In Vitro Activities of Terbinafine against Aspergillus Species in Comparison with Those of Itraconazole and Amphotericin B

Abstract

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...

Multilocus Phylogeny and Antifungal Susceptibility of Aspergillus Section Circumdati from Clinical Samples and Description of A. pseudosclerotiorum sp. nov

“…Similar results were obtained in our previous study on Aspergillus section Versicolores (46). TBF also has been reported to be highly effective in vitro against clinically relevant Aspergillus species, such as A. flavus, A. niger, A. nidulans, or A. terreus, and even against numerous isolates of A. fumigatus sensu stricto (47)(48)(49). To our knowledge, however, there is no previous information available on the activity of TBF against section Circumdati species.…”

Determination of Fungicidal Activities against Yeasts and Molds: Lessons Learned from Bactericidal Testing and the Need for Standardization

“…Again, most recent studies have used the NCCLS M38-A broth microdilution method and have been largely limited to Aspergillus spp. (21,25,29,50,60,(63)(64)(65)80). The fact that the inoculum recommended for determining the MICs of agents tested against Aspergillus spp., 1 ϫ 10 4 to 5 ϫ 10 4 CFU/ml, is higher than that for yeasts makes determination of a 3-log-unit decrease in CFU per milliliter from the final inoculum more feasible.…”

Synthesis, Biological Evaluation and 2D-QSAR Studies of Novel 6-Oxo-Pyridine-3-Carboxamide Derivatives as Antimicrobial and Antifungal Agents

“…Aspergillus fumigatusis largely responsible for increased the incidence of invasive aspergillosis (IA) in immunocompromised patients (Moore, Walls & Denning, 2001). Thus, the activity of the novel compounds were www.ccsenet.org/ijc International Journal of Chemistry Vol.…”