卡泊芬净联合伏立康唑、伊曲康唑或两性霉素B对尖端赛多孢子菌体外抑菌活性

目的 观察卡泊芬净(棘白霉素类抗真菌药)联合伏立康唑、伊曲康唑(三唑素)或两性霉素B(多烯类).作用于15株尖端赛多孢子菌的体外抑菌活性.方法 参照美国国家临床和实验室标准研究所(CLSI)的M38-A方案,药物间相互作用用分数抑菌浓度(FIC值)表示.结果 体外单独用药时,伏立康唑的MIC值的几何均数(GM)显著低于其他药物.在15株受试菌中,卡泊芬净与伊曲康唑联合时,全部菌株显示为协同作用;卡泊芬净与两性霉素B联合时,有27%的菌株显示为协同作用;卡泊芬净与伏立康唑联合时,均表现为无关作用.结论 卡泊芬净可增强伊曲康唑的体外抗真菌活性,卡泊芬净与伊曲康唑联合用药有望作为临床上治疗尖端赛多孢子菌感染的一种有效方法.     

In vitro pharmacodynamics and in vivo efficacy of fluconazole,amphotericin B and caspofungin in a murine infection by Candida lusitaniae

The in vitro activities of fluconazole (FLC), amphotericin B (AmB) and caspofungin (CSP) were evaluated against three isolates of Candida lusitaniae using time–kill curves. AmB showed in vitro fungicidal activity, whilst FLC and CSP exerted mainly strain-dependent fungistatic activity. The in vivo efficacies of the three drugs were evaluated in a murine model of disseminated infection. The doses administered were FLC 50 mg/kg/day, AmB 0.8 mg/kg/day and CSP 5 mg/kg/day. All three drugs were able to reduce the fungal burden in the kidneys of infected mice, with AmB showing the highest efficacy, followed by CSP. At least in this model, FLC, AmB and CSP are good candidates for treating invasive infections by C. lusitaniae.     

Assessing the antifungal activity, pharmacokinetics, and tissue distribution of amphotericin B following the administration of Abelcet and AmBisome in combination with caspofungin to rats infected with Aspergillus fumigatus

The purpose of this study was to assess the antifungal activity, pharmacokinetics, and tissue distribution of amphotericin B (AmpB) following the administration of Abelcet and AmBisome alone and in combination with Caspofungin to rats infected with Aspergillus fumigatus. Aspergillus fumigatus inoculum (2.1-2.5 x 10(7) colony forming units [CFU]) was injected via the jugular vein; 48 h later male albino Sprague-Dawley rats (350-400 g) were administered either a single intravenous (i.v.) dose of Abelcet (5 mg AmpB/kg; n = 6), AmBisome (5 mg AmpB/kg; n = 6), Caspofungin (3 mg/kg; n = 5), Abelcet (5 mg AmpB/kg) plus Caspofungin (3 mg/kg) (n = 6), AmBisome (5 mg AmpB/kg) plus Caspofungin (3 mg/kg) (n = 7), or physiologic saline (non-treated controls; n = 6) once daily for 4 days. Antifungal activity was assessed by organ CFU concentrations and plasma galactomannan levels. Plasma and tissue samples were taken from each animal for AmpB pharmacokinetic analysis and tissue distribution determinations. Abelcet treatment significantly decreased total fungal CFU concentrations recovered in all the organs added together by 73% compared to non-treated controls. Ambisome treatment significantly decreased total fungal CFU concentrations recovered in all the organs added together by 69% compared to non-treated controls. Caspofungin treatment significantly decreased total fungal CFU concentrations recovered in all the organs added together by 80% compared to non-treated controls. Abelcet plus Caspofungin treatment significantly decreased total fungal CFU concentrations recovered in all the organs added together by 81% compared to non-treated controls. Ambisome plus Caspofungin treatment significantly decreased total fungal CFU concentrations recovered in all the organs added together by 98% compared to non-treated controls. Abelcet treatment significantly decreased plasma galactomannan levels by 50 and 75% 96 h following the initiation of treatment in the absence and presence of Caspofungin co-therapy, respectively. AmBisome treatment significantly decreased plasma galactomannan levels by 73 and 78% 96 h following the initiation of treatment in the absence and presence of Caspofungin co-therapy, respectively. Co-administration of Caspofungin with Abelcet and AmBisome did not significantly alter the plasma concentration-time profile, pharmacokinetic parameters, and tissue distribution of AmpB. Taken together, our findings suggest that an alternative mechanism, possibly at the cellular level rather than altered AmpB disposition, may be an explanation for the differences in organ CFU concentrations following Abelcet plus Caspofungin versus AmBisome plus Caspofungin administration.     

Activity of voriconazole, itraconazole, fluconazole and amphotericin B in vitro against 1763 yeasts from 472 patients in the voriconazole phase III clinical studies

The susceptibility of 1763 yeast isolates (from 22 species and seven genera) was tested using Clinical and Laboratory Standards Institute M27-A2 microdilution methodology. Candida spp. predominated (97.1%), mainly C. albicans (51.4%), C. glabrata (16.4%) and C. tropicalis (13.7%), followed by Trichosporon spp. (1.1%) and Cryptococcus neoformans (1.0%). Most isolates came from blood/catheters (72.0%) or the oesophagus/oropharynx (11.3%). The voriconazole, itraconazole, fluconazole and amphotericin B MIC90 values (minimum inhibitory concentration for 90% of the isolates) for all isolates were 1.0, 2.0, 64 and 1.0 microg/mL, respectively. Voriconazole MICs correlated with those for fluconazole (r = 0.91) and itraconazole (r = 0.90). Only 109 isolates (6.2%) had voriconazole MICs > or = 4.0 microg/mL; all were C. albicans, C. glabrata or C. tropicalis resistant to itraconazole (and most to fluconazole). Isolates from 22 patients with amphotericin MICs > or = 2.0 microg/mL (range 2.0-16.0 microg/mL) were also cross-resistant to one or more of the triazoles. Patients (n = 34) with voriconazole-resistant isolates showed a 56% response to voriconazole therapy, and those patients (n = 261) with susceptible isolates showed a 71% response. Twenty-three voriconazole-treated patients had baseline resistant isolates, in eight patients voriconazole resistance developed during therapy and in three patients a different resistant species arose during therapy. Thus, voriconazole MICs correlate with those of fluconazole and itraconazole and may predict clinical outcome.