In Vitro Susceptibility of Sporothrix schenckii to Six Antifungal Agents Determined Using Three Different Methods

Abstract

The in vitro susceptibility of Sporothrix schenckii to antifungal drugs has been determined with three different methods. Nineteen Peruvian clinical isolates of S. schenckii were tested against amphotericin B (AB), flucytosine (FC), fluconazole (FZ), itraconazole (IZ), voriconazole (VZ), and ketoconazole (KZ). Modified NCCLS M38-A, Sensititre YeastOne (SYO), and ATB Fungus 2 (ATBF2) methods were used to determine the MICs. ATCC isolates of Candida parapsilosis, Candida krusei, and Aspergillus flavus were used for quality control. Sporothrix inocula were prepared with the mycelial form growing on potato dextrose agar at 28 ؎ 2°C. MICs of AB, FC, FZ, and IZ were determined with all three methods, VZ with M38-A and SYO, and KZ with only SYO. The three methods showed high MICs of FZ and FC (MIC 90 of 0.5 g/ml), being homogeneously lower than those of IZ and KZ. The M38-A method showed a variable MIC range of VZ (4.0 to 16 g/ml); the geometric mean (GM) was 9.3 g/ml. The MIC range of AB was wide (0.06 to 16 g/ml), but the GM was 1.2 g/ml, suggesting that the MIC is strain dependent. Agreement (two log 2 dilutions) between commercial techniques and the modified M38-A method was very high with FZ, IZ, and FC. In AB and VZ, the agreement was lower, being related to the antifungal concentrations of each method. The highest activity against S. schenckii was found with IZ and KZ. Lack of activity was observed with FZ, VZ, and FC. When AB is indicated for sporotrichosis, the susceptibility of the strain must be analyzed. Commercial quantitative antifungal methods have a limited usefulness in S. schenckii. Sporotrichosis is a subacute or chronic infection that affects humans and other mammals and is produced by the dimorphic fungus Sporothrix schenckii.The infection is acquired when the fungus penetrates through the skin due to trauma, at times minimal, or more rarely through the respiratory tract, causing pulmonary infection (20). The most frequent manifestation of sporotrichosis is the cutaneous-lymphatic form followed by fixed cutaneous infection. In patients with severe underlying disease and the immunodepressed, the disease can spread and cause death (5). The standard treatment of cutaneous-lymphatic sporotrichosis is potassium iodine, with which complete remission of lesions can be achieved in 2 to 3 months (11). Despite the development of new antifungal drugs, potassium iodine continues to be a commonly used therapy probably because of its wide availability. However, the use of potassium iodine may be associated with mild adverse effects, such as gastric intolerance, or more serious adverse events, such as vasculitis, periarthritis, and hypothyroidism, among others (23). Orally administered itraconazole (IZ) has been shown to be effective in the treatment of cutaneous-lymphatic and systemic sporotrichosis (1, 24), whereas visceral and disseminated forms have classically been treated with amphotericin B (AB), with various results (12,22).Studies on the susceptibility of S. schenckii to commonly used antifungals have ra...

Sporothrix schenckii associated with armadillo hunting in Southern Brazil: epidemiological and antifungal susceptibility profiles

“…Our studies complement this work and further suggest that the ecological imbalance also impacts the epidemiology of sporotrichosis, which is the most common subcutaneous mycosis in Brazil. Regarding susceptibility, the MICs classified the isolates as susceptible to itraconazole, ketoconazole and terbinafine, with similar results reported by Alvarado-Ramirez & Torres-Rodrigues 16 and Marimon et al 17 . Specific studies focusing on the susceptibility of S. schenckii isolated from lesions caused by armadillos were not found, but the tests herein did not show antifungal resistance and were in agreement with the evolution of patient treatment.…”

Sporothrix schenckii and Sporotrichosis

“…MIC values for itraconazole and voriconazole determined by Etest were significantly lower than those obtained by microdilution (87). The Sensititre YeastOne and ATB Fungus 2 methods compared with CLSI M38-A2 show high agreement with microdilution for fluconazole, itraconazole, and 5-fluorocytosine, but for amphotericin B and voriconazole, agreement is lower (9).…”

“…Although some strains can show resistance to this drug, geometric means commonly are low, ranging from 0.4 g/ml (9) to 4.08 g/ml (257). In general, despite the use of fluconazole as a therapeutic agent in some human and veterinary sporotrichosis cases (31,50), this antifungal does not inhibit S. schenckii growth in vitro (9,63,90,152,172,257). Some S. schenckii strains are susceptible to voriconazole in vitro, since MIC values of as low as 0.12 g/ml have been found (107); however, the high geometric mean MIC values, ranging from 6.50 g/ml (155) to 13.2 g/ml (152), suggest that most isolates are resistant in vitro to this drug.…”

“…Posaconazole is a broadspectrum triazole, but its use in clinical sporotrichosis is yet to be evaluated (214,235). Susceptibility testing with voriconazole, ravuconazole, micafungin, and other new antifungal agents is still incipient, and so far there is no indication for use of these drugs for the treatment of sporotrichosis (9,169,178,233). There are studies showing different results for the same antifungal agent according to geographic area, the species of Sporothrix, and the method used (9,88,169).…”

Subcutaneous antifungal screening of Latin American plant extracts againstSporothrix schenckiiandFonsecaea pedrosoi

“…It occurs globally in tropical and subtropical regions and is characterized by nodular lesions, associated with lymphadenopathy ( Morris-Jones, 2002;Ramos-e-Silva et al, 2007), which become disseminated in AIDS patients (Ware et al, 1999). The available therapy in the majority of patients consists of treatment with terbinafine (Hull & Vismer, 1992), potassium iodide (Sandhu & Gupta, 2003), amphotericin B (Kohler et al, 2007), itraconazole and ketoconazole (Alvarado-Ramírez & Torres-Rodríguez, 2007).…”