACTEfforts to develop more effective and shorter-course therapies for tuberculosis have included a focus on host-directed therapy (HDT). The goal of HDT is to modulate the host response to infection, thereby improving immune defenses to reduce the duration of antibacterial therapy and/or the amount of lung damage. As a mediator of innate and adaptive immune responses involved in eliminating intracellular pathogens, autophagy is a potential target for HDT in tuberculosis. Because Mycobacterium tuberculosis modulates ...
Source: Antimicrobial Agents and Chemotherapy - April 27, 2021 Category: Microbiology Authors: Rokeya Tasneen Deborah S Mortensen Paul J Converse Michael E Urbanowski Anna Upton Nader Fotouhi Eric Nuermberger Natalie Hawryluk Source Type: research

Unveiling p-Quinone methide (QM) chemistry to synthesize Bedaquiline (TMC 207) like architectures
Publication date: Available online 24 April 2021Source: Journal of Molecular StructureAuthor(s): Deblina Roy, Kasim Ali, Gautam Panda (Source: Journal of Molecular Structure)
Source: Journal of Molecular Structure - April 25, 2021 Category: Molecular Biology Source Type: research

Outcomes of Children Born to Pregnant Women With Drug-resistant Tuberculosis Treated With Novel Drugs in Khayelitsha, South Africa: A Report of Five Patients
This brief report presents a series of 5 pregnant women treated for rifampicin-resistant tuberculosis with the novel drugs bedaquiline, delamanid, and linezolid as part of an optimized backbone regimen and reviews the outcomes of the children born to them. Although the case series is small, all children had excellent birth outcomes suggesting pregnant women should not be denied access to novel therapies for RR-TB. (Source: The Pediatric Infectious Disease Journal)
Source: The Pediatric Infectious Disease Journal - April 19, 2021 Category: Infectious Diseases Tags: Maternal-Neonatal Reports Source Type: research

A disseminated Mycobacterium marinum infection in a renal transplant HIV-infected patient successfully treated with a bedaquiline-containing antimycobacterial treatment: a case report
We reported a case of Mycobacterium Marinum disseminated infection in a 54 year-old renal transplant HIV-infected woman. (Source: International Journal of Infectious Diseases)
Source: International Journal of Infectious Diseases - April 16, 2021 Category: Infectious Diseases Authors: Agn ès Meybeck, Macha Tetart, Véronique Baclet, Isabelle Alcaraz, Nicolas Blondiaux, Gilles Peytavin, Nicolas Veyziris, Olivier Robineau, Eric Senneville Tags: Case Report Source Type: research

Repurposing Immunomodulatory Drugs to Combat Tuberculosis
Tuberculosis (TB) is an infectious disease caused by an obligate intracellular pathogen, Mycobacterium tuberculosis (M.tb) and is responsible for the maximum number of deaths due to a single infectious agent. Current therapy for TB, Directly Observed Treatment Short-course (DOTS) comprises multiple antibiotics administered in combination for 6 months, which eliminates the bacteria and prevents the emergence of drug-resistance in patients if followed as prescribed. However, due to various limitations viz., severe toxicity, low efficacy and long duration; patients struggle to comply with the prescribed therapy, whi...
Source: Frontiers in Immunology - April 13, 2021 Category: Allergy & Immunology Source Type: research

Atypical mycobacterial infections – management and when to treat
Purpose of review Infections caused by nontuberculous mycobacteria (NTM) are increasing for several reasons, including diagnostic advances, increased awareness and a larger at-risk population. NTM pulmonary disease is surpassing tuberculosis (TB) in some low incidence areas. This review summarizes the latest literature and guidelines and aims to be a concise source outlining treatment and management of NTM lung infections, integrating established treatment paradigms with novel pharmacological interventions. Recent findings Recent additions to NTM treatment are inhaled liposomal amikacin and the anti-TB drug beda...
Source: Current Opinion in Pulmonary Medicine - April 10, 2021 Category: Respiratory Medicine Tags: INFECTIOUS DISEASES: Edited by Michael S. Niederman and Alimuddin Zumla Source Type: research

