ABSTRACT
La cromoblastomicosis es una micosis de implantación crónica y progresiva causada por diversos hongos de la familia Dematiaceae. En Latinoamérica, las especies en-contradas con más frecuencia son Fonsecaea pedrosoi y Cladophialophora carrionii. El tratamiento de esta micosis puede ser un desafío por la falta de respuesta y la recidiva, en especial en individuos con lesiones crónicas y extensas.Se presenta un individuo con recaída de cromoblastomico-sis (causada por Fonsecaea pedrosoi) en miembro inferior derecho que había realizado tratamiento incompleto con terbinafina e itraconazol. El paciente respondió de mane-ra favorable al retratamiento con itraconazol y terbinafina combinado con resección quirúrgica parcial de la lesión e injerto de piel en sitio quirúrgico
Chromoblastomycosis is a chronic and subcutaneous mycosis caused by various dematiaceous fungi, In Latin America, the most frequently found species are Fonsecaea pedrosoi and Cladophialophora carrionii.Treatment is a challenge because of the lack of response and recurrence in in some cases, especially in patients with extensive and chronic lesions.We report an individual with relapse of chromoblastomycosis (by Fonsecaea pedrosoi) in the right lower limb, who had undergone incomplete treatment with terbinafine and itraconazole. The patient responded favorably to retreatment with itraconazole and terbinafine combined with partial surgical resection of the lesion and skin grafting at the surgical site.
Subject(s)
Humans , Male , Middle Aged , Chromoblastomycosis/therapy , Itraconazole/therapeutic use , Terbinafine/therapeutic use , FonsecaeaABSTRACT
La terbinafina es un fármaco que puede inducir daño hepático agudo. Presentamos el caso de un paciente varón de 40 años que desarrolló disfunción hepática después de 35 días de tratamiento con terbinafina por onicomicosis. El estudio anátomo patológico demostró: hepatitis aguda en resolución, además de ductopenia y colestasis. Estos hallazgos, sin el antecedente de hepatitis viral o autoinmune, son consistentes con el diagnóstico de daño hepático inducido por drogas (DILI). En este reporte presentamos el primer caso en nuestro país de un paciente que es afectado por una enfermedad hepática aguda: injuria hepática inducida por terbinafina, al cual se le asoció posteriormente infección por SARS-CoV-2 en el contexto de una pandemia.
Terbinafine is a drug that can induce acute liver damage. We present the case of a 40-year-old male patient who developed liver dysfunction after 35 days of terbinafine treatment for onychomycosis. The anatomopathological study showed: acute hepatitis in resolution, in addition to ductopenia and cholestasis. These findings, without a history of viral or autoimmune hepatitis, are consistent with the diagnosis of drug-induced liver damage (DILI). In this report we present the first case in our country of a patient who is affected by an acute liver disease: terbinafine-induced liver injury, to which SARS-CoV-2 infection was later associated in the context of a pandemic.
ABSTRACT
Resumen Objetivo: Analizar la susceptibilidad de N. dimidiatum ante el efecto combinado de itraconazol y terbinafina. Métodos: Se determinó la concentración mínima inhibitoria y la concentración inhibitoria fraccionada in vitro, mediante el método del tablero de ajedrez, a 15 aislamientos clínicos provenientes de onicomicosis de diferentes pacientes, todos positivos por N. dimidiatum. Se prepararon ensayos por duplicado con diluciones combinadas de los antifúngicos y se evaluó el efecto de ambos fármacos. Resultados: La concentración mínima inhibitoria promedio de solo itraconazol aplicado a los aislamientos fue de 30,83 μg/mL y de 4,49 μg/mL combinado con terbinafina. La concentración mínima inhibitoria promedio de solo terbinafina fue de 0,33 μg/mL y de 0,07 μg/mL combinada con itraconazol. Hay diferencias estadísticamente significativas entre las concentraciones mínimas inhibitorias promedio de los antifúngicos analizados en solitario respecto de las concentraciones mínimas inhibitorias combinadas; para itraconazol (t = 2,958; gl = 14; p = 0,01) y (t = 4,721; gl = 14; p < 0,001) para terbinafina. El uso combinado evidenció 40 % de sinergismo. Conclusiones: La combinación itraconazol-terbinafina presentó un efecto sinérgico total para inhibir el crecimiento de N. dimidiatum; esto ofrece una alternativa terapéutica en el tratamiento de las onicomicosis.
