Bedaquiline as part of combination therapy in adults with pulmonary multi-drug resistant tuberculosis.
BACKGROUND
Few innovative anti-microbial products have been brought to market in recent years to combat the global multidrug resistant-tuberculosis (MDR-TB) epidemic. Bedaquiline, a novel oral diarylquinoline, was approved by the US FDA as a part of combination therapy in adults with pulmonary MDR-TB based on phase II trials.


METHODS
Pubmed searches were conducted using search terms bedaquiline, diarylquinoline, R207910, and TMC207 was performed. Supplementary sources included World Health Organization, Clinicaltrial.gov, US Food and Drug Administration. Bedaquiline is an ATP synthase inhibitor specific for M. tuberculosis and some nontuberculous mycobacteria. It is metabolized by CYP3A4 and it's drug exposure can be influenced by inducers and inhibitors of this enzyme. Phase II studies showed promising results on efficacy of bedaquiline when being used in combination with a background regimen for MDR-TB. Main safety concerns include QTc prolongation and hepatotoxicity. Phase III trials are ongoing to confirm efficacy findings from phase II studies and provide additional evidence of safety and efficacy. Expert commentary: Critical data for long-term efficacy and safety are incomplete and scarce, supporting the cautious use of bedaquiline.
a Department of Pharmacological, Medical and Agronomical Biotechnology , University of Science and Technology of Hanoi , Hanoi , Vietnam.
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TV
Nguyen
b Department of Clinical Pharmacy , Hanoi University of Pharmacy , Hanoi , Vietnam.
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TB
Cao
c University of Groningen, University Medical Center Groningen , Department Pulmonary Diseases and Tuberculosis , Groningen , The Netherlands.|d University of Groningen, University Medical Center Groningen, Tuberculosis Center Beatrixoord , Haren , The Netherlands.
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OW
Akkerman
e Division of Infection , Barts Health NHS Trust , London , UK.
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S
Tiberi
b Department of Clinical Pharmacy , Hanoi University of Pharmacy , Hanoi , Vietnam.
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DH
Vu
f University of Groningen, University Medical Center Groningen, Clinical Pharmacy and Pharmacology , Groningen , The Netherlands.
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JW
Alffenaar
D000284:Administration, Oral; D000328:Adult; D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D051544:Cytochrome P-450 CYP3A / Q000187:drug effects / Q000378:metabolism; D064687:Diarylquinolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000302:isolation & purification; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000382:microbiology
D000995:Antitubercular Agents; D064687:Diarylquinolines; C493870:bedaquiline; D051544:Cytochrome P-450 CYP3A
Bedaquiline; Mycobacterium tuberculosis; anti-tuberculosis drugs; multidrug-resistant tuberculosis; pharmacodynamics; pharmacokinetics