The Treatment of Tuberculosis
Clin Pharmacol Ther. 2021 Apr 10. doi: 10.1002/cpt.2261. Online ahead of print.ABSTRACTTuberculosis (TB) remains a leading cause of infectious death worldwide, and poverty is a major driver. Clinically, TB presents as "latent" TB and active TB disease, and the treatment for each is different. TB drugs can display "early bactericidal activity (EBA)" and / or "sterilizing activity" (clearing persisters). Isoniazid is excellent at the former, and rifampin is excellent at the latter. Pyrazinamide and ethambutol complete the first-line regimen for drug-susceptible TB, each playing a specific role. ...
Source: Clinical Pharmacology and Therapeutics - April 10, 2021 Category: Drugs & Pharmacology Authors: Charles A Peloquin Geraint R Davies Source Type: research

The Treatment of Tuberculosis
Clin Pharmacol Ther. 2021 Apr 10. doi: 10.1002/cpt.2261. Online ahead of print.ABSTRACTTuberculosis (TB) remains a leading cause of infectious death worldwide, and poverty is a major driver. Clinically, TB presents as "latent" TB and active TB disease, and the treatment for each is different. TB drugs can display "early bactericidal activity (EBA)" and / or "sterilizing activity" (clearing persisters). Isoniazid is excellent at the former, and rifampin is excellent at the latter. Pyrazinamide and ethambutol complete the first-line regimen for drug-susceptible TB, each playing a specific role. ...
Source: Clinical Pharmacology and Therapeutics - April 10, 2021 Category: Drugs & Pharmacology Authors: Charles A Peloquin Geraint R Davies Source Type: research

The Treatment of Tuberculosis
Clin Pharmacol Ther. 2021 Apr 10. doi: 10.1002/cpt.2261. Online ahead of print.ABSTRACTTuberculosis (TB) remains a leading cause of infectious death worldwide, and poverty is a major driver. Clinically, TB presents as "latent" TB and active TB disease, and the treatment for each is different. TB drugs can display "early bactericidal activity (EBA)" and / or "sterilizing activity" (clearing persisters). Isoniazid is excellent at the former, and rifampin is excellent at the latter. Pyrazinamide and ethambutol complete the first-line regimen for drug-susceptible TB, each playing a specific role. ...
Source: Clinical Pharmacology and Therapeutics - April 10, 2021 Category: Drugs & Pharmacology Authors: Charles A Peloquin Geraint R Davies Source Type: research

The Treatment of Tuberculosis
Clin Pharmacol Ther. 2021 Apr 10. doi: 10.1002/cpt.2261. Online ahead of print.ABSTRACTTuberculosis (TB) remains a leading cause of infectious death worldwide, and poverty is a major driver. Clinically, TB presents as "latent" TB and active TB disease, and the treatment for each is different. TB drugs can display "early bactericidal activity (EBA)" and / or "sterilizing activity" (clearing persisters). Isoniazid is excellent at the former, and rifampin is excellent at the latter. Pyrazinamide and ethambutol complete the first-line regimen for drug-susceptible TB, each playing a specific role. ...
Source: Clinical Pharmacology and Therapeutics - April 10, 2021 Category: Drugs & Pharmacology Authors: Charles A Peloquin Geraint R Davies Source Type: research

Molecular characterization of multidrug-resistant tuberculosis against levofloxacin, moxifloxacin, bedaquiline, linezolid, clofazimine, and delamanid in southwest of China
To explore the drug susceptibility of levofloxacin (LFX), moxifloxacin (MFX), bedaquiline (BDQ), linezolid (LZD), clofazimine (CFZ) and delamanid (DLM) against multidrug resistant tuberculosis (MDR-TB) isolate... (Source: BMC Infectious Diseases)
Source: BMC Infectious Diseases - April 8, 2021 Category: Infectious Diseases Authors: Huiwen Zheng, Wencong He, Weiwei Jiao, Hui Xia, Lin Sun, Shengfen Wang, Jing Xiao, Xichao Ou, Yanlin Zhao and Adong Shen Tags: Research article Source Type: research

