Invasive fungal infections are a major challenging problem in the management of febrile neutropenia (FN) in patients with hematologic malignancies. Liposomal amphotericin B (L-AmB) or micafungin (MCFG) has been widely...Invasive fungal infections are a major challenging problem in the management of febrile neutropenia (FN) in patients with hematologic malignancies. Liposomal amphotericin B (L-AmB) or micafungin (MCFG) has been widely used as a first-line empirical antifungal therapy for suspected fungal infection in such patients. However, there are several issues in patients receiving these agents: drug related toxicities for L-AmB and breakthrough fungal infections for MCFG. In order to make the best use of these 2 agents, we conducted a prospective study of sequential therapy from MCFG to L-AmB, and evaluated the efficacy and safety of this strategy in FN patients with hematologic malignancies. A total of 18 patients were enrolled, and 11 patients who fulfilled the protocol defined criteria were evaluated. Underlying diseases consisted of acute leukemia (n = 9), non-Hodgkin lymphoma (n = 1), and myelodysplastic syndrome (n = 1). Treatment success was achieved in 8 patients (72.7%). Drug-related adverse events occurred in 8 patients (72.7%). All of those adverse events except one case were below grade 2. Three patients required discontinuation of L-AmB. Although our empirical antifungal sequential therapy seems to be encouraging for antibiotics-refractory FN in patients with hematologic malignancies, further investigation in large-scale studies is warranted.展开更多
The objective of our study was to explore the possibility of the antifungal efficacy of various micafungin dosage regimens against <i>Candida spp</i> in HIV positive patients with EC. According to pharmaco...The objective of our study was to explore the possibility of the antifungal efficacy of various micafungin dosage regimens against <i>Candida spp</i> in HIV positive patients with EC. According to pharmacokinetic/pharmacodynamics parameters of micafungin in HIV positive patients and MICs distribution of micafungin against <i>Candida spp</i>. in published studies, the dosage regimens of micafungin were 50, 100 and 150 mg QD iv. Monte Carlo Simulation analysed the probability of target attainment and cumulative fraction of response. The results showed that micafungin has good antifungal effect in treating HIV positive patients with EC when pathomycetes are <i>Candida albicans</i>, <i>Candida glabrata</i> or <i>Candida tropicalis</i>, in dosage at 100 mg QD and 150 mg QD.展开更多
Micafungin is an efficacious and well-tolerated echinocandin with in vitro and in vivo activity against a broad range of Candida species. The objective of this randomized, double-blind study was to examine the pharmac...Micafungin is an efficacious and well-tolerated echinocandin with in vitro and in vivo activity against a broad range of Candida species. The objective of this randomized, double-blind study was to examine the pharmacokinetic parameters of micafungin and its metabolites in a subset of adult patients with invasive candidiasis or candidemia. The study was conducted at 27 sites in four countries, including eight in Europe. Micafungin 100 mg/day or liposomal amphotericin B 3 mg/kg/day were administered once daily as a 1-hour infusion in a blinded manner. The minimum duration of therapy was 14 days. To define plasma analyte (micafungin and metabolites) concentration-time profiles, serial blood samples were collected after the first dose (Day 1), and at the end of therapy (EOT). For patients who received treatment for longer than 2 weeks, an additional profile was obtained during Week 2. To determine plasma trough analyte concentrations, blood samples were collected immediately prior to dosing on Day 2, Week 2, and EOT. In 20 evaluable, micafungin-treated patients, plasma micafungin concentrations peaked at completion of the 1-hour infusion and then declined biexponentially. Plasma concentrations of the micafungin metabolites (M-1, M-2, and M-5) remained low (<1 μg/mL) throughout the study. The mean half-life and clearance of micafungin were largely unchanged with repeated dosing up to 28 days, and no evidence of micafungin accumulation was observed. These data provide further support for the predictability of micafungin pharmacokinetics in adult patients with invasive candidiasis and candidemia.