RESUMO
BACKGROUND: Sertraline (SRT) is an antidepressant that has proven its activity in vitro against Cryptococcus, Coccidioides, Trichosporon and other fungi. Disseminated sporotrichosis, although rare, has a high mortality and its treatment is difficult and prolonged, often relying in combining two or more antifungals. AIMS: In our study we evaluate the antifungal activity of SRT, alone and in combination with itraconazole (ITC), voriconazole (VRC) and amphotericin B (AMB), against 15 clinical isolates of Sporothrix schenckii. METHODS: We used the broth microdilution method as described by the CLSI to test the susceptibility to antifungals, and the checkerboard microdilution method to evaluate drug interactions. RESULTS: The minimum inhibitory concentration (MIC) with SRT was in the range of 4-8µg/ml, while for AMB, VRC and ITC were 0.5-4µg/ml, 0.5-8µg/ml and 0.125-2µg/ml, respectively. In addition, SRT showed synergy with ITC in one strain, mainly additivity with VRC, and indifference with AMB in others. CONCLUSIONS: The MIC values with SRT for the isolates studied show the potential role of this drug as an adjuvant in the treatment of sporotrichosis, especially in disseminated or complicated cases.
Assuntos
Sertralina/farmacologia , Sporothrix/efeitos dos fármacos , Anfotericina B/administração & dosagem , Anfotericina B/farmacologia , Antifúngicos/administração & dosagem , Antifúngicos/farmacologia , Combinação de Medicamentos , Humanos , Itraconazol/administração & dosagem , Itraconazol/farmacologia , Testes de Sensibilidade Microbiana , Sporothrix/isolamento & purificação , Voriconazol/administração & dosagem , Voriconazol/farmacologiaRESUMO
PURPOSE: Cryptococcal meningitis is a potentially fatal fungal infection associated with a significant attributable morbidity and mortality, especially among HIV/AIDS patients. The first-line therapy for the treatment of this clinical entity is the combinatory therapy of amphotericin B plus flucytosine. However, the high cost, toxic effects, and limited repertoire of effective antifungal drugs have led to the investigation of novel molecules. This is a prospective, double-blinded, and randomized study performed in a Mexican tertiary care center to evaluate the antifungal activity of sertraline in the treatment of cryptococcal meningitis in HIV patients. METHODS: During June 2015-December 2016, patients were recruited and included in one of two study groups: group A was given standard antifungal treatment plus sertraline 200 mg/day, while group B was given standard antifungal plus placebo. Lumbar punctures were performed on days 0, 7, and 14 of the study, and cryptococcal antigenemia and quantitative fungal culture in cerebrospinal fluid at each time point were evaluated to measure the rate of fungal clearance. RESULTS: The fungal loads and cryptococcal antigenemia titers showed a marked tendency to decrease by day 14 in both groups. Otherwise, group B exhibited a slightly higher nonstatistical rate of fungal clearance (-0.2868 ± 0.08275 log CFU/ml/day) than group A (-0.2496 ± 0.08340 log CFU/ml/day). CONCLUSIONS: A statistical difference between study groups was not found. This is the first study in Latin America that reports the experience of using sertraline as an adjuvant in the antifungal management of cryptococcal meningitis in HIV patients.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Adjuvantes Farmacêuticos/uso terapêutico , Antifúngicos/uso terapêutico , Meningite Criptocócica/tratamento farmacológico , Sertralina/uso terapêutico , Adulto , Idoso , Método Duplo-Cego , Feminino , Infecções por HIV/complicações , Humanos , Masculino , Meningite Criptocócica/líquido cefalorraquidiano , México , Pessoa de Meia-Idade , Estudos Prospectivos , Centros de Atenção Terciária , Adulto JovemRESUMO
BACKGROUND: Candidemia is one of the most common nosocomial infections globally and it is associated with considerable excess mortality and costs. Abreast, biofilm-forming strains are associated with even higher mortality rates and poor prognosis for the patient. AIMS: To evaluate a possible association between the biofilm-forming capability of Candida bloodstream isolates and the clinical evolution in patients with candidemia. METHODS: An observational, retrospective study was conducted at a tertiary care university hospital during 9 years (2006-2015). The biofilm quantitation of the Candida bloodstream isolates was determined by crystal violet staining and XTT reduction assay. RESULTS: A total of 218 cases of candidemia had been diagnosed and 89 isolates were obtained. The mortality rate was 36% and the main risk factors were antibiotic exposure and the use of catheters. Candida tropicalis (52.8%) was the most frequent species, followed by Candida albicans (30.4%), Candida parapsilosis sensu stricto (10.1%), Candida orthopsilosis (3.4%), Candida krusei (2.2%) and Candida glabrata sensu stricto (1.1%). All the strains were biofilm producers, which is an important contribution to the patient's mortality. C. tropicalis showed the highest production of biomass biofilm, whereas C. glabrata exhibited the highest metabolic activity. CONCLUSIONS: This study contributes to expand the knowledge about the local epidemiology of candidemia and highlights the impact of Candida biofilm on patient's outcome.