Culture conversion at six months in patients receiving bedaquiline- and delamanid-containing regimens for the treatment of multidrug-resistant tuberculosis
(Source: International Journal of Infectious Diseases)
Source: International Journal of Infectious Diseases - April 3, 2021 Category: Infectious Diseases Authors: Shynar M. Maretbayeva, Anar S. Rakisheva, Malik M. Adenov, Lyazzat T. Yeraliyeva, Yerkebulan Zh. Algozhin, Assel T. Stambekova, Elmira A. Berikova, Askar Yedilbayev, Michael L. Rich, Kwonjune J. Seung, Assiya M. Issayeva Source Type: research

Erratum: Culture Conversion in Patients Treated with Bedaquiline and/or Delamanid: A Prospective Multicountry Study
Am J Respir Crit Care Med. 2021 Apr 1;203(7):929. doi: 10.1164/rccm.v203erratum6.NO ABSTRACTPMID:33792533 | PMC:PMC8017571 | DOI:10.1164/rccm.v203erratum6 (Source: American Journal of Respiratory and Critical Care Medicine)
Source: American Journal of Respiratory and Critical Care Medicine - April 1, 2021 Category: Respiratory Medicine Source Type: research

Erratum: Culture Conversion in Patients Treated with Bedaquiline and/or Delamanid: A Prospective Multicountry Study
Am J Respir Crit Care Med. 2021 Apr 1;203(7):929. doi: 10.1164/rccm.v203erratum6.NO ABSTRACTPMID:33792533 | PMC:PMC8017571 | DOI:10.1164/rccm.v203erratum6 (Source: Am J Respir Crit Car...)
Source: Am J Respir Crit Car... - April 1, 2021 Category: Intensive Care Source Type: research

Erratum: Culture Conversion in Patients Treated with Bedaquiline and/or Delamanid: A Prospective Multicountry Study
Am J Respir Crit Care Med. 2021 Apr 1;203(7):929. doi: 10.1164/rccm.v203erratum6.NO ABSTRACTPMID:33792533 | DOI:10.1164/rccm.v203erratum6 (Source: Am J Respir Crit Car...)
Source: Am J Respir Crit Car... - April 1, 2021 Category: Intensive Care Source Type: research

Erratum: Culture Conversion in Patients Treated with Bedaquiline and/or Delamanid: A Prospective Multicountry Study
Am J Respir Crit Care Med. 2021 Apr 1;203(7):929. doi: 10.1164/rccm.v203erratum6.NO ABSTRACTPMID:33792533 | DOI:10.1164/rccm.v203erratum6 (Source: Respiratory Care)
Source: Respiratory Care - April 1, 2021 Category: Respiratory Medicine Source Type: research

Erratum: Culture Conversion in Patients Treated with Bedaquiline and/or Delamanid: A Prospective Multicountry Study
Am J Respir Crit Care Med. 2021 Apr 1;203(7):929. doi: 10.1164/rccm.v203erratum6.NO ABSTRACTPMID:33792533 | DOI:10.1164/rccm.v203erratum6 (Source: American Journal of Respiratory and Critical Care Medicine)
Source: American Journal of Respiratory and Critical Care Medicine - April 1, 2021 Category: Respiratory Medicine Source Type: research

Maleate salts of bedaquiline
We present here five crystal structures of bedaquilinium maleate {systematic name: [4-(6-bromo-2-methoxyquinolin-3-yl)-3-hydroxy-3-(naphthalen-1-yl)-4-phenylbutyl]dimethylazanium 3-carboxyprop-2-enoate}, C32H32BrN2O2+ · C4H3O4 − , namely, a hemihydrate, a tetrahydrofuran (THF) solvate, a mixed acetone/hexane solvate, an ethyl acetate solvate, and a solvate-free structure obtained from the acetone/hexane solvate by in situ single-crystal-to-single-crystal desolvation. All salts exhibit a 1:1 cation-to-anion ratio, with the anion present as monoanionic hydromaleate and a singly protonated bedaquilinium cation. T...
Source: Acta Crystallographica Section E - March 26, 2021 Category: Chemistry Authors: Zeller, M. Bogdanowich-Knipp, S. Smith, P. Purcell, D.K. Okezue, M. Smith, D.T. Byrn, S.R. Clase, K.L. Tags: bedaquiline drug-resistant tuberculosis isomorphous organic salts desolvation crystal structure research communications Source Type: research