展开更多
Neutropenia with fever is a special group of patients. Due to low immune function, inflammation-related clinical symptoms and signs are often not obvious, and pathogenic bacteria and infection focus are not clear. Fev...Neutropenia with fever is a special group of patients. Due to low immune function, inflammation-related clinical symptoms and signs are often not obvious, and pathogenic bacteria and infection focus are not clear. Fever may be the only sign of infection. If appropriate antimicrobial treatment is not given in time, infection-related mortality is high. In our study, we aimed to optimize the dosage regimen of Micafungin in children with febrile neutropenic against Candida spp. by Mote Carlo Simulation (MCS). Pharmacokinetic parameters and microbiological data of Micafungin were collected. Then we used MCS to calculate Probability of Target Attainment (PTA) and Cumulative Fraction of Response (CFR). With dosages of 0.5 mg/kg, 1 mg/kg, 1.5 mg/kg, 2 mg/kg, 3 mg/kg, and 4 mg/kg in oral group and dosages of 100 mg, and 200 mg in intravenous administration, all have different degree of antifungal effect. But when the dosage regimen was 50 mg IV, the therapeutic effect of Micafungin against Candida spp. was not good.展开更多
目的了解新型抗真菌药物米卡芬净(micafungin,MFG)对分离自中国的念珠菌和曲霉临床株的体外抑菌活性。方法参照CLSI(Clinical and Laboratory Standards Institute,以前为NCCLS)制定的M27-A2和M38-A方案测定86株念珠菌和35株曲霉的最低...目的了解新型抗真菌药物米卡芬净(micafungin,MFG)对分离自中国的念珠菌和曲霉临床株的体外抑菌活性。方法参照CLSI(Clinical and Laboratory Standards Institute,以前为NCCLS)制定的M27-A2和M38-A方案测定86株念珠菌和35株曲霉的最低抑菌浓度(MIC)或最低有效浓度(MEC)。结果MFG对大多数念珠菌属和曲霉属均有较好的抑菌作用。对念珠菌属的MIC90从高到低依次为:氟康唑(FLC)敏感的白念珠菌、热带念珠菌、光滑念珠菌为0.125μg/ml,FLC耐药和剂量依赖敏感株为0.25μg/ml,克柔念珠菌为0.5μg/ml,近平滑念珠菌8μg/ml,季也蒙念珠菌>16μg/ml。MFG对烟曲霉的MEC90为≤0.03μg/ml,对非烟曲霉的曲霉属MEC90为0.06μg/ml。MFG与唑类药物、两性霉素B(AMB)不存在交叉耐药,对FLC耐药的念珠菌、伊曲康唑耐药的曲霉、AMB不敏感的曲霉均有好的抑菌活性。结论MFG对多数念珠菌属和曲霉属(包括对唑类耐药和AMB不敏感的菌株)有较好的体外抑菌作用。展开更多
文摘Invasive fungal infections are a major challenging problem in the management of febrile neutropenia (FN) in patients with hematologic malignancies. Liposomal amphotericin B (L-AmB) or micafungin (MCFG) has been widely used as a first-line empirical antifungal therapy for suspected fungal infection in such patients. However, there are several issues in patients receiving these agents: drug related toxicities for L-AmB and breakthrough fungal infections for MCFG. In order to make the best use of these 2 agents, we conducted a prospective study of sequential therapy from MCFG to L-AmB, and evaluated the efficacy and safety of this strategy in FN patients with hematologic malignancies. A total of 18 patients were enrolled, and 11 patients who fulfilled the protocol defined criteria were evaluated. Underlying diseases consisted of acute leukemia (n = 9), non-Hodgkin lymphoma (n = 1), and myelodysplastic syndrome (n = 1). Treatment success was achieved in 8 patients (72.7%). Drug-related adverse events occurred in 8 patients (72.7%). All of those adverse events except one case were below grade 2. Three patients required discontinuation of L-AmB. Although our empirical antifungal sequential therapy seems to be encouraging for antibiotics-refractory FN in patients with hematologic malignancies, further investigation in large-scale studies is warranted.
