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Antimicrobial Agents and Chemotherapy, May 2005, p. 2008-2014, Vol. 49, No. 5
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.5.2008-2014.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Lethality of Quinolones against Mycobacterium smegmatis in the Presence or Absence of Chloramphenicol

Public Health Research Institute, 225 Warren Street, Newark, New Jersey 07103,¹ Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, Michigan 48105,² Division of Medicinal and Natural Products Chemistry, The University of Iowa, Iowa City, Iowa 52242³

Received 5 October 2004/ Returned for modification 29 November 2004/ Accepted 11 January 2005

Quinolones were examined for rapid lethal activity against Mycobacterium smegmatis in the presence and absence of chloramphenicol, an inhibitor of protein synthesis. C-8 methoxy, C-6 fluorine, and particular C-7 ring substituents enhanced rapid killing. With the surprising exception of moxifloxacin, higher quinolone concentrations were required for lethal activity in the presence of chloramphenicol than in its absence. Moxifloxacin was also unusual in lacking the time lag characteristic of fluoroquinolone lethality. Several fluoroquinolone dimers, which represent quinolones with large C-7 substituents, showed modest bacteriostatic activity. Unlike other quinolones, the dimers failed to display lethal activity. The insensitivity of moxifloxacin to chloramphenicol has not been observed with other bacteria and may therefore reflect unique aspects of mycobacterial gyrase.

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