RESUMO
We report the case of a 61-year-old female with Crohn's disease dependent on total parenteral nutrition who developed a central venous catheter bloodstream infection and septic arthritis, complicated further by osteomyelitis and persistent Candida glabrata fungemia. Fluconazole treatment led to persistent infection, and micafungin therapy failed with development of FKS-associated resistance. Infection responded after initiation of amphotericin B plus voriconazole. Echinocandin resistance is increasingly recognized, suggesting a role for alternative antifungal therapies.
Assuntos
Anfotericina B/uso terapêutico , Artrite Infecciosa/tratamento farmacológico , Candida glabrata/efeitos dos fármacos , Farmacorresistência Fúngica/efeitos dos fármacos , Equinocandinas/uso terapêutico , Osteomielite/tratamento farmacológico , Voriconazol/uso terapêutico , Antifúngicos/uso terapêutico , Artrite Infecciosa/microbiologia , Candida glabrata/metabolismo , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Proteínas Fúngicas/metabolismo , Humanos , Pessoa de Meia-Idade , Osteomielite/microbiologia , Terapia de Salvação/métodosRESUMO
OBJECTIVES: To evaluate the safety and efficacy of two dosing regimens of oral ibrexafungerp (formerly SCY-078), a novel orally bioavailable ß-glucan synthase inhibitor, in subjects with invasive candidiasis versus the standard of care (SOC) and to identify the dose to achieve target exposure (15.4 µM·h) in >80% of the intended population. METHODS: In a multinational, open-label study, patients with documented invasive candidiasis were randomized to receive step-down therapy to one of three treatment arms: two dosing regimens of novel oral ibrexafungerp or the SOC treatment following initial echinocandin therapy. Plasma samples were collected to evaluate exposure by population pharmacokinetic (PK) modelling. Safety was assessed throughout the study and global response at the end of treatment. RESULTS: Out of 27 subjects enrolled, 7 received ibrexafungerp 500 mg, 7 received ibrexafungerp 750 mg and 8 received the SOC. Five did not meet criteria for randomization. Population PK analysis indicated that an ibrexafungerp 750 mg regimen is predicted to achieve the target exposure in â¼85% of the population. The rate of adverse events was similar among patients receiving ibrexafungerp or fluconazole. Similar favourable response rates were reported among all groups: 86% (nâ=â6) in the ibrexafungerp 750 mg versus 71% (nâ=â5) in both the fluconazole and ibrexafungerp 500 mg treatment arms. The one subject treated with continued micafungin had a favourable global response. CONCLUSIONS: The oral ibrexafungerp dose estimated to achieve the target exposure in subjects with invasive candidiasis is 750 mg daily. This dose was well tolerated and achieved a favourable global response rate, similar to the SOC.
Assuntos
Antifúngicos/farmacocinética , Antifúngicos/uso terapêutico , Candidíase Invasiva/tratamento farmacológico , Equinocandinas/uso terapêutico , Glicosídeos/farmacocinética , Glicosídeos/uso terapêutico , Triterpenos/farmacocinética , Triterpenos/uso terapêutico , Administração Oral , Adulto , Idoso , Candida/efeitos dos fármacos , Equinocandinas/farmacocinética , Feminino , Fluconazol/farmacocinética , Fluconazol/uso terapêutico , Humanos , Masculino , Micafungina/farmacocinética , Micafungina/uso terapêutico , Testes de Sensibilidade Microbiana/métodos , Pessoa de Meia-IdadeRESUMO
Invasive candidiasis is a collective term that refers to a group of infectious syndromes caused by a variety of species of Candida, 5 of which cause most cases. Candidemia is the most commonly recognized syndrome associated with invasive candidiasis. Certain conditions may influence the likelihood for one species versus another in a specific clinical scenario, and this can have important implications for selection of antifungal therapy and the duration of treatment. Molecular diagnostic technology plays an ever-increasing role as an adjunct to traditional culture-based diagnostics, offering significant potential toward improvement in patient care.