Abstract Aim: Study the combined susceptibility patterns of Neoscytalidium dimidiatum to the effect of Itraconazole and Terbinafine. Background: The Minimum Inhibitory Concentration and Fractional Inhibitory Concentration were determined in vitro by the chessboard method for 15 clinical isolates of onychomycosis, from different patients, all positives for N. dimidiatum. Duplicated trials were prepared with combined dilutions of antifungals and the effect of both drugs was evaluated. Results: The average Minimum Inhibitory Concentration of Itraconazole when applied alone for the isolates was 30.83 μg/mL and 4.49 μg/mL when combined with Terbinafine. The average Minimum Inhibitory Concentration of Terbinafine alone was 0.33 μg/mL and 0.07 μg/mL when combined with Itraconazole. Statistically significant differences were found between the average Minimum Inhibitory Concentrations of the antifungals analyzed alone versus the Minimum Inhibitory Concentrations obtained by mixing both compounds. That is for Itraconazole (t = 2,958; gl = 14; p = 0,01) and (t = 4,721; gl = 14; p <0,001) for Terbinafine. Combined use showed 40 % synergism. Conclusions: The Itraconazole-Terbinafine combination had synergistic effect to inhibit the growth of N. dimidiatum, which offers a therapeutic alternative in the treatment of onychomycoses caused by this fungus.
Subject(s)
Onychomycosis/drug therapy , Itraconazole/therapeutic use , Terbinafine/therapeutic use , Costa RicaABSTRACT
La micosis ungueal es la principal causa de lesión ungueal y afecta entre el 2,5 y el14% de la población; la elección del tratamiento se basa principalmente en la identificación del agente causal por cultivo; la enfermedad tiene una alta tasa de resistencia y recurrencia terapéutica definidas como falta de aclaramiento de al menos el 25% de la uña o al aislamiento del hongo, determinable solo hasta el final del tratamiento o meses después. La prueba de sensibilidad antifúngica no se ha establecido como un método rutinario de laboratorio, su implementación podría reducir los riesgos de toxicidad por medicamentos innecesariamente instaurados, elevar la tasa de respuesta al tratamiento, medir la tasa de resistencia de los hongos a los antifúngicos disponibles, utilizar antimicóticos frente a los cuales sí haya sensibilidad por parte del agente micótico y reducir costos de terapia. Objetivo: Determinar la sensibilidad in vitro de tres fármacos antifúngicos en los agentes etiológicos aislados de lesiones micóticas ungueales. Tipo de estudio: Descriptivo. Población de referencia: Adultos con diagnóstico clínico de micosis ungueal de la ciudad de Manizales (Caldas, Colombia) de quienes se aislaron diferentes especies de agentes micóticos. Materiales y Métodos: Para la realización de los ensayos con los antifúngicos se emplearon los métodos propuestos por el CLSI en los protocolos M27-A2 y M27-S3 para levaduras y el M38-A2 para hongos miceliales. Se hizo análisis estadístico mediante el programa SPSS, aplicando el test de Student para el análisis de frecuencias y pruebas no paramétricas para el análisis de los resultados obtenidos con los antifúngicos. Resultados obtenidos: Los dermatofitos (T. rubrum, T. mentagrophytes y T. tonsurans) mostraron mayor sensibilidad a terbinafina e itraconazol con MIC50 de 0,0156 ug/ml y 0,0625 ug/ml, respectivamente. Las levaduras y hongos miceliales no dermatofitos tuvieron elevadas concentraciones inhibitorias mínimas para los tres fármacos. La mayor tasa de resistencia in vitro (fluconazol 100%, terbinafina 25%, itraconazol 67%) se observó en el grupo de los hongos miceliales no dermatofitos (Fusarium spp., Penicillium spp., Helmintosporium spp., Aspergillus spp., Acremonium spp. y Scopulariopsis spp.). Conclusiones: Aunque no existen hasta la fecha puntos de corte aplicables a la práctica clínica, ni es clara la correlación de los resultados con el desenlace clínico, la estandarización del test de sensibilidad antifúngica in vitro abre la posibilidad de hacer comparaciones con otros estudios y vigilancia de resistencias emergentes.
