Is terbinafine an effective treatment for feline sporotrichosis?

BACKGROUND: Terbinafine has been successfully used in the treatment of human sporotrichosis; however, its effectiveness in the treatment of feline sporotrichosis is unknown. Therefore, this study aimed to describe the use of terbinafine in the treatment of feline sporotrichosis. METHODS: A cohort study was conducted in cats with sporotrichosis to assess the effectiveness and safety of terbinafine (30‒60 mg/kg/day). Clinical examination and analysis of laboratory parameters were performed monthly until clinical signs resolved or terbinafine treatment was discontinued. RESULTS: Of the 54 cats with sporotrichosis included in the study, 19 were lost during follow-up and five were withdrawn from the study due to switching to treatment with another prescription drug. Of the remaining 30 cats, 10 achieved clinical cure, with a median treatment time of 18.5 weeks. Treatment failed in 18 cases, and two cats died. Twenty-two cats had adverse reactions to terbinafine treatment, and 10 cats showed elevation of serum transaminases. LIMITATION: Loss during follow-up was high, which makes it difficult to draw accurate conclusions regarding clinical outcomes. CONCLUSION: The low rate of clinical cure observed suggests that terbinafine does not represent an effective treatment option for cases of feline sporotrichosis.

Plasma itraconazole concentrations during treatment of feline sporotrichosis.

Itraconazole (ITZ) is the most used drug to treat feline sporotrichosis; however, little is known about its pharmacokinetics in cats with this mycosis. The aim of this study was to determine plasma ITZ concentrations in cats with sporotrichosis treated with ITZ as monotherapy or in combination with potassium iodide (KI). Cats diagnosed with sporotrichosis received orally ITZ (100 mg/cat/day) or combination therapy with ITZ (100 mg/cat/day) and KI (2.5-5 mg/kg/day) in the case of worsening or stagnation of the clinical condition. At each monthly visit, blood samples were collected at an interval of 4 h for analysis of trough and peak plasma ITZ concentrations by HPLC. Clinical features and laboratory parameters were evaluated during follow-up. Sixteen cats were included in the study. The median plasma ITZ concentration of all cats was 0.75 µg/mL. The median plasma ITZ concentration was 0.5 µg/mL in cats that received ITZ monotherapy (n = 12) and 1.0 µg/mL in those treated with ITZ + KI (n = 4). The clinical cure rate was 56.3% (n = 9) and the median treatment duration was 8 weeks. Nine cats (56.3%) developed adverse clinical reactions, and hyporexia was the most frequent (n = 8; 88.9%). Serum alanine aminotransferase was elevated in four cats (25%). The median plasma ITZ concentration detected in cats was considered to be therapeutic (>0.5 µg/mL) and was reached after 4 weeks of treatment. Plasma ITZ concentrations were higher in cats that received ITZ + KI compared to those treated only with ITZ, suggesting pharmacokinetic synergism between these drugs.

Itraconazole is the most common therapy for feline sporotrichosis, and combination therapy with potassium iodide is used in nonresponsive cases. Our study showed that all cats achieved a therapeutic plasma concentration of itraconazole, with higher levels in cats treated with the combination therapy.

Combination therapy of itraconazole and an acylhydrazone derivative (D13) for the treatment of sporotrichosis in cats.

Acylhydrazone (AH) derivatives represent a novel category of anti-fungal medications that exhibit potent activity against Sporothrix sp., both in vitro and in a murine model of sporotrichosis. In this study, we demonstrated the anti-fungal efficacy of the AH derivative D13 [4-bromo-N'-(3,5-dibromo-2-hydroxybenzylidene)-benzohydrazide] against both planktonic cells and biofilms formed by Sporothrix brasiliensis. In a clinical study, the effect of D13 was then tested in combination with itraconazole (ITC), with or without potassium iodide, in 10 cats with sporotrichosis refractory to the treatment of standard of care with ITC. Improvement or total clinical cure was achieved in five cases after 12 weeks of treatment. Minimal abnormal laboratory findings, e.g., elevation of alanine aminotransferase, were observed in four cats during the combination treatment and returned to normal level within a week after the treatment was ended. Although highly encouraging, a larger and randomized controlled study is required to evaluate the effectiveness and the safety of this new and exciting drug combination using ITC and D13 for the treatment of feline sporotrichosis. IMPORTANCE: This paper reports the first veterinary clinical study of an acylhydrazone anti-fungal (D13) combined with itraconazole against a dimorphic fungal infection, sporotrichosis, which is highly endemic in South America in animals and humans. Overall, the results show that the combination treatment was efficacious in ~50% of the infected animals. In addition, D13 was well tolerated during the course of the study. Thus, these results warrant the continuation of the research and development of this new class of anti-fungals.

A Randomized Clinical Trial Comparing Itraconazole and a Combination Therapy with Itraconazole and Potassium Iodide for the Treatment of Feline Sporotrichosis.

Feline sporotrichosis is an endemic disease with high occurrence in Brazil. Itraconazole (ITZ) remains the drug of choice for treating this disease in cats, despite the increasing reports of therapeutic failure. A controlled, randomized clinical trial was performed on 166 naive cats with sporotrichosis to assess the effectiveness and safety of the combination therapy with ITZ and potassium iodide (KI) compared with ITZ monotherapy. Cats were randomly allocated into two treatment groups: G1-ITZ 100 mg/cat/day-and G2-ITZ 100 mg/cat/day + KI 2.5-20 mg/kg/day. Cats treated in G2 presented 77% more risk of reaching a clinical cure (a positive effect) than those treated in G1, even when controlled by negative predictors. The survival curves of the two treatment protocols indicate that a clinical cure was achieved faster in G2. An increase in the KI dose was necessary in 28 cats due to the persistence of clinical signs. Adverse reactions were equally frequent in both groups and manageable with a temporary drug suspension and/or a hepatoprotective therapy. The combination therapy was associated with a higher cure rate and a shorter treatment time, suggesting that ITZ+KI arises as a better option for treating feline sporotrichosis and should be considered the first-line treatment, especially in the presence of negative predictors.

