In vitro and ex vivo activity of the fluoroquinolone DC-159a against mycobacteria

J Antibiot (Tokyo). 2024 May;77(5):306-314. doi: 10.1038/s41429-024-00709-3. Epub 2024 Mar 4.

Abstract

Antimicrobial resistance is a global health problem. In 2021, it was estimated almost half a million of multidrug-resistant tuberculosis (MDR-TB) cases. Besides, non-tuberculous mycobacteria (NTM) are highly resistant to several drugs and the emergence of fluoroquinolone (FQ) resistant M. tuberculosis (Mtb) is also a global concern making treatments difficult and with variable outcome. The aim of this study was to evaluate the activity of the FQ, DC-159a, against Mtb and NTM and to explore the cross-resistance with the currently used FQs.A total of 12 pre-extensively drug-resistant (XDR) Mtb, 2 XDR, 36 fully drug susceptible strains and 41 NTM isolates were included to estimate the in vitro activity of DC-159a, moxifloxacin (MOX) and levofloxacin (LX), using minimal inhibitory and bactericidal concentration (MIC and MBC). The activity inside the human macrophages and pulmonary epithelial cells were also determined.DC-159a was active in vitro and ex vivo against mycobacteria. Besides, it was more active than MOX/LX. Moreover, no cross-resistance was evidenced between DC-159a and LX/MOX as DC-159a could inhibit Mtb and MAC strains that were already resistant to LX/MOX.DC-159a could be a possible candidate in new therapeutic regimens for MDR/ XDR-TB and mycobacterioses cases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopyridines*
  • Anti-Bacterial Agents / pharmacology
  • Antitubercular Agents / pharmacology
  • Drug Resistance, Multiple, Bacterial / drug effects
  • Fluoroquinolones* / pharmacology
  • Humans
  • Levofloxacin / pharmacology
  • Macrophages / drug effects
  • Microbial Sensitivity Tests*
  • Moxifloxacin* / pharmacology
  • Mycobacterium tuberculosis* / drug effects
  • Nontuberculous Mycobacteria / drug effects

Substances

  • Fluoroquinolones
  • Moxifloxacin
  • Antitubercular Agents
  • Levofloxacin
  • 7-(7-amino-7-methyl-5-azaspiro(2.4)heptan-5-yl)-6-fluoro-1-(2-fluoro-1-cyclopropyl)-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid
  • Anti-Bacterial Agents
  • Aminopyridines