The onychomycosis is the main cause of nail injury and affects between 2.5 and 14% of the population; the election of treatment is based primarily on the identification of the causative agent by culture. The disease has a high rate of recurrence and therapeutic resistance defined by lack of clearance of at least 25% of the nail or the isolation of fungus, determinable only until the end of treatment or months later. Antifungal susceptibility testing has not been established as a routine laboratory method; its implementation could reduce the risk of drug toxicity by unnecessary administration, raise the rate of response to treatment, measure the rate of resistance of fungi to antifungal agents available, use of antifungal against which there is sensitivity by the mycotic agent and reduce costs. Objective: To determine the in vitro susceptibility of three antifungal drugs in etiologic agents isolated from fungal nail lesions. Study type: Descriptive. Reference population: Adults with a clinical diagnosis of nail mycosis in the city of Manizales, Caldas, Colombia from whom different species of mycotic agents were isolated. Materials and Methods: To perform tests with antifungal agents, the methods proposed by the CLSI in the M27-A2 and M27-S3 protocols for yeasts and M38-A2 for mycelial fungi were used. The statistical analysis was done using the SPSS program, applying Student's test for frequency analysis and non-parametric tests for the results obtained with antifungals. Results: The dermatophytes (T. rubrum, T. mentagrophytes and T. tonsurans) showed increased sensitivity to terbinafine and itraconazole with MIC50 of 0.0156 mg/ml and 0.0625 mg/ml respectively. Yeasts and no dermatophytes mycelial fungi had elevated MICs for all three drugs. The highest rate of resistance in vitro (fluconazole 100%, terbinafine 25%, itraconazole 67%) was observed in the group of non-dermatophyte filamentous fungi (Fusarium spp., Penicillium spp., Helminthosporium spp., Aspergillus spp., Scopulariopsis spp. and Acremonium spp.). Conclusions: Although to date breakpoints applicable to clinical practice do not exist and clear correlation of the results with the clinical outcome is not clear either, the standardization of the antifungal susceptibility test in vitro opens the possibility to make comparisons with other studies and surveillance of emerging resistance.
ABSTRACT
La tinea capitis (tiña de la cabeza) es una infección por dermatofitos del folículo piloso del cuero cabelludo y la piel en relación. Afecta principalmente a niños y su prevalencia varía entre regiones, siendo el Microsporum canis el agente más aislado en todo el mundo. Existen diversos medicamentos para el tratamiento de esta patología con reconocida eficacia terapéutica. Sin embargo, la disponibilidad, costos y tolerabilidad a algunos de estos hace limitado su uso en la población pediátrica. Con el objetivo de evaluar desde el punto de vista clínico y determinar la susceptibilidad in vitro a la terbinafina siguiendo las recomendaciones del Clinical Laboratory Standards Institute, de acuerdo al documento M38-A2, se diseñó una investigación observacional, descriptiva, experimental y prospectiva, en pacientes pediátricos con diagnóstico de tinea capitis por Microsporum canis de la consulta de micología del servicio de Dermatología del Hospital Universitario de Caracas- Venezuela. Fueron evaluados 72 pacientes, con edad entre menos de 1 y 11 años, 73,61 % fueron masculinos. En la mayoría la dermatofitosis se presentó de forma clínica tonsurante, el examen directo micológico evidenció el ataque ectothrix al pelo en el 98,6 % de los casos. 69,60 % tuvieron una evolución satisfactoria una vez instaurado el tratamiento con terbinafina oral. Según la actividad in vitro la Terbinafina resultó eficaz contra el 100 % de los aislados, con un rango de concentración mínima inhibitoria entre menos de 0,0019 µg/ml y 0,0156 µg/ml. Se concluye que la caracterización desde el punto de vista clínico y el conocimiento de los patrones de susceptibilidad a los antifúngicos se hace necesaria para la adecuada terapéutica.
Tinea capitis (ringworm of the head) is a dermatophyte infection of the scalp hair follicle and skin on. It affects mainly childrens and its prevalence varies between regions, Microsporum canis is the most isolated agent worldwide. There are different medications to treat this condition with proven therapeutic efficacy. However, the availability, cost and tolerability of these makes some limited use in the pediatric population. With the aim to evaluate from the clinical viewpoint and determine the in vitro susceptibility to terbinafine as recommended by the Clinical Laboratory Standards Institute, according to the document M38-A2, was designed an observational, descriptive, experimental and prospectively investigation, in pediatric patients diagnosed with tinea capitis by Microsporum canis from the consultation of service of Dermatology, University Hospital of Caracas, Venezuela. Were assessed 72 patients, aged less than 1 and 11 years, 73.61% were male. In most of dermatophytosis presented clinically tonsurans, direct mycological examination showed the hair ectothrix attack in 98.6% of cases. 69.60% had a satisfactory evolution once established treatment with oral terbinafine. According to the in vitro activity of terbinafine was effective against 100% of isolates with a minimum inhibitory concentration range from less than 0.0019 According to the in vitro activity of terbinafine was effective against 100% of isolates with range of values for minimum inhibitory concentration from less than 0.0019 µg/ml and 0.0156 µg/ml. Is concluded that the characterization from the clinical perspective and knowledge of the patterns of susceptibility to antifungal agents is necessary for proper treatment.