Mycobactericidal Effects of Different Regimens Measured by Molecular Bacterial Load Assay among People Treated for Multidrug-Resistant Tuberculosis in Tanzania [Mycobacteriology and Aerobic Actinomycetes]
Rifampin or multidrug-resistant tuberculosis (RR/MDR-TB) treatment has largely transitioned to regimens free of the injectable aminoglycoside component, despite the drug class’ purported bactericidal activity early in treatment. We tested whether Mycobacterium tuberculosis killing rates measured by tuberculosis molecular bacterial load assay (TB-MBLA) in sputa correlate with composition of the RR/MDR-TB regimen. Serial sputa were collected from patients with RR/MDR- and drug-sensitive TB at days 0, 3, 7, and 14, and then monthly for 4 months of anti-TB treatment. TB-MBLA was used to quantify viable M. tuberculosis 16...
Source: Journal of Clinical Microbiology - March 19, 2021 Category: Microbiology Authors: Mbelele, P. M., Mpolya, E. A., Sauli, E., Mtafya, B., Ntinginya, N. E., Addo, K. K., Kreppel, K., Mfinanga, S., Phillips, P. P. J., Gillespie, S. H., Heysell, S. K., Sabiiti, W., Mpagama, S. G. Tags: Mycobacteriology and Aerobic Actinomycetes Source Type: research

Bedaquiline-containing regimens in patients with pulmonary multidrug-resistant tuberculosis in China: focus on the safety
ConclusionsBedaquiline was generally well-tolerated with few safety concerns in this clinical patient population without any new safety signal identified. The mortality rate was generally low. These data inform significant positive effect to support the WHO recent recommendations for the wide use of bedaquiline. (Source: Infectious Diseases of Poverty)
Source: Infectious Diseases of Poverty - March 19, 2021 Category: Infectious Diseases Source Type: research

Bedaquiline: current status and future perspectives
Publication date: Available online 5 March 2021Source: Journal of Global Antimicrobial ResistanceAuthor(s): Saeed Khoshnood, Mehdi Goudarzi, Elahe Taki, Atieh Darbandi, Ebrahim Kouhsari, Mohsen Heidary, Moloudsadat Motahar, Melika Moradi, Hadi Bazyar (Source: Journal of Global Antimicrobial Resistance)
Source: Journal of Global Antimicrobial Resistance - March 6, 2021 Category: Infectious Diseases Source Type: research

Concurrent use of bedaquiline and delamanid for the treatment of fluoroquinolone-resistant multidrug-resistant tuberculosis: a nationwide cohort study in South Korea
This study analysed the efficacy and safety of concurrent use of Bdq and Dlm in patients with MDR-TB and XDR-TB treated under a programmatic condition. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 4, 2021 Category: Respiratory Medicine Authors: Kwon, Y.-S., Jeon, D., Kang, H., Yim, J.-J., Shim, T. S. Tags: Original Articles: Research letters Source Type: research

Submission for Special Issue: The Role of Platelet Activation in the Pathophysiology of HIV, Tuberculosis, and Pneumococcal Disease. Bedaquiline Suppresses ADP-Mediated Activation of Human Platelets In Vitro via Interference With Phosphatidylinositol 3-Kinase
Although bedaquiline has advanced the treatment of multidrug-resistant tuberculosis (TB), concerns remain about the cardiotoxic potential of this agent, albeit by unexplored mechanisms. Accordingly, we have investigated augmentation of the reactivity of human platelets in vitro as a potential mechanism of bedaquiline-mediated cardiotoxicity. Platelet-rich plasma (PRP) or isolated cells prepared from the blood of healthy, adult humans were treated with bedaquiline (0.625–10 µg/ml), followed by activation with adenosine 5’-diphosphate (ADP), thrombin or the thromboxane A2 receptor agonist (U46619). Expressi...
Source: Frontiers in Immunology - February 26, 2021 Category: Allergy & Immunology Source Type: research