Advances and challenges in the management of feline sporotrichosis.

The domestic cat is the most susceptible host to Sporothrix infection, developing severe clinical forms. Few effective antifungal agents are available for treating feline sporotrichosis, and cases of treatment failure are common. Treatment success depends on cat health status, therapy-related factors, as well as social/economic issues, but it is mainly contingent upon the host-fungus interaction. The owner's adherence is critical and should be reinforced throughout the treatment to increase the chances of a successful outcome. The antifungal agents described for feline sporotrichosis are most often used in monotherapy regimens. Due to cases in which the treatment with itraconazole failed, the use of antifungal agents in combination should be considered to achieve synergy. The combination of itraconazole and potassium iodide represents an important option for the treatment of naïve cats presenting multiple cutaneous lesions, nasal mucosal lesions and/or respiratory signs, as well as for refractory cases. However, the therapeutic options for unsuccessfully treated cases are scarce. Therefore new options are needed, even more taking into account that there are many in vitro potential molecules not available for use in cats yet. More studies are necessary to correlate in vitro antifungal susceptibility tests results and the outcome of cats treated due to sporotrichosis. This review will briefly discuss both the antifungal drugs and treatment protocols used in cats with sporotrichosis, as well as the determinants of treatment failure.

Sodium iodide: an alternative treatment option for feline sporotrichosis? / Iodeto de sódio: uma alternativa de tratamento para a esporotricose felina?

Background: Sporotrichosis is caused by pathogenic fungi of the genus Sporothrix. The clinically relevant species are S. schenckii, S. globosa and S. brasiliensis. In Brazil, S. brasiliensis is the most prevalent etiological agent among humans and cats. In cats with sporotrichosis, skin lesions are mainly characterized by nodules and ulcers, usually located in the head, nasal region and limbs. The presence of respiratory signs concomitantly with cutaneous lesions is frequent, especially sneezing, and may be associated with lesions located in the nasal mucosa. Ketoconazole (KTZ), itraconazole (ITZ), potassium iodide (KI), sodium iodide (NaI), terbinafine (TRB), fluconazole (FLZ) and amphotericin B (AMB) are the drugs currently available for treating feline sporotrichosis. ITZ remains the drug of choice. ITZ combined with KI has been successfully used in the treatment of naïve cats (especially cases with lesions in the nasal region), cases of recurrence and refractory to ITZ. Clinical cure with NaI has been described in some cases, but its use has been limited by adverse reactions. The conventional formulation is the saturated solution and the recommended dose in the treatment of feline sporotrichosis is 10 mg/kg every 12 h. Cats are sensitive to iodide preparations and should be carefully monitored for clinical evidence of iodism, such as apathy, anorexia, vomiting, diarrhea, hypothermia, hyperthermia, cardiomyopathy, hyperexcitability, muscular spasms and ptyalism. The purpose of this study was to evaluate the therapeutic response of NaI capsules in feline sporotrichosis.Materials, Methods & Results: An observational cohort study was conducted in cats with sporotrichosis at the Laboratory of Clinical Research in Dermatozoonoses in Domestic Animals (Lapclin-Dermzoo), Evandro Chagas National Institute of Infectious Diseases (INI)/Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil.[...](AU)

Sodium iodide: an alternative treatment option for feline sporotrichosis? / Iodeto de sódio: uma alternativa de tratamento para a esporotricose felina?

Background: Sporotrichosis is caused by pathogenic fungi of the genus Sporothrix. The clinically relevant species are S. schenckii, S. globosa and S. brasiliensis. In Brazil, S. brasiliensis is the most prevalent etiological agent among humans and cats. In cats with sporotrichosis, skin lesions are mainly characterized by nodules and ulcers, usually located in the head, nasal region and limbs. The presence of respiratory signs concomitantly with cutaneous lesions is frequent, especially sneezing, and may be associated with lesions located in the nasal mucosa. Ketoconazole (KTZ), itraconazole (ITZ), potassium iodide (KI), sodium iodide (NaI), terbinafine (TRB), fluconazole (FLZ) and amphotericin B (AMB) are the drugs currently available for treating feline sporotrichosis. ITZ remains the drug of choice. ITZ combined with KI has been successfully used in the treatment of naïve cats (especially cases with lesions in the nasal region), cases of recurrence and refractory to ITZ. Clinical cure with NaI has been described in some cases, but its use has been limited by adverse reactions. The conventional formulation is the saturated solution and the recommended dose in the treatment of feline sporotrichosis is 10 mg/kg every 12 h. Cats are sensitive to iodide preparations and should be carefully monitored for clinical evidence of iodism, such as apathy, anorexia, vomiting, diarrhea, hypothermia, hyperthermia, cardiomyopathy, hyperexcitability, muscular spasms and ptyalism. The purpose of this study was to evaluate the therapeutic response of NaI capsules in feline sporotrichosis.Materials, Methods & Results: An observational cohort study was conducted in cats with sporotrichosis at the Laboratory of Clinical Research in Dermatozoonoses in Domestic Animals (Lapclin-Dermzoo), Evandro Chagas National Institute of Infectious Diseases (INI)/Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil.[...]