Sodium Iodide: an Alternative Treatment Option for Feline Sporotrichosis?

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. Twenty-eight cats with sporotrichosis confirmed by isolation of Sporothrix spp. in culture, no previous systemic antifungal therapy, and weight above 3.0 kg, were included in the study. The treatment consisted of NaI oral capsules (5 mg/kg/once daily). In cats without clinical improvement after one month of treatment, the dose was increased (10 mg/kg/once daily). The cats were followed up monthly by clinical examination, complete blood count and biochemical analysis (urea, creatinine, alanine aminotransferase - ALT, aspartate aminotransferase - AST, alkaline phosphatase - FA). All procedures were approved by the Animal Ethics Committee (CEUA/Fiocruz), number LW 56/13, and the informed consent term was obtained from all tutors. Clinical cure was achieved in six (21.4%) cases and treatment failure was observed in 13 (46.4%) animals. Seven (25%) cats were lost during follow up, and unknown causes of death occurred in two cases (7.1%). Ten animals (35.7%) presented clinical adverse reactions at some point during treatment. Hyporexia and weight loss were the most frequent ones. Three cats presented alteration in renal function.Discussion: Treatment of feline sporotrichosis in epizootic areas has been a challenge for veterinarians and tutors. Additionally, there are few studies evaluating treatment regimens for this mycosis in animals. In this study, NaI was compounded in capsules, because it is easier to administer when compared to the solution, as previously described for KI. Despite the low cost and the convenient administration of the capsule, NaI presented a low cure rate with the dose used. The study of new pharmaceutical forms and lower doses of low-cost drugs is necessary in a scenario of epizootic sporotrichosis, where investments for the development of new antifungal agents are scarce

Avaliação da resposta terapêutica ao iodeto de sódio em cápsulas na esporotricose felina

Made available in DSpace on 2018-01-30T15:42:14Z (GMT). No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) beatriz_carvalho_ini_mest_2016.pdf: 1217430 bytes, checksum: 0edcf35b52b64a46cabc8dac5ae61a89 (MD5)Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Esporotricose é uma micose de implantação, causada por espécies do complexo Sporothrix, que infectam o ser humano e diferentes espécies animais, principalmente os gatos. O tratamento de gatos com esporotricose é difícil em decorrência de vários fatores, dentre eles, opções terapêuticas limitadas, ocorrência de falhas terapêuticas, além do custo elevado. Recentemente, a utilização de iodeto de potássio em uma forma farmacêutica não convencional (cápsula) e dose inferior a da literatura permitiu a obtenção de resultados satisfatórios. Em relação ao iodeto de sódio, poucos estudos descreveram a sua utilização e a efetividade do fármaco em cápsulas não foi relatada. Portanto, a necessidade de ampliação das opções terapêuticas, além da possibilidade de redução dos efeitos adversos com a utilização de uma dose inferior à preconizada, motivaram a elaboração deste estudo, o qual teve como objetivo avaliar a resposta terapêutica ao iodeto de sódio em gatos com esporotricose. Foi realizado um estudo de coorte observacional, no qual a população foi constituída por gatos com diagnóstico de esporotricose confirmado pelo isolamento de Sporothrix spp., acompanhados no Instituto Nacional de Infectologia Evandro Chagas/Fundação Oswaldo Cruz, no período de setembro 2014 a janeiro de 2016. O tratamento consistiu na administração de cápsulas de iodeto de sódio na dose de 5 mg/kg por via oral a cada 24h. Na ausência de resposta clínica satisfatória e efeitos adversos, a dose foi aumentada para 10 mg/kg a cada 24h Os animais foram submetidos mensalmente a exame clínico e exames laboratoriais. Foram incluídos no estudo 28 gatos, sendo a maioria machos não castrados. Todos os gatos apresentavam lesão cutânea, principalmente úlceras (96,4%), sendo sua maior ocorrência nos membros anteriores (60,7%). Lesão em mucosa nasal foi observada em 78,8% dos casos e espirro (66,7%) foi o sinal respiratório mais observado. Do total de gatos incluídos, em 25% dos casos houve perda de seguimento e dois gatos (7,1%) vieram a óbito por causa desconhecida. Dos 19 gatos que concluíram o tratamento, seis (31,6%) obtiveram alta e em 13 casos (68,4%) foi observada falha terapêutica. Em seis gatos (31,6%) a dose foi aumentada para 10 mg/kg, dos quais dois (33,3%) tiveram como desfecho a alta. Dez gatos (52,6%) apresentaram efeitos adversos clínicos, sendo os mais frequentes emagrecimento (70%), hiporexia (50%) e apatia (40%). Foram observadas alterações nas dosagens bioquímicas séricas em três gatos (15,7%), nas quais dois animais (66,7%) apresentaram aumento leve de creatinina sérica e um (33,3%) apresentou aumento grave. A avaliação após a alta foi realizada em cinco animais. Destes, somente um gato apresentou recidiva de lesão em mucosa nasal, além de sinais respiratórios. Embora o esquema terapêutico proposto neste estudo tenha se mostrado seguro, a frequência de cura clínica foi baixa quando comparada ao itraconazol e ao iodeto de potássioSporotrichosis is an implantation mycosis, caused by species of the Sporothrix complex, that infects the human being and different animal species, especially cats. The treatment of cats with sporotrichosis is difficult due to several factors, like the limited therapeutic options, occurrence of treatment failures, and the high costs. Recently, the use of potassium iodide in a nonconventional pharmaceutical form (capsules) and lower dose than that established in the literature allowed obtaining satisfactory results. With regards to sodium iodide, few studies described its use and the effectiveness of this drug in capsules has not been reported. Therefore, the need to expand the treatment options and the possibility of reducing the adverse effects with the use of a lower dose than the one recommended inspired the elaboration of this study, which aimed to evaluate the therapeutic response to sodium iodide in cats with sporotrichosis. An observational cohort study was conducted from September 2014 to January 2016, with a population consisting of cats diagnosed with sporotrichosis confirmed by isolation of Sporothrix spp. and followed up at the Evandro Chagas National Institute of Infectious Diseases/Oswaldo Cruz Foundation. The treatment consisted of sodium iodide capsules orally administered at a dose of 5 mg/kg every 24 hours. In the absence of satisfactory clinical response and adverse effects, the dose was increased to 10 mg/kg every 24 hours. The animals were followed monthly for clinical and laboratory evaluations. The study included 28 cats, mostly unneutered males All cats had skin lesions, especially ulcers (96.4%), and a higher incidence in the forelimbs (60.7%). Lesion in the nasal mucosa was observed in 78.8% of cases and sneezing (66.7%) was the most frequentrespiratory sign. Twenty-five percent of the cases were lost to follow-up. Death occurred in two cases (7.1%). Among the 19 cats that completed the treatment, 31.6% (n=6) were discharged and the occurrence of treatment failure was observed in thirteen cases (68.4%). The dose was increased to 10 mg/kg in six cases (31.6%), of which two (33,3%) were discharged. Ten animals (52.6%) presented adverse clinical effects, being weight loss (70%), hyporexia (50%) and apathy (40%) the most common ones. Alterations in serum biochemical panels were observed in three cats (15.7%), two animals (66.7%) had a mild increase in serum creatinine and one (33.3%) severe increase. The evaluation after discharge was conducted in five animals. One cat presented recurrence of the lesion and respiratory signs in the nasal mucosa. Although the regimen proposed in this study has been shown to be safe, the clinical cure rate was similar to that previously described for the sodium iodide and lower, when compared to itraconazole and potassium iodid