In vitro Antibacterial Activity of an FDA-Approved H+-ATPase Inhibitor, Bedaquiline, Against Streptococcus mutans in Acidic Milieus
BackgroundDental caries is an acid-related disease. Current anti-caries agents mainly focus on the bacteriostatic effect in a neutral environment and do not target acid-resistant microorganisms related to caries in acidic milieus.ObjectivesTo assess the in vitro antibacterial activities of bedaquiline against oral pathogens in acidic milieus.MethodsStreptococcus mutans, Streptococcus sanguinis, and Streptococcus salivarius were used to prepare the mono-/multiple suspension and biofilm. The MIC and IC50 of bedaquiline against S. mutans were determined by the broth microdilution method. Bedaquiline was compared regarding (i)...
Source: Frontiers in Microbiology - February 25, 2021 Category: Microbiology Source Type: research

Bedaquiline as Treatment for Disseminated Nontuberculous Mycobacteria Infection in 2 Patients Co-Infected with HIV
We report successful treatment with bedaquiline, a novel antimycobacterial drug, as part of combination therapy for 2 patients with disseminated nontuberculous mycobacteria co-infected with HIV.PMID:33622490 | DOI:10.3201/eid2703.202359 (Source: Emerging Infectious Diseases)
Source: Emerging Infectious Diseases - February 24, 2021 Category: Infectious Diseases Authors: Eliza Gil Nicola Sweeney Veronica Barrett Stephen Morris-Jones Robert F Miller Victoria J Johnston Michael Brown Source Type: research

Limited Capability for Testing Mycobacterium tuberculosis for Susceptibility to New Drugs
Emerg Infect Dis. 2021 Mar;27(3):985-987. doi: 10.3201/eid2703.204418.ABSTRACTWe surveyed availability of phenotypic drug susceptibility testing for drug-resistant Mycobacterium tuberculosis in Europe. Of 27 laboratories, 17 tested for linezolid, 11 for clofazimine, 9 for bedaquiline, and 6 for delamanid during 2019. Our findings indicate that testing capacity for newer and repurposed tuberculosis drugs exists, but its availability is limited.PMID:33622487 | DOI:10.3201/eid2703.204418 (Source: Emerging Infectious Diseases)
Source: Emerging Infectious Diseases - February 24, 2021 Category: Infectious Diseases Authors: Hamzah Z Farooq Daniela M Cirillo Doris Hillemann David Wyllie Marieke J van der Werf Csaba K ödmön Vlad Nikolayevskyy Source Type: research

Bedaquiline as Treatment for Disseminated Nontuberculous Mycobacteria Infection in 2 Patients Co-Infected with HIV
We report successful treatment with bedaquiline, a novel antimycobacterial drug, as part of combination therapy for 2 patients with disseminated nontuberculous mycobacteria co-infected with HIV.PMID:33622490 | DOI:10.3201/eid2703.202359 (Source: Emerging Infectious Diseases)
Source: Emerging Infectious Diseases - February 24, 2021 Category: Infectious Diseases Authors: Eliza Gil Nicola Sweeney Veronica Barrett Stephen Morris-Jones Robert F Miller Victoria J Johnston Michael Brown Source Type: research

Limited Capability for Testing Mycobacterium tuberculosis for Susceptibility to New Drugs
Emerg Infect Dis. 2021 Mar;27(3):985-987. doi: 10.3201/eid2703.204418.ABSTRACTWe surveyed availability of phenotypic drug susceptibility testing for drug-resistant Mycobacterium tuberculosis in Europe. Of 27 laboratories, 17 tested for linezolid, 11 for clofazimine, 9 for bedaquiline, and 6 for delamanid during 2019. Our findings indicate that testing capacity for newer and repurposed tuberculosis drugs exists, but its availability is limited.PMID:33622487 | DOI:10.3201/eid2703.204418 (Source: Emerging Infectious Diseases)
Source: Emerging Infectious Diseases - February 24, 2021 Category: Infectious Diseases Authors: Hamzah Z Farooq Daniela M Cirillo Doris Hillemann David Wyllie Marieke J van der Werf Csaba K ödmön Vlad Nikolayevskyy Source Type: research

