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Antimicrobial Agents and Chemotherapy, September 1998, p. 2342-2346, Vol. 42, No. 9
Department of Microbiology and Immunology,
Received 9 April 1998/Returned for modification 5 May 1998/Accepted 29 June 1998
The candidacidal activity of nitric oxide (NO) as delivered by a
class of compounds termed diazeniumdiolates has been investigated. Diazeniumdiolates are stable agents capable of releasing NO in a
biologically usable form at a predicted rate, and three such compounds
were examined for activity. One compound,
(Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO), proved to be most suitable for examining NO activity due to
its relatively long half-life (20 h) and because of limited candidacidal activity of the uncomplexed DETA nucleophile. DETA-NO was
active against six species of Candida for which the MICs
necessary to inhibit 50% growth (MIC50s) ranged from 0.25 to 1.0 mg/ml. C. parapsilosis and C. krusei
were the most susceptible to the compound. In addition to a
determination of NO effects alone, the complex was utilized to
investigate the synergistic potential of released NO in combination
with ketoconazole, fluconazole, and miconazole. Activity was
investigated in vitro against representative strains of Candida
albicans, C. krusei, C. parapsilosis,
C. tropicalis, C. glabrata, and C. dubliniensis. Determination of MIC50,
MIC80 and MICs indicated that DETA-NO inhibits all strains
tested, with strains of C. parapsilosis and C. krusei being consistently the most sensitive. The combination of
DETA-NO with each azole was synergistic against all strains tested as
measured by fractional inhibitory concentration indices that ranged
from 0.1222 to 0.4583. The data suggest that DETA-NO or compounds with
similar properties may be useful in the development of new therapeutic
strategies for treatment of Candida infections.
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Synergy of Nitric Oxide and Azoles against
Candida Species In Vitro
*
Corresponding author. Mailing address: Department of
Microbiology and Immunology, Georgetown University, Washington, D.C. 20007. Phone: (202) 687-1802. Fax: (202) 687-1800. E-mail:
cihlarr{at}gunet.georgetown.edu.
Antimicrobial Agents and Chemotherapy, September 1998, p. 2342-2346, Vol. 42, No. 9
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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