Abstract
BackgroundSporotrichosis is a chronic subcutaneous mycosis of humans and animals, which is typically acquired by traumatic inoculation of plant material contaminated with Sporothrix propagules, or via animals, mainly felines. Sporothrix infections notably occur in outbreaks, with large epidemics currently taking place in southeastern Brazil and northeastern China. Pathogenic species include Sporothrix brasiliensis, Sporothrix schenckii s. str., Sporothrix globosa, and Sporothrix luriei, which exhibit differing geographical distribution, virulence, and resistance to antifungals. The phylogenetically remote species Sporothrix mexicana also shows a mild pathogenic potential.MethodsWe assessed a genetically diverse panel of 68 strains. Susceptibility profiles of medically important Sporothrix species were evaluated by measuring the MICs and MFCs for amphotericin B (AMB), fluconazole (FLC), itraconazole (ITC), voriconazole (VRC), posaconazole (PCZ), flucytosine (5FC), and caspofungin (CAS). Haplotype networks were constructed to reveal interspecific divergences within clinical Sporothrix species to evaluate genetically deviant isolates.ResultsITC and PCZ were moderately effective against S. brasiliensis (MIC90 = 2 and 2 μg/mL, respectively) and S. schenckii (MIC90 = 4 and 2 μg/mL, respectively). PCZ also showed low MICs against the rare species S. mexicana. 5FC, CAS, and FLC showed no antifungal activity against any Sporothrix species. The minimum fungicidal concentration ranged from 2 to >16 μg/mL for AMB against S. brasiliensis and S. schenckii, while the MFC90 was >16 μg/mL for ITC, VRC, and PCZ.ConclusionSporothrix species in general showed high degrees of resistance against antifungals. Evaluating a genetically diverse panel of strains revealed evidence of multidrug resistant phenotypes, underlining the need for molecular identification of etiologic agents to predict therapeutic outcome.
Highlights
Sporotrichosis is a chronic subcutaneous mycosis of humans and animals, which is typically acquired by traumatic inoculation of plant material contaminated with Sporothrix propagules, or via animals, mainly felines
Using the methods recommended in the CLSI standard document M38-A2, we evaluated minimum inhibitory concentrations (MIC) for the following seven antifungal agents: amphotericin B (AMB), fluconazole (FLC), itraconazole (ITC), voriconazole (VRC), posaconazole (PCZ), flucytosine (5FC), and caspofungin (CAS)
The triazoles ITC and PCZ showed the best activity against S. brasiliensis strains, with MICs ranging from 0.25 to 4 μg/mL (Figure 2A) and from 0.5 to 2 μg/mL (Figure 2C), respectively
Summary
Sporotrichosis is a chronic subcutaneous mycosis of humans and animals, which is typically acquired by traumatic inoculation of plant material contaminated with Sporothrix propagules, or via animals, mainly felines. The Sporothrix genus, embedded in the plant-associated order Ophiostomatales, exhibits high genetic diversity [10,11], which is accompanied by a diversity of in vitro responses to the main antifungal agents [14] used in sporotrichosis treatment [7,15]. Such agents include potassium iodide [16] and itraconazole [17] for localized cutaneous and lymphocutaneous forms, and amphotericin B for disseminated cases [6,9,16]. Screening for antifungal susceptibilities during epidemiological surveillance programs could help to uncover putative multidrug resistant Sporothrix strains, and improve our ability to adjust therapeutic regimens and reduce relapse
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