Repositioning rifamycins for Mycobacterium abscessus lung disease
Uday S. Ganapathy, Véronique Dartois & Thomas Dick ORCID Icon
Received 30 Apr 2019, Accepted 05 Jun 2019, Published online: 14 Jun 2019
Download citation https://doi.org/10.1080/17460441.2019.1629414
In this article
ABSTRACT
1. Introduction
2. Rifampicin vs M.abscessus : a TB killer meets its match
3. Rifabutin: a new hope
4. Bacterial cell pharmacokinetics: an explanation for rifabutin’s potency?
5. Partners in crime: harnessing antibacterial drug synergies
6. The home advantage: applying host-directed therapy
7. Conclusion
8. Expert opinion
References
ABSTRACT
Introduction: The treatment of Mycobacterium abscessus lung disease faces significant challenges due to intrinsic antibiotic resistance. New drugs are needed to cure this incurable disease. The key anti-tubercular rifamycin, rifampicin, suffers from low potency against M. abscessus and is not used clinically. Recently, another member of the rifamycin class, rifabutin, was shown to be active against the opportunistic pathogen.
Areas covered: In this review, the authors discuss the rifamycins as a reemerging drug class for treating M. abscessus infections. The authors focus on the differential potency of rifampicin and rifabutin against M. abscessus in the context of intrinsic antibiotic resistance and bacterial uptake and metabolism. Reports of rifamycin-based drug synergies and rifamycin potentiation by host-directed therapy are evaluated.
Expert opinion: While repurposing rifabutin for M. abscessus lung disease may provide some immediate relief, the repositioning (chemical optimization) of rifamycins offers long-term potential for improving clinical outcomes. Repositioning will require a multifaceted approach involving renewed screening of rifamycin libraries, medicinal chemistry to improve ‘bacterial cell pharmacokinetics’, better models of bacterial pathophysiology and infection, and harnessing of drug synergies and host-directed therapy towards the development of a better drug regimen.
KEYWORDS: Lung disease, Mycobacterium abscessus, non-tuberculous mycobacteria, repositioning, rifamycins
Uday S. Ganapathy, Véronique Dartois & Thomas Dick ORCID Icon
Received 30 Apr 2019, Accepted 05 Jun 2019, Published online: 14 Jun 2019
Download citation https://doi.org/10.1080/17460441.2019.1629414
In this article
ABSTRACT
1. Introduction
2. Rifampicin vs M.abscessus : a TB killer meets its match
3. Rifabutin: a new hope
4. Bacterial cell pharmacokinetics: an explanation for rifabutin’s potency?
5. Partners in crime: harnessing antibacterial drug synergies
6. The home advantage: applying host-directed therapy
7. Conclusion
8. Expert opinion
References
ABSTRACT
Introduction: The treatment of Mycobacterium abscessus lung disease faces significant challenges due to intrinsic antibiotic resistance. New drugs are needed to cure this incurable disease. The key anti-tubercular rifamycin, rifampicin, suffers from low potency against M. abscessus and is not used clinically. Recently, another member of the rifamycin class, rifabutin, was shown to be active against the opportunistic pathogen.
Areas covered: In this review, the authors discuss the rifamycins as a reemerging drug class for treating M. abscessus infections. The authors focus on the differential potency of rifampicin and rifabutin against M. abscessus in the context of intrinsic antibiotic resistance and bacterial uptake and metabolism. Reports of rifamycin-based drug synergies and rifamycin potentiation by host-directed therapy are evaluated.
Expert opinion: While repurposing rifabutin for M. abscessus lung disease may provide some immediate relief, the repositioning (chemical optimization) of rifamycins offers long-term potential for improving clinical outcomes. Repositioning will require a multifaceted approach involving renewed screening of rifamycin libraries, medicinal chemistry to improve ‘bacterial cell pharmacokinetics’, better models of bacterial pathophysiology and infection, and harnessing of drug synergies and host-directed therapy towards the development of a better drug regimen.
KEYWORDS: Lung disease, Mycobacterium abscessus, non-tuberculous mycobacteria, repositioning, rifamycins
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