文摘The objective of our study was to explore the possibility of the antifungal efficacy of various micafungin dosage regimens against <i>Candida spp</i> in HIV positive patients with EC. According to pharmacokinetic/pharmacodynamics parameters of micafungin in HIV positive patients and MICs distribution of micafungin against <i>Candida spp</i>. in published studies, the dosage regimens of micafungin were 50, 100 and 150 mg QD iv. Monte Carlo Simulation analysed the probability of target attainment and cumulative fraction of response. The results showed that micafungin has good antifungal effect in treating HIV positive patients with EC when pathomycetes are <i>Candida albicans</i>, <i>Candida glabrata</i> or <i>Candida tropicalis</i>, in dosage at 100 mg QD and 150 mg QD.
文摘Micafungin is an efficacious and well-tolerated echinocandin with in vitro and in vivo activity against a broad range of Candida species. The objective of this randomized, double-blind study was to examine the pharmacokinetic parameters of micafungin and its metabolites in a subset of adult patients with invasive candidiasis or candidemia. The study was conducted at 27 sites in four countries, including eight in Europe. Micafungin 100 mg/day or liposomal amphotericin B 3 mg/kg/day were administered once daily as a 1-hour infusion in a blinded manner. The minimum duration of therapy was 14 days. To define plasma analyte (micafungin and metabolites) concentration-time profiles, serial blood samples were collected after the first dose (Day 1), and at the end of therapy (EOT). For patients who received treatment for longer than 2 weeks, an additional profile was obtained during Week 2. To determine plasma trough analyte concentrations, blood samples were collected immediately prior to dosing on Day 2, Week 2, and EOT. In 20 evaluable, micafungin-treated patients, plasma micafungin concentrations peaked at completion of the 1-hour infusion and then declined biexponentially. Plasma concentrations of the micafungin metabolites (M-1, M-2, and M-5) remained low (<1 μg/mL) throughout the study. The mean half-life and clearance of micafungin were largely unchanged with repeated dosing up to 28 days, and no evidence of micafungin accumulation was observed. These data provide further support for the predictability of micafungin pharmacokinetics in adult patients with invasive candidiasis and candidemia.
文摘Neutropenia with fever is a special group of patients. Due to low immune function, inflammation-related clinical symptoms and signs are often not obvious, and pathogenic bacteria and infection focus are not clear. Fever may be the only sign of infection. If appropriate antimicrobial treatment is not given in time, infection-related mortality is high. In our study, we aimed to optimize the dosage regimen of Micafungin in children with febrile neutropenic against Candida spp. by Mote Carlo Simulation (MCS). Pharmacokinetic parameters and microbiological data of Micafungin were collected. Then we used MCS to calculate Probability of Target Attainment (PTA) and Cumulative Fraction of Response (CFR). With dosages of 0.5 mg/kg, 1 mg/kg, 1.5 mg/kg, 2 mg/kg, 3 mg/kg, and 4 mg/kg in oral group and dosages of 100 mg, and 200 mg in intravenous administration, all have different degree of antifungal effect. But when the dosage regimen was 50 mg IV, the therapeutic effect of Micafungin against Candida spp. was not good.
文摘目的了解新型抗真菌药物米卡芬净(micafungin,MFG)对分离自中国的念珠菌和曲霉临床株的体外抑菌活性。方法参照CLSI(Clinical and Laboratory Standards Institute,以前为NCCLS)制定的M27-A2和M38-A方案测定86株念珠菌和35株曲霉的最低抑菌浓度(MIC)或最低有效浓度(MEC)。结果MFG对大多数念珠菌属和曲霉属均有较好的抑菌作用。对念珠菌属的MIC90从高到低依次为:氟康唑(FLC)敏感的白念珠菌、热带念珠菌、光滑念珠菌为0.125μg/ml,FLC耐药和剂量依赖敏感株为0.25μg/ml,克柔念珠菌为0.5μg/ml,近平滑念珠菌8μg/ml,季也蒙念珠菌>16μg/ml。MFG对烟曲霉的MEC90为≤0.03μg/ml,对非烟曲霉的曲霉属MEC90为0.06μg/ml。MFG与唑类药物、两性霉素B(AMB)不存在交叉耐药,对FLC耐药的念珠菌、伊曲康唑耐药的曲霉、AMB不敏感的曲霉均有好的抑菌活性。结论MFG对多数念珠菌属和曲霉属(包括对唑类耐药和AMB不敏感的菌株)有较好的体外抑菌作用。