Bedaquiline as Treatment for Disseminated Nontuberculous Mycobacteria Infection in 2 Patients Co-Infected with HIV
We report successful treatment with bedaquiline, a novel antimycobacterial drug, as part of combination therapy for 2 patients with disseminated nontuberculous mycobacteria co-infected with HIV.PMID:33622490 | DOI:10.3201/eid2703.202359 (Source: Emerging Infectious Diseases)
Source: Emerging Infectious Diseases - February 24, 2021 Category: Infectious Diseases Authors: Eliza Gil Nicola Sweeney Veronica Barrett Stephen Morris-Jones Robert F Miller Victoria J Johnston Michael Brown Source Type: research

Limited Capability for Testing Mycobacterium tuberculosis for Susceptibility to New Drugs
Emerg Infect Dis. 2021 Mar;27(3):985-987. doi: 10.3201/eid2703.204418.ABSTRACTWe surveyed availability of phenotypic drug susceptibility testing for drug-resistant Mycobacterium tuberculosis in Europe. Of 27 laboratories, 17 tested for linezolid, 11 for clofazimine, 9 for bedaquiline, and 6 for delamanid during 2019. Our findings indicate that testing capacity for newer and repurposed tuberculosis drugs exists, but its availability is limited.PMID:33622487 | DOI:10.3201/eid2703.204418 (Source: Emerging Infectious Diseases)
Source: Emerging Infectious Diseases - February 24, 2021 Category: Infectious Diseases Authors: Hamzah Z Farooq Daniela M Cirillo Doris Hillemann David Wyllie Marieke J van der Werf Csaba K ödmön Vlad Nikolayevskyy Source Type: research

Bedaquiline as Treatment for Disseminated Nontuberculous Mycobacteria Infection in 2 Patients Co-Infected with HIV
We report successful treatment with bedaquiline, a novel antimycobacterial drug, as part of combination therapy for 2 patients with disseminated nontuberculous mycobacteria co-infected with HIV.PMID:33622490 | DOI:10.3201/eid2703.202359 (Source: Emerging Infectious Diseases)
Source: Emerging Infectious Diseases - February 24, 2021 Category: Infectious Diseases Authors: Eliza Gil Nicola Sweeney Veronica Barrett Stephen Morris-Jones Robert F Miller Victoria J Johnston Michael Brown Source Type: research

Limited Capability for Testing Mycobacterium tuberculosis for Susceptibility to New Drugs
Emerg Infect Dis. 2021 Mar;27(3):985-987. doi: 10.3201/eid2703.204418.ABSTRACTWe surveyed availability of phenotypic drug susceptibility testing for drug-resistant Mycobacterium tuberculosis in Europe. Of 27 laboratories, 17 tested for linezolid, 11 for clofazimine, 9 for bedaquiline, and 6 for delamanid during 2019. Our findings indicate that testing capacity for newer and repurposed tuberculosis drugs exists, but its availability is limited.PMID:33622487 | DOI:10.3201/eid2703.204418 (Source: Emerging Infectious Diseases)
Source: Emerging Infectious Diseases - February 24, 2021 Category: Infectious Diseases Authors: Hamzah Z Farooq Daniela M Cirillo Doris Hillemann David Wyllie Marieke J van der Werf Csaba K ödmön Vlad Nikolayevskyy Source Type: research

Bedaquiline as Treatment for Disseminated Nontuberculous Mycobacteria Infection in 2 Patients Co-Infected with HIV
We report successful treatment with bedaquiline, a novel antimycobacterial drug, as part of combination therapy for 2 patients with disseminated nontuberculous mycobacteria co-infected with HIV.PMID:33622490 | DOI:10.3201/eid2703.202359 (Source: Emerging Infectious Diseases)
Source: Emerging Infectious Diseases - February 24, 2021 Category: Infectious Diseases Authors: Eliza Gil Nicola Sweeney Veronica Barrett Stephen Morris-Jones Robert F Miller Victoria J Johnston Michael Brown Source Type: research

Limited Capability for Testing Mycobacterium tuberculosis for Susceptibility to New Drugs
Emerg Infect Dis. 2021 Mar;27(3):985-987. doi: 10.3201/eid2703.204418.ABSTRACTWe surveyed availability of phenotypic drug susceptibility testing for drug-resistant Mycobacterium tuberculosis in Europe. Of 27 laboratories, 17 tested for linezolid, 11 for clofazimine, 9 for bedaquiline, and 6 for delamanid during 2019. Our findings indicate that testing capacity for newer and repurposed tuberculosis drugs exists, but its availability is limited.PMID:33622487 | DOI:10.3201/eid2703.204418 (Source: Emerging Infectious Diseases)
Source: Emerging Infectious Diseases - February 24, 2021 Category: Infectious Diseases Authors: Hamzah Z Farooq Daniela M Cirillo Doris Hillemann David Wyllie Marieke J van der Werf Csaba K ödmön Vlad Nikolayevskyy Source Type: research