Subject(s)
Humans , Male , Female , Tinea Capitis , Disease Susceptibility , Terbinafine , Microsporum , Microbial Sensitivity Tests , MycologyABSTRACT
O estudo objetivou avaliar a atividade in vivo do itraconazol e terbinafina no tratamento da esporotricose cutânea experimental. Foram utilizados 80 ratos Wistar divididos em quatro grupos (TERB20, TERB30, ITRA e CONT) inoculados no coxim plantar esquerdo com 0,2ml de solução contendo 2x103 células de Sporothrix schenckii/ml e tratados com terbinafina (20 e 30mg/kg), itraconazol (10mg/kg) e placebo durante 13 semanas. As lesões do sítio de inoculação foram avaliadas e mensuradas semanalmente, assim como a disseminação das mesmas. Após foi realizada análise micológica e histopatológica. Os resultados demonstraram que os animais do grupo ITRA diferiram estatisticamente em todos os parâmetros avaliados em relação ao CONT. Em relação à terbinafina, não houve diferenças estatísticas entre os grupos tratados e controle. Pode-se confirmar a boa atividade do itraconazol no tratamento da esporotricose e a pouca eficácia da terbinafina nas doses utilizadas, sendo necessários mais estudos com este antifúngico.
The aim of this study was to evaluate the in vivo activity of itraconazole and terbinafine for treating experimental cutaneous sporotrichosis. Eighty Wistar rats were used, divided into four groups (TERB20, TERB30, ITRA and CONT). They were inoculated in the left plantar pad with 0.2 ml of solution containing 2x10³ cell/ml of Sporothrix schenckii and treated with terbinafine (20 and 30 mg/kg), itraconazole (10 mg/kg) or placebo for 13 weeks. The lesions at the inoculation site were evaluated and measured weekly, along with their dissemination. Mycological and histopathological analyses were performed subsequently. The results showed that the animals in the ITRA group differed statistically in all parameters evaluated, in relation to CONT. For terbinafine, there were no statistical differences between the treated and control groups. It could be confirmed that itraconazole presented good activity for treating sporotrichosis, while terbinafine was ineffective for this disease at the doses used. However, more studies on the latter antifungal agent are needed.
Subject(s)
Animals , Male , Rats , Antifungal Agents/therapeutic use , Itraconazole/therapeutic use , Naphthalenes/therapeutic use , Sporotrichosis/drug therapy , Drug Evaluation, Preclinical , Rats, Wistar , Sporotrichosis/pathologyABSTRACT
O tratamento de eleição para a esporotricose na sua forma cutânea é o itraconazol. Este é um fármaco eficaz e com boa tolerância pelos pacientes, mas apresenta uma série de interações medicamentosas que dificultam o seu uso. A terbinafina, um derivado alilamina com atividade fungicida, tem seu uso descrito no tratamento da esporotricose cutânea com dosagens variáveis (250 mg a 1 g/dia). Entretanto, a posologia ideal não está estabelecida. Este estudo teve como objetivo avaliar a efetividade e segurança da terbinafina na dosagem de 250 mg no tratamento da esporotricose cutânea. Foram realizados dois estudos complementares em pacientes com esporotricose cutânea com terbinafina 250 mg/dia no período de janeiro de 2005 a dezembro de 2008: 1) um estudo descritivo em pacientes com contra-indicação ao uso do itraconazol ou interação medicamentosa de moderada a grave, 2) um estudo analítico de coorte bidirecional, comparando com o itraconazol 100 mg/dia. O grupo itraconazol foi selecionado randomicamente do banco de dados do serviço, após pareamento por idade e forma clínica. O Sporothrix schenckii foi isolado em cultivo de todos os pacientes, com idade entre 18 a 70 anos e que foram submetidos ao protocolo de atendimento que incluiu avaliação clínica, hemograma e bioquímica e consultas com periodicidade determinada...