Assuntos
Candida/fisiologia , Candidemia/microbiologia , Infecção Hospitalar/microbiologia , Adulto , Biofilmes , Candida/isolamento & purificação , Candidemia/sangue , Criança , Pré-Escolar , Infecção Hospitalar/sangue , Estudos Transversais , Progressão da Doença , Suscetibilidade a Doenças , Feminino , Hospitais Universitários/estatística & dados numéricos , Humanos , Lactente , Masculino , México , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Centros de Atenção Terciária/estatística & dados numéricosRESUMO
Cryptococcus neoformans infection is an important cause of meningitis in HIV/AIDS endemic regions. Antifungals for its management include amphotericin B, flucytosine, and fluconazole. Recently, treatment of this mycosis with sertraline has been studied with variable clinical outcomes. The aim of the study was to assess the in vitro antifungal effect of sertraline against clinical isolates of Cryptococcus spp. as well as its in vivo activity in a murine model of cryptococcal meningoencephalitis. The in vitro susceptibility to fluconazole, amphotericin B, voriconazole and sertraline of 153 Cryptococcus spp. strains were evaluated according to CLSI procedures. Fungal tissue burden, serum antigenaemia and histopathology, together with the therapeutic efficacy of amphotericin B (3 mg/kg), fluconazole (15 mg/kg), and sertraline (3, 10, and 15 mg/kg) were evaluated in mice intracranially inoculated with one isolate of Cryptococcus neoformans. All strains were susceptible to the antifungals studied and exhibited growth inhibition with sertraline at clinically relevant concentrations. Sertraline at a dose of 15 mg/kg reduced the fungal burden in the brain and spleen with an efficacy comparable to that of fluconazole. In conclusion, sertraline exhibited an excellent in vitro-in vivo anti-cryptococcal activity, representing a possible new alternative for the clinical management of meningeal cryptococcosis.
Assuntos
Antifúngicos/administração & dosagem , Antifúngicos/farmacologia , Criptococose/tratamento farmacológico , Criptococose/microbiologia , Cryptococcus neoformans/efeitos dos fármacos , Sertralina/administração & dosagem , Sertralina/farmacologia , Estruturas Animais/microbiologia , Animais , Contagem de Colônia Microbiana , Criptococose/patologia , Cryptococcus neoformans/isolamento & purificação , Modelos Animais de Doenças , Fungemia/microbiologia , Histocitoquímica , Humanos , Masculino , Camundongos , Resultado do TratamentoRESUMO
Chromoblastomycosis is a slowly growing chronic cutaneous mycosis associated with a variety of cutaneous lesions. Extra-dermal involvement is rare. A 58-year-old man was admitted to the hospital with nausea, vomiting, weakness and a history of weight loss. On inspection, he had a large verrucous mass in the sacral region, and two large subcutaneous nodules in the anterior thoracic wall. He claimed the lesions were several years old. Biopsy and histological studies were positive for chromoblastomycosis. Routine chest radiography showed hilar enlargement, and a chest computed tomography was ordered. Pulmonary nodules were evident, and endoscopically acquired samples were also positive for chromoblastomycosis. Extra-dermal and systemic involvement in chromoblastomycosis is exceedingly rare and often associated with immunosuppression. There is only one other case of pulmonary chromoblastomycosis reported in the published work.