uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
A bedaquiline/clofazimine combination regimen might add activity to the treatment of clinically relevant non-tuberculous mycobacteria
Radboud Univ Nijmegen, Dept Med Microbiol, Med Ctr, Nijmegen, Netherlands.
Radboud Univ Nijmegen, Dept Med Microbiol, Med Ctr, Nijmegen, Netherlands.
Radboud Univ Nijmegen, Dept Med Microbiol, Med Ctr, Nijmegen, Netherlands.
Radboud Univ Nijmegen, Dept Med Microbiol, Med Ctr, Nijmegen, Netherlands.
Show others and affiliations
2019 (English)In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 74, no 4, p. 935-943Article in journal (Refereed) Published
Abstract [en]

Background: Non-tuberculous mycobacteria (NTM) infections are hard to treat. New antimicrobial drugs and smarter combination regimens are needed.

Objectives: Our aim was to determine the in vitro activity of bedaquiline against NTM and assess its synergy with established antimycobacterials.

Methods: We determined MICs of bedaquiline for clinically relevant NTM species and Mycobacterium tuberculosis by broth microdilution for 30 isolates. Synergy testing was performed using the chequerboard method for 22 reference strains and clinical isolates of Mycobacterium abscessus (MAB) and Mycobacterium avium complex (MAC). Time-kill kinetics (TK) assays with resistance monitoring of bedaquiline alone and combined with clofazimine were performed for MAB CIP 104536 and M. avium ATCC 700898; bedaquiline/clarithromycin combinations were evaluated against M. avium ATCC 700898. Interactions were assessed for TK experiments based on Bliss independence.

Results: Bedaquiline had modest activity against tested NTM, with MICs between <0.007and 1mg/L. Bedaquiline showed no interaction with tested drugs against MAB or MAC. Lowest mean fractional inhibitory concentration index (FICI) values were 0.79 with clofazimine for MAB and 0.97 with clofazimine and 0.82 with clarithromycin for MAC. In TK assays, bedaquiline showed a bacteriostatic effect. Clofazimine extended the bacteriostatic activity of bedaquiline against MAB and yielded a slight bactericidal effect against M. avium. The bedaquiline/clofazimine combination slowed emergence of bedaquiline resistance for M. avium but promoted it for MAB. Relative to Bliss independence, bedaquiline/clofazimine showed synergistic interaction over time for MAB and no interaction for M. avium and bedaquiline/clarithromycin showed antagonistic interaction for M. avium.

Conclusions: Following these in vitro data, a bedaquiline/clofazimine combination might add activity to MAB and MAC treatment. The bedaquiline/clarithromycin combination might have lower activity compared with bedaquiline alone for MAC treatment.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS , 2019. Vol. 74, no 4, p. 935-943
National Category
Microbiology in the medical area
Identifiers
URN: urn:nbn:se:uu:diva-382393DOI: 10.1093/jac/dky526ISI: 000463812100013PubMedID: 30649327OAI: oai:DiVA.org:uu-382393DiVA, id: diva2:1307198
Available from: 2019-04-26 Created: 2019-04-26 Last updated: 2019-04-26Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Authority records BETA

Svensson, Elin

Search in DiVA

By author/editor
Svensson, Elin
By organisation
Department of Pharmaceutical Biosciences
In the same journal
Journal of Antimicrobial Chemotherapy
Microbiology in the medical area

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 195 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf