Journal of Antimicrobial Chemotherapy, Vol 41, 59-65, Copyright © 1998 by The British Society for Antimicrobial Chemotherapy
F Barchiesi, LF Di Francesco, P Compagnucci, D Arzeni, A Giacometti and G Scalise
A chequerboard titration broth microdilution method, performed according to
the recommendations of the National Committee for Clinical Laboratory
Standards, was applied to study the in-vitro interaction of terbinafine
with amphotericin B, fluconazole and itraconazole against 30 strains of
Candida albicans isolated from the oral cavities of AIDS patients. MICs
were determined spectrophotometrically at 490 nm and read at either 24 h or
48 h. The end-point was defined as the drug concentration resulting in >
or = 90% inhibition of growth relative to control growth. Synergy, defined
as a fractional inhibitory concentration (FIC) index of < or = 0.50, was
observed in 93% (28 of 30) of terbinafine-amphotericin B interactions, in
47% (14 of 30) of terbinafine-fluconazole interactions and in 43% (13 of
30) of terbinafine-itraconazole interactions; antagonism (FIC > 2.0) was
not observed. Where synergy was not achieved, there was still a decrease,
although not as dramatic, in the MIC of one or both drugs when used in
combination. Reading the MICs on day 2 did not significantly affect the
mode of interaction of terbinafine-triazoles, while for terbinafine-
amphotericin B the proportion of synergic interactions dropped from 93% (28
of 30) to 30% (nine of 30; P = 0.0001). Antagonism was not observed for any
drug combination even at 48 h. Minimum fungicidal concentrations (MFCs) of
all drugs alone and in combination were determined against five isolates.
Neither terbinafine nor the two triazoles showed fungicidal activity when
tested alone or in combination. The fungicidal activity of amphotericin B
was slightly enhanced when combined with terbinafine, there being a
decrease of two- fold dilutions in the amphotericin B MFCs against all five
isolates tested. Thus terbinafine enhances the activities of amphotericin B
and triazoles against C. albicans in vitro. Clearly, clinical studies are
warranted to elucidate further the potential utility of these combination
therapies.
ORIGINAL ARTICLES
In-vitro interaction of terbinafine with amphotericin B, fluconazole and itraconazole against clinical isolates of Candida albicans
Institute of Infectious Diseases & Public Health, University of Ancona, Italy.
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