Department of Medical Microbiology, Medical and Health Science Center, University of Debrecen, Nagyerdei Krt. 98., 4032 Debrecen, Hungary.
Mycopathologia. 2012 Oct;174(4):311-8. doi: 10.1007/s11046-012-9554-7. Epub 2012 May 8.
Caspofungin activity was determined in vitro and in vivo against three Candida orthopsilosis, three C. metapsilosis, two C. parapsilosis sensu stricto and two C. albicans isolates. MIC values and killing activity were determined in RPMI-1640 plus 50 % human serum. Neutropenic (cyclophosphamide-treated) mice were infected intravenously. Five-day intraperitoneal treatment with caspofungin was started after 24 h postinfection. Kidney burden was analyzed using the Kruskal-Wallis test with Dunn's post-test. In killing studies, caspofungin was fungistatic and fungicidal against C. albicans at ≥0.25 and ≥2 μg/ml concentrations, respectively. Caspofungin was fungistatic at ≥8-16, ≥2-8 and at ≥2-8 μg/ml against C. parapsilosis, C. orthopsilosis and C. metapsilosis, respectively. In the murine model, C. albicans was inhibited by 1, 2 and 5 mg/kg of caspofungin (P < 0.001 compared to the controls). Against C. parapsilosis, only 5 mg/kg caspofungin was effective against both isolates (P < 0.05). Two and five mg/kg of caspofungin was effective against all C. orthopsilosis and C. metapsilosis isolates (P < 0.05 to <0.001). Serum-based killing tests proved to be useful in predicting in vivo efficacy of caspofungin against four Candida species. Caspofungin at clinically attainable concentrations proved to be effective against all four species.
棘白菌素对三种近平滑念珠菌、三种中间型念珠菌、两种近平滑假丝酵母和两种白念珠菌分离株的体外和体内活性进行了测定。在 RPMI-1640 中添加 50%人血清，测定 MIC 值和杀伤活性。用环磷酰胺处理的中性粒细胞减少症小鼠经静脉感染。感染后 24 小时开始进行为期 5 天的腹腔内注射治疗。用 Kruskal-Wallis 检验和 Dunn's 事后检验分析肾脏负担。在杀伤研究中，棘白菌素对白色念珠菌的抑菌和杀菌浓度分别为≥0.25 和≥2μg/ml。棘白菌素对近平滑假丝酵母、近平滑念珠菌和中间型念珠菌的抑菌浓度分别为≥8-16、≥2-8 和≥2-8μg/ml。在小鼠模型中，1、2 和 5mg/kg 的棘白菌素抑制了白色念珠菌（与对照组相比，P<0.001）。对近平滑假丝酵母，只有 5mg/kg 的棘白菌素对两种分离株有效（P<0.05）。2 和 5mg/kg 的棘白菌素对所有的近平滑念珠菌和中间型念珠菌分离株均有效（P<0.05 至<0.001）。基于血清的杀伤试验被证明可用于预测棘白菌素对四种念珠菌的体内疗效。在临床上可达到的浓度下，棘白菌素对所有四种念珠菌均有效。