Bedaquiline as Treatment for Disseminated Nontuberculous Mycobacteria Infection in 2 Patients Co-Infected with HIV
E. Gil et al. (Source: Emerging Infectious Diseases Journal)
Source: Emerging Infectious Diseases Journal - February 10, 2021 Category: Infectious Diseases Source Type: research

Prevalence and molecular characterizations of seven additional drug resistance among multidrug-resistant tuberculosis in China: a subsequent study of a national survey
Multidrug-resistant tuberculosis (MDR-TB), defined as resistance to at least isoniazid (INH) and rifampicin (RIF), is a major threat to TB control and prevention strategy worldwide.1 Compared with drug-susceptible TB, treatment of MDR-TB requires longer time and more expensive drugs with greater toxicities. 2 The World Health Organization (WHO) recommended key changes to treat multidrug- and RIF-resistant tuberculosis (MDR/RR-TB) in August 2018, 3 and categorized levofloxacin/moxifloxacin (Mfx), bedaquiline (Bdq) and linezolid (Lzd) as Group A (medicines to be prioritized), clofazimine (Cfz), cycloserine (Cs)/terizidone as...
Source: Journal of Infection - February 4, 2021 Category: Infectious Diseases Authors: Guirong Wang, Guanglu Jiang, Wei Jing, Zaojing Zong, Xia Yu, Suting Chen, Weimin Li, Hairong Huang Source Type: research

Comparative efficacy of the novel diarylquinoline TBAJ-587 and bedaquiline against a resistant Rv0678 mutant in a mouse model of tuberculosis.
Abstract Since its conditional approval in 2012, bedaquiline (BDQ) has been a valuable tool for treatment of drug-resistant tuberculosis. More recently, a novel short-course regimen combining BDQ with pretomanid and linezolid won approval to treat highly drug-resistant tuberculosis. Clinical reports of emerging BDQ resistance have identified mutations in Rv0678 that de-repress the expression of the MmpL5/MmpS5 efflux transporter as the most common cause. Because the effect of these mutations on bacterial susceptibility to BDQ is relatively small (e.g., 2-8x MIC shift), increasing the BDQ dose would increase antiba...
Source: Antimicrobial Agents and Chemotherapy - February 1, 2021 Category: Microbiology Authors: Xu J, Converse PJ, Upton AM, Mdluli K, Fotouhi N, Nuermberger EL Tags: Antimicrob Agents Chemother Source Type: research

Interim Effectiveness and Safety Comparison of Bedaquiline-Containing Regimens for Treatment of Diabetic Versus Non-Diabetic MDR/XDR-TB Patients in China: A Multicenter Retrospective Cohort Study
AbstractIntroductionDiabetes mellitus (DM), a common tuberculosis (TB) comorbidity, is associated with delayed bacillary clearance during anti-TB treatment and unfavorable outcomes. Bedaquiline (BDQ), when used as part of multidrug regimen for multidrug-resistant/extensively drug-resistant tuberculosis (MDR/XDR-TB), has been shown to be effective and safe although treatment outcome and risks for patients with MDR/XDR-TB and DM are unknown. A multicenter retrospective study was conducted to compared the safety and effectiveness of 24-week BDQ-containing anti-TB treatment for patients with MDR/XDR-TB with and without DM.Meth...
Source: Infectious Diseases and Therapy - January 30, 2021 Category: Infectious Diseases Source Type: research

The Prospective Synergy of Antitubercular Drugs With NAD Biosynthesis Inhibitors
In conclusion, future strategies targeting NAD metabolism in Mtb should consider its potential synergy with current and other forthcoming TB-drugs. (Source: Frontiers in Microbiology)
Source: Frontiers in Microbiology - January 26, 2021 Category: Microbiology Source Type: research