RESUMO
We report the recent isolation of Cryptococcus laurentii from the feces of a patient with Hodgkin's lymphoma who underwent autologous hematopoietic stem cell transplant (HSCT). The organism was identified using microscopic morphology, cultural characteristics, and biochemical tests including sugar assimilation. Minimum inhibitory concentration of various antifungals was determined by microbroth dilution method. The recovery of pure culture of C. laurentii from stool culture, and the patient's response to treatment with voriconazole support its potential etiological role. To the best of our knowledge, we report the first case of diarrhea caused by C. laurentii in an HSCT recipient.
Assuntos
Antifúngicos/uso terapêutico , Criptococose/microbiologia , Cryptococcus/isolamento & purificação , Diarreia/microbiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença de Hodgkin/cirurgia , Voriconazol/uso terapêutico , Administração Intravenosa , Administração Oral , Adulto , Antibioticoprofilaxia , Antifúngicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteína C-Reativa/análise , Carmustina/efeitos adversos , Carmustina/uso terapêutico , Criptococose/sangue , Criptococose/tratamento farmacológico , Citarabina/efeitos adversos , Citarabina/uso terapêutico , Diarreia/sangue , Diarreia/tratamento farmacológico , Etoposídeo/efeitos adversos , Etoposídeo/uso terapêutico , Fezes/microbiologia , Fluconazol/uso terapêutico , Humanos , Melfalan/efeitos adversos , Melfalan/uso terapêutico , Testes de Sensibilidade Microbiana , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Transplante Autólogo/efeitos adversos , Voriconazol/administração & dosagemRESUMO
Cryptococcus albidus and Cryptococcus laurentii are uncommon species of this genus that in recent decades have increasingly caused opportunistic infections in humans, mainly in immunocompromised patients; the best therapy for such infection being unknown. Using a murine model of systemic infection by these fungi, we have evaluated the efficacy of amphotericin B (AMB) at 0.8 mg/kg, administered intravenously, fluconazole (FLC) or voriconazole (VRC), both administered orally, at 25 mg/kg and the combination of AMB plus VRC against three C. albidus and two C. laurentii strains. All the treatments significantly reduced the fungal burden in all the organs studied. The combination showed a synergistic effect in the reduction in fungal load, working better than both monotherapies. The histopathological study confirmed the efficacy of the treatments.
Assuntos
Antifúngicos/uso terapêutico , Criptococose/tratamento farmacológico , Criptococose/microbiologia , Cryptococcus/efeitos dos fármacos , Administração Intravenosa , Administração Oral , Anfotericina B/uso terapêutico , Animais , Criptococose/sangue , Modelos Animais de Doenças , Sinergismo Farmacológico , Quimioterapia Combinada , Fluconazol/uso terapêutico , Hospedeiro Imunocomprometido , Pulmão/microbiologia , Camundongos , Testes de Sensibilidade Microbiana , Baço/microbiologia , Voriconazol/uso terapêuticoRESUMO
We studied the pharmacokinetics and efficacy of BAY R3783, a new antifungal azole compound, in rabbits and compared it with fluconazole and itraconazole. BAY R3783 has at least two active metabolites, BAY U3624 and BAY U3625. We measured serum concentrations of all three compounds; the peak serum level for the parent compound was approximately two hours post dose. BAY R3783 and its metabolites also crossed the blood-CSF barrier; the mean CSF level of BAY R3783 was 30.5% of simultaneous serum levels. The in-vivo activity of the azoles was compared in a model of cryptococcal meningitis in immunosuppressed rabbits. BAY R3783, fluconazole and itraconazole all reduced yeast counts in the CSF with equal efficacy over ten days of therapy at 100 mg/day. In this model, BAY R3783 was effective in the treatment of cryptococcal meningitis.