In Vitro Susceptibilities of Isolates of Sporothrix schenckii to Itraconazole and Terbinafine

Abstract

Thirty isolates of the yeast form of Sporothrix schenckii were evaluated for in vitro susceptibility to itraconazole and terbinafine by the recommended NCCLS modified technique (M27-A2). The MICs of itraconazole obtained oscillated between 0.062 and 4.0 g/ml, and those of terbinafine oscillated between 0.007 and 0.50 g/ml; therefore, terbinafine showed greater in vitro activity.Sporotrichosis is a subacute or chronic infection affecting both animals and humans and is characterized by nodular cutaneous and subcutaneous lesions, which may involve the adjacent lymphatic system, which suppurates and drains (1,20).Itraconazole is currently considered the treatment of choice to treat the diverse clinical manifestations of sporotrichosis (13,14,17,18). On the other hand terbinafine by virtue of its excellent in vitro and in vivo activity is under comparative evaluation for its therapeutic potential for a wide range of fungal infections (4,6,8,11,21,22).Promising in vitro results with terbinafine for both the fixed and the lymphocutaneous forms of sporotrichosis due to the fungus Sporothrix schenckii (10,11,21) are being compared and confirmed clinically (4,8,10,19).In this study, our objective was to determine the in vitro efficacy of terbinafine against isolates of Sporothrix schenckii by the technique of macrodilution in a liquid medium (NCCLS M27-A2) (15) adapted for dimorphic fungi.Thirty strains of Sporothrix schenckii, including 2 reference isolates (ATCC 201679 and M527-88), 18 human clinical isolates, and 10 animal isolates (9 from cats and 1 from a horse) were included in this study. All the samples were isolated from clinical specimens, identified by micromorphological characteristics and demonstration of typical dimorphism. They were maintained in brain heart infusion (BHI) solid medium-0.5% glucose at a controlled temperature of 4°C, with replication onto new medium at 6-month intervals, and converted to the yeast form through successive passages in BHI solid medium and incubation at 35°C. Quality control (QC) strains Candida krusei (ATCC 6258) and Candida parapsilosis (ATCC 22019) were tested in parallel and were inhibited by MICs at the correct range for the antifungal tested (itraconazole) (15). The MIC range of terbinafine for the QC Candida strains has not yet been established by the NCCLS.Susceptibility tests were conducted using a technique of macrodilution in a liquid medium in accordance with the NCCLS protocol (M27-A2) (15), adapted for dimorphic fungi to include a 5-day incubation period to compensate for the sluggish growth of the yeast phase of Sporothrix schenckii, which requires 5 days to reach exponential growth (3, 7) and the addition of glucose to the medium (20 g/liter). The inoculum was prepared spectrophotometrically (520 nm, 60% of transmittance) to reach approximately 1 ϫ 10 6 to 5 ϫ 10 6 CFU/ml, at an incubation temperature of 35°C.The drugs itraconazole (Janssen Pharmaceutical, Beerse, Belgium) and terbinafine (Novartis Research Institute, Vienna, Austria) were obtained in their pur...

Antifungal Susceptibilities of Sporothrix albicans, S. brasiliensis, and S. luriei of the S. schenckii Complex Identified in Brazil

“…S. schenckii has been reported to show a high MIC to itraconazole by several authors (6,7,10). Although breakpoints have not been established for S. schenckii, document M38-A3 (2) suggests that, for analytical purposes, a MIC of Ն4.0 g/ml for itraconazole may be considered resistant for some filamentous fungi.…”

A 6-Year-Old Boy with a Nodule on His Hand

“…The same clinical features were seen in our case. [1][2][3] Sometimes, the culture may be negative and biopsy is nonspecific; 4 however, in our patient, both tests confirmed a diagnosis of sporotrichosis. Potassium iodide is extremely effective in localized forms and should be continued for 3 to 4 weeks after clinical cure.…”

“…Itraconazole at 100 mg to 200 mg per day is effective in both cutaneous and systemic cases. [4][5][6] …”

Suscetibilidade in vitro de isolados de Sporothrix schenckii frente à terbinafina e itraconazol

“…Outros estudos confirmaram a boa atividade in vitro do fármaco frente ao S. schenckii, sendo considerado o tratamento de eleição para as formas cutânea e cutânea-linfática da micose em humanos 4 10 11 . Porém, têm sido demonstrados casos de resistência in vitro ao fármaco, resultando em CIMs de 4µg/ml para isolados de felinos com a forma sistêmica da micose 12 .…”