Compared with the in vitro activities of itraconazole (geometric mean MIC [GM], 0.56 g/ml) and amphotericin B (GM, 0.66 g/ml), the in vitro activity of terbinafine was inferior against Aspergillus fumigatus (GM, 19.03 g/ml) (P < 0.05) and superior against A. flavus (GM, 0.10 g/ml), A. terreus (GM, 0.16 g/ml), and A. niger (GM, 0.19 g/ml). Clinical correlation is required, as trailing endpoints are problematic.Aspergillus fumigatus remains the most common airborne fungal pathogen worldwide (8). Not surprisingly, the ubiquity of this organism coupled with the substantial increase in immunocompromised patients has resulted in a dramatic rise in the incidence of invasive aspergillosis over the last 2 decades. In a recent review of more than 1,000 autopsies in a university hospital, invasive aspergillosis was diagnosed as the cause of death in 4% of cases (17). Estimates of prevalence vary according to the underlying condition, ranging from 1% in patients with systemic lupus erythematosus to as high as 25 to 40% in patients with chronic granulomatous disease (4).Terbinafine (TERB) is an allylamine antifungal agent available in both topical and oral preparations. It is widely utilized in the treatment of dermatophyte infections. It is also reported to have good activity in vitro against Cryptococcus (12), some species of Candida (12), Penicillium marneffei (9), Aspergillus (5, 14-16), and other filamentous fungi (5). In vivo activity against Pneumocystis carinii has been described (2), and clinical activity against pulmonary aspergillosis has been reported (13).In this study, we determined the in vitro antifungal activities of TERB against six different species of Aspergillus, with a disproportionate number resistant to itraconazole (ITZ). We also examined the fungicidal activity of TERB. Furthermore, we directly compared both inhibitory and fungicidal results with those of ITZ and amphotericin B.A total of 100 clinical Aspergillus isolates comprising 60 A. fumigatus isolates, 13 isolates each of A. flavus and A. niger, 12 isolates of A. terreus, and 1 isolate each of A. nidulans and A. oryzae were used. Ten isolates were resistant to ITZ, 9 being A. fumigatus. Isolates for which the MICs of ITZ and amphotericin B were known were included to ensure quality control (3,6). All cultures were cultivated from frozen stock on Sabouraud dextrose agar (Oxoid, Basingstoke, United Kingdom) for 3 to 4 days at 30°C. TERB (Novartis Pharma, Basel, Switzerland) was provided as the standard hydrochloride salt, and ITZ (Janssen Pharmaceuticals, Beerse, Belgium) was provided in pure powder form. Both were supplied by their respective manufacturers. Amphotericin B with desoxycholate (AMB) was obtained from E. R. Squibb & Sons Limited, Middlesex, United Kingdom. Stock solutions (3,200 g/ml) of all drugs were prepared using appropriate solvents-TERB (dimethyl sulfoxide containing 5% Tween 80), ITZ (1:1 acetone and 0.2 M HCl), and AMB (sterile distilled water)-and adjusted for potency when necessary. Each stock was then dispensed into aliq...

The in vitro activity of BMS-207147 against 80 clinical isolates of Aspergillus was compared with that of itraconazole and amphotericin B, using a validated microtiter method. Geometric mean MICs (in g/ml) were as follows: 1.71 for BMS-207147, 0.67 for itraconazole, and 0.63 for amphotericin B. The range of concentrations of each drug was 0.125 to >16 g/ml. Aspergillus fumigatus was significantly more susceptible to BMS-207147 (P < 0.05) than A. terreus and A. flavus. No BMS-207147-resistant A. fumigatus isolates were identified, though eight itraconazole-resistant (MIC, >8 g/ml) isolates were. BMS-207147 is active against Aspergillus spp. at slightly high concentrations compared with itraconazole and amphotericin B.

Optimal methods for susceptibility testing of Candida spp. with flucytosine have not been determined. Breakpoints were recommended in 1984, but never validated. In this study, we compared the 1984 recommended macrodilution broth method (using an 80% endpoint) with a modification of the more recent NCCLS-recommended microdilution broth method with three endpointsspectrophotometric 50% and 80% and a no growth endpoint determined by eye. NCCLS and British Society for Medical Mycology (BSMM) breakpoints were also compared. One hundred and fifty isolates comprised of Candida albicans, Candida tropicalis, Candida krusei, Candida glabrata, Candida parapsilosis and Candida lusitaniae were tested. Reproducibility was excellent. For C. albicans (n = 65), the correlation between tests was excellent (>75%), with few major discrepancies (<5%). For C. tropicalis (n = 27), correlation was good (59%), but there were a small number of major discrepancies (up to 11%, depending on breakpoint used). Results by the broth macrodilution method were generally higher than both microdilution methods for C. glabrata (n = 16; correlation of 18.8%), but only one major discrepancy was seen. Ten of the 11 C. parapsilosis isolates tested were susceptible by all methods, regardless of breakpoint chosen, with a correlation of 18.2%, but no major discrepancies were seen. A correlation between all methods (50%) was seen with C. lusitaniae (n = 10), with many isolates resistant or intermediate. In contrast, correlation between methods for C. krusei was poor (<5%); NCCLS microtitre modification produced results that were classified as intermediate or resistant, regardless of the breakpoint used. The methodology for susceptibility testing C. albicans is robust. Additional work to optimize susceptibility testing with flucytosine is necessary for nonalbicans Candida species, especially C. krusei.