Activity of the fluoroquinolone DC-159a in the initial and continuation phases of treatment of murine tuberculosis

Zahoor Ahmad; Austin Minkowski; Charles A Peloquin; Kathy N Williams; Khisimuzi E Mdluli; Jacques H Grosset; Eric L Nuermberger

doi:10.1128/AAC.01514-10

Activity of the fluoroquinolone DC-159a in the initial and continuation phases of treatment of murine tuberculosis

Antimicrob Agents Chemother. 2011 Apr;55(4):1781-3. doi: 10.1128/AAC.01514-10. Epub 2011 Jan 31.

Authors

Zahoor Ahmad¹, Austin Minkowski, Charles A Peloquin, Kathy N Williams, Khisimuzi E Mdluli, Jacques H Grosset, Eric L Nuermberger

Affiliation

¹ Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.

Abstract

DC-159a is a new fluoroquinolone with more potent in vitro activity than available fluoroquinolones against both drug-susceptible and fluoroquinolone-resistant Mycobacterium tuberculosis. Here, we report that DC-159a displays pharmacokinetics similar to those of moxifloxacin yet is more active than moxifloxacin during both the initial and continuation phases of treatment in a murine model. These results warrant further preclinical evaluation of DC-159a in selected drug combinations against drug-susceptible and fluoroquinolone-resistant tuberculosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aminopyridines / blood
Aminopyridines / pharmacokinetics
Aminopyridines / therapeutic use*
Animals
Antitubercular Agents / blood
Antitubercular Agents / pharmacokinetics
Antitubercular Agents / therapeutic use*
Female
Fluoroquinolones / blood
Fluoroquinolones / pharmacokinetics
Fluoroquinolones / therapeutic use*
Mice
Mice, Inbred BALB C
Tuberculosis / drug therapy*

Substances

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
Aminopyridines
Antitubercular Agents
Fluoroquinolones