Bedaquiline as a potential agent in the treatment of <i>M. intracellulare</i> and <i>M. avium</i> infections

Vesenbeckh, Silvan; Schönfeld, Nicolas; Krieger, David; Bettermann, Gudrun; Bauer, Torsten T.; Rüssmann, Holger; Mauch, H.

doi:10.1183/13993003.01969-2016

Cited by 19 publications

(13 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The drug was developed to treat multidrug-resistant tuberculosis and has good efficacy and safety when used in combination with the World Health Organization's recommended background regimen for multidrug-resistant tuberculosis. Bedaquiline has also shown potent antimycobacterial activity against MAC, with a low minimal inhibitory concentration in clinical isolates7374. Only one case series has been published for NTM-PD, which included 10 patients (six with MAC and four with M. abscessus ) with refractory NTM-PD and which showed a microbiologic response in 60% of patients and one or more negative cultures in 50% of patients75.…”

Section: Novel Therapeutic Agentsmentioning

confidence: 99%

Treatment ofMycobacterium aviumComplex Pulmonary Disease

2019

View full text Add to dashboard Cite

The pathogen Mycobacterium avium complex (MAC) is the most common cause of nontuberculous mycobacterial pulmonary disease worldwide. The decision to initiate long-term antibiotic treatment is difficult for the physician due to inconsistent disease progression and adverse effects associated with the antibiotic treatment. The prognostic factors for the progression of MAC pulmonary disease are low body mass index, poor nutritional status, presence of cavitary lesion(s), extensive disease, and a positive acid-fast bacilli smear. A regimen consisting of macrolides (clarithromycin or azithromycin) with rifampin and ethambutol has been recommended; this regimen significantly improves the treatment of MAC pulmonary disease and should be maintained for at least 12 months after negative sputum culture conversion. However, the rates of default and disease recurrence after treatment completion are still high. Moreover, treatment failure or macrolide resistance can occur, although in some refractory cases, surgical lung resection can improve treatment outcomes. However, surgical resection should be carefully performed in a well-equipped center and be based on a rigorous risk-benefit analysis in a multidisciplinary setting. New therapies, including clofazimine, inhaled amikacin, and bedaquiline, have shown promising results for the treatment of MAC pulmonary disease, especially in patients with treatment failure or macrolide-resistant MAC pulmonary disease. However, further evidence of the efficacy and safety of these new treatment regimens is needed. Also, a new consensus is needed for treatment outcome definitions as widespread use of these definitions could increase the quality of evidence for the treatment of MAC pulmonary disease.

show abstract

Section: Novel Therapeutic Agentsmentioning

confidence: 99%

Treatment ofMycobacterium aviumComplex Pulmonary Disease

2019

View full text Add to dashboard Cite

show abstract

“…Such information has, to date, been quite limited, not just for Europe but globally, and not available for large, representative populations. An interesting debate is ongoing regarding the use of old and new antibiotics to manage NTM [27,28]. DIEL et al [21] found that 54% had begun treatment at the time of diagnosis and 74% received antibiotics at some point during the past 3 years, with 34.5% receiving a standard regimen and 11.8% receiving macrolide monotherapy for at least 6 months.…”

mentioning

confidence: 99%

Nontuberculous mycobacterial pulmonary disease: an increasing burden with substantial costs

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The interaction is then stabilized by an intermolecular H-bond between the dimethylamino group and Glu65 [ 148 ]. BDQ has also been tested against NTM, M. abscessus , which affects cystic fibrosis patients [ 162 ], and against M. avium and M. intracellulare [ 163 ]. Additionally, it was found to be active against M. abscessus in a zebrafish model of infection [ 164 ].…”

Section: Atp Synthasementioning

confidence: 99%

Bioenergetics of Mycobacterium: An Emerging Landscape for Drug Discovery

et al. 2018

View full text Add to dashboard Cite

Mycobacterium tuberculosis (Mtb) exhibits remarkable metabolic flexibility that enables it to survive a plethora of host environments during its life cycle. With the advent of bedaquiline for treatment of multidrug-resistant tuberculosis, oxidative phosphorylation has been validated as an important target and a vulnerable component of mycobacterial metabolism. Exploiting the dependence of Mtb on oxidative phosphorylation for energy production, several components of this pathway have been targeted for the development of new antimycobacterial agents. This includes targeting NADH dehydrogenase by phenothiazine derivatives, menaquinone biosynthesis by DG70 and other compounds, terminal oxidase by imidazopyridine amides and ATP synthase by diarylquinolines. Importantly, oxidative phosphorylation also plays a critical role in the survival of persisters. Thus, inhibitors of oxidative phosphorylation can synergize with frontline TB drugs to shorten the course of treatment. In this review, we discuss the oxidative phosphorylation pathway and development of its inhibitors in detail.

show abstract

Bedaquiline as a potential agent in the treatment of M. intracellulare and M. avium infections

Cited by 19 publications

References 14 publications

Treatment ofMycobacterium aviumComplex Pulmonary Disease

Treatment ofMycobacterium aviumComplex Pulmonary Disease

Nontuberculous mycobacterial pulmonary disease: an increasing burden with substantial costs

Bioenergetics of Mycobacterium: An Emerging Landscape for Drug Discovery

Contact Info

Product

Resources

About