IN-VITRO INTERACTION OF TERBINAFINE WITH AMPHOTERICIN-B, FLUCONAZOLE AND ITRACONAZOLE AGAINST CLINICAL ISOLATES OF CANDIDA-ALBICANS

A chequerboard titration broth microdilution method, performed accordi ng to the recommendations of the National Committee for Clinical Labor atory Standards, was applied to study the in-vitro interaction of terb inafine with amphotericin B, fluconazole and itraconazole against 30 s trains of Candida albicans isolated from the oral cavities of AIDS pat ients, MICs were determined spectrophotometrically at 490 nm and read at either 24 h or 48 h, The endpoint was defined as the drug concentra tion resulting in greater than or equal to 90% inhibition of growth re lative to control growth. Synergy, defined as a fractional inhibitory concentration (FIC) index of less than or equal to 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 decre ase, although not as dramatic, in the MIC of one or both drugs when us ed in combination. Reading the MICs on day 2 did not significantly aff ect the mode of interaction of terbinafine-triazoles, while for terbin afine-amphotericin B the proportion of synergic interactions dropped f rom 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 co ncentrations (MFCs) of all drugs alone and in combination were determi ned against five isolates, Neither terbinafine nor the two triazoles s howed fungicidal activity when tested alone or in combination, The fun gicidal 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 terbinafin e enhances the activities of amphotericin B and triazoles against C. a lbicans in vitro, Clearly, clinical studies are warranted to elucidate further the potential utility of these combination therapies.