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JAC Advance Access published online on November 22, 2005
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dki418
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© The Author 2005. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Received June 13, 2005
Revised October 18, 2005
Accepted October 21, 2005

Original article

Antimicrobial activity of picolinic acid against extracellular and intracellular Mycobacterium avium complex and its combined activity with clarithromycin, rifampicin and fluoroquinolones

Shanshan Cai 1, Katsumasa Sato 1, Toshiaki Shimizu 1, Seiko Yamabe 1, Miho Hiraki 1, Chiaki Sano 1, and Haruaki Tomioka 1 *

1 Department of Microbiology and Immunology, Shimane University School of Medicine, Izumo, Shimane 693-8501, Japan

* To whom correspondence should be addressed.
Haruaki Tomioka, E-mail: tomioka{at}med.shimane-u.ac.jp


  Abstract

Objectives: A natural metal ion chelator, picolinic acid (PA), is known to potentiate macrophage antimycobacterial activity. Here, we studied the antimicrobial activity of PA against extracellular and intramacrophage Mycobacterium avium complex (MAC) organisms.

Methods: MAC organisms, MAC-infected macrophages or MAC-infected type II pneumocytes were cultured in the presence or absence of PA with or without antimycobacterial drugs, and residual bacterial cfu of extracellular or intracellular MAC were counted on 7H11 agar plates.

Results: First, PA exhibited antimicrobial activity against extracellular and intramacrophage MAC. The effect of PA was mimicked by other metal ion-chelating agents, such as ethylenediamine tetraacetic acid and O, O'-bis (2-aminophenyl) ethyleneglycol-N, N, N', N'-tetraacetic acid. Second, PA potentiated antimicrobial effects of a two-drug combination of clarithromycin/rifampicin and some fluoroquinolones (levofloxacin, sitafloxacin and gatifloxacin) against extracellular and intramacrophage MAC. Similar combined effects of PA with clarithromycin/rifampicin were also seen in the case of MAC residing within type II alveolar epithelial cells.

Conclusions: PA exerted an appreciable anti-MAC activity, when used singly or in combination with some antimycobacterial drugs (clarithromycin/rifampicin and fluoroquinolones), suggesting the usefulness of PA as an adjunct for clinical antimicrobial chemotherapy of MAC infections.

Keywords: macrophages; chelating agents; immunoadjunctive therapy; immunomodulators.
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T. Shimizu and H. Tomioka
Activity of Picolinic Acid in Combination with the Antiprotozoal Drug Quinacrine against Mycobacterium avium Complex.
Antimicrob. Agents Chemother., September 1, 2006; 50(9): 3186 - 3188.
[Abstract] [Full Text] [PDF]


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