No estudo descritivo, foram selecionados 50 pacientes que apresentavam comorbidades e utilizaramm medicamentos em que não era possível o uso de itraconazol (36% psicolépticos; 28% hipoglicemiantes; 18% hipolipêmicos; 16% bloqueadores do canal de cálcio; 8% anticonvulsivantes; 6,3% cardiotrópicos; 6,3% antiácidos e anti-parkinsonianos 2,1%). A maioria (96%) curou em 14 semanas, variando de 2 a 42. A terbinafina foi suspensa em um caso por reação de hipersensibilidade (erupção cutânea) e não houve recidiva da micose. No estudo analítico de coorte bidirecional, foram incluídos 55 pacientes no grupo da terbinafina e 249 do itraconazol. A cura ocorreu respectivamente em 51 (92,7%) e 229 (92%) em média de 11 e 10,5 semanas. Em dois pacientes foi necessário o aumento da dose da terbinafina para 500 mg por não resposta e uma paciente apresentou recidiva. No grupo do itraconazol dois necessitaram aumento da dose e três apresentaram recidiva. Os efeitos adversos foram quatro (7,3%) sem necessidade de suspensão do medicamento no grupo terbinafina e 19 (7,6%) com sua suspensão em dois pacientes no grupo itraconazol. A terbinafina na dose de 250 mg/dia é uma opção para o tratamento da esporotricose cutânea sendo efetiva e bem tolerada...
Subject(s)
Humans , Itraconazole , Sporothrix , SporotrichosisABSTRACT
Itraconazole is currently considered the drug of choice to treat the diverse clinical presentation of sporotrichosis. On the other hand terbinafine by virtue of its excellent in vitro activity is under comparative evaluation for its therapeutic potential for a wide range of fungal infections. In this study, our aim was to determine the in vivo efficacy of terbinafine and itraconazole on a experimental model of systemic sporotrichosis. 120 rats Wistar received an injection of 2x10³ S. schenckii cells by via the lateral tail vein. After 3 days the animals were treated with terbinafine (250mg/kg) and itraconazole (100 mg/kg) and their respective diluents. In our model, terbinafine and itraconazole were effective in reducing the number of clinical lesions and positive organ cultures. There was statistical difference between the groups treated with the antifungals in relation to the control groups (p<0,05) concerning the clinical alterations, anatomic-pathological findings and in the positive organ cultures of the agent, being that the treated animals resulted in the absence and/or reduction of all the evaluated parameters. As for the treatments, terbinafine showed similar or higher activity that itraconazole in the evaluation of the testicle alteration (p=0,0004), as well as in the positive organ cultures of microorganism from the organ (p=0,0142). With these results it is possible to conclude that the antifungals studied are effective in the treatment of experimental systemic sporotrichosis.
Itraconazol é atualmente considerado a droga de escolha para o tratamento das diferentes formas clínicas da esporotricose. Por outro lado a terbinafina devido a sua excelente atividade in vitro está sendo avaliada quanto ao seu potencial terapêutico frente a diversas infecções fúngicas. O objetivo deste estudo foi determinar a eficácia in vivo da terbinafina e itraconazol em um modelo de esporotricose experimental sistêmica. 120 ratos Wistar receberam uma injeção de 2x10³ células de S. schenckii pela veia lateral da cauda. Após 3 dias os animais foram tratados com terbinafina (250mg/kg) e itraconazol (100mg/kg) e os seus respectivos diluentes. No modelo experimental estudado, a terbinafina e itraconazol se mostraram efetivos reduzindo o número de sintomas clínicos e retroisolamento positivo para o agente. Houve diferenças estatísticas entre os grupos tratados com os antifúngicos em relação aos grupos controle (p<0,05) nas alterações clínicas, achados anatomopatológicos e no retroisolamento do agente, sendo que os animais tratados resultaram na ausência e/ou diminuição de todos os parâmetros avaliados. Quanto aos tratamentos a terbinafina se mostrou com atividade similar ou superior ao itraconazol quando avaliado as alterações anatomopatológicos do testículo (p=0,0004), assim como no retoisolamento do órgão (p=0,0142). Com estes resultados permite-se concluir que os antifúngicos estudados são efetivos no tratamento da esporotricose sistêmica experimental.