Control
Treatment of feline sporotrichosis is a major challenge to public health because the number of oral antifungal agents is limited; these have numerous adverse effects and high cost (Rodrigues et al.
2016c). The drug choice should take into account the clinical condition of the patient, the extent of the skin lesions, the drug interactions, the adverse effects, and the systemic involvement (Orofino-Costa et al. 2015, 2017). The treatment of feline sporotrichosis includes local hyperthermia, potassium iodide, azoles (ketoconazole and itraconazole), amphotericin B, and the allylamine terbinafine. Currently, itraconazole and potassium iodide are the most used drugs in the treatment of feline sporotrichosis (Pereira et al. 2010; Reis et al. 2012; Gremiao et al. 2015, 2017), and clinical cure is observed regardless of the initial clinical conditions or coinfection with FIV and/or FeLV. The treatment of feline sporotrichosis may last several weeks to several months (average time 4-9 months) and must be continued for at least 1 month after clinical cure. Recently, the combination of itraconazole and potassium iodide was successfully reported as a new therapeutic option (itraconazole 100 mg/day and KI 2.5-20 mg/kg/day), with a high cure rate (96.15%) and 14 weeks of treatment on average (Reis et al. 2016). Recurrence may occur, demonstrating the possibility of lesion reactivation, despite the completion of treatment (Pereira et al. 2010; Gremiao et al. 2011, 2015; Chaves et al. 2013).Sporothrix brasiliensis is the main etiological agent of feline sporotrichosis in Brazil, and little variation exists in the susceptibility profile to azoles in this species (Rodrigues et al. 2014c; Espinel-Ingroff et al. 2017). Significant activity of itraconazole (minimum inhibitory concentration (MIC), 0.125-2 μg∕mL), amphotericin B (MIC, 0.125-4 μg∕mL), and ketoconazole (0.0312-2 μg∕mL) against S.
brasiliensis in feline sporotrichosis has been reported (Brilhante et al. 2016). Fluconazole, caspofungin, and 5-fluorocytosine have no antifungal in vitro activity against S. brasiliensis or other species of the clinical clade (Rodrigues et al. 2014c; Marimon et al. 2008b). Significant differences exist between the minimum concentrations necessary to inhibit the growth of Sporothrix in vitro and the concentration necessary to reduce the number of colony-forming units, demonstrating the fungistatic effect of most commercially available antifungals (Rodrigues et al. 2014c). It is important to note that isolates of S. brasiliensis recovered recently (2011-2012) from humans during the epidemic in Rio de Janeiro were less susceptible to amphotericin B, itraconazole, posaconazole, voriconazole, and terbinafine compared to isolates collected before 2004 (1998-2004), suggesting that this epidemiological profile might be changing over time (Borba-Santos et al. 2015). In this scenario, terbinafine may be a promising alternative against the mycelium and yeast forms of S. brasiliensis, followed by posaconazole (Borba-Santos et al. 2015).In the last decades, human sporotrichosis has been treated with itraconazole, the drug of choice for cutaneous and lymphocutaneous forms of the mycosis in humans due to its good tolerability and lower incidence of adverse effects (Kauffman et al. 2007). This drug is also used in immunocompromised patients with clinical forms with systemic involvement (Bolao et al. 1994). However, for some researchers, the drug of choice is potassium iodide (de Macedo et al. 2015a, b; Costa et al. 2013), which provides an effective and affordable treatment. The treatment with antifungal drugs can take from weeks to months to restore a favorable clinical profile and is continued for at least 1 month after the complete disappearance of symptoms (Bonifaz and Vazquez-Gonzalez 2013). The prognosis of sporotrichosis varies from good to regular even in immunocompromised patients, although relapse may occur (Kauffman et al.
2007).The drug of choice for the treatment of fixed cutaneous and lymphocutaneous sporotrichosis is 200 mg itraconazole, orally for 3-6 months (Kauffman et al. 2007). This drug belongs to the azole class and acts by inhibiting the ergosterol biosynthesis pathway, the primary sterol of fungal membranes. As ergosterol is depleted, it is replaced by unusual sterols, changing the normal permeability and fluidity of the membrane and, consequently, the binding of enzymes to the membrane such as those involved in cell wall synthesis. Other drugs of the same class are used, such as fluconazole, which are less effective than itraconazole but are recommended to patients who do not tolerate or use drugs that interact with itraconazole (Kauffman et al. 2007).
Amphotericin B binds to ergosterol and disturbs the normal functioning of the membrane, causing leakage of the intracellular content. One of the problems associated with this drug is its toxicity to mammalian cells, particularly nephrotoxicity. The treatment of choice when patients have severe sporotrichosis or are at risk of death is amphotericin B (Kauffman et al. 2007; Silva-Vergara et al. 2012).
In developing countries, the first-choice drug is potassium iodide because it is more economically viable. The mechanism of action of potassium iodide is unknown; whether it acts against the fungus via a fungicidal mechanism or by increasing the body's defense mechanism through the immune response is not known (Rex and Bennett 1990; Sterling and Heymann 2000).
Alternatively, thermotherapy has been used for treatment of sporotrichosis, with the advantage of being low cost and having no side effects. The temperature of the human body is higher than the optimum temperature for fungal growth, and thus, the fungus does not grow well at 37 °C. Judging from this information, the growth of a Sporothrix isolate was assessed under different temperatures. This study showed that temperatures higher than 39 °C inhibit fungal growth (Mackinnon and Conti-Diaz 1963). Indeed, reports exist of successful treatment of human sporotrichosis using thermotherapy (Hiruma et al. 1987). Thermotherapy has also been successfully used in an infected cat (Honse et al. 2010).
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