Unidad de Microbiología Experimental, Centro de Investigación, Hospital Universitario y Politécnico La Fe, Valencia 46009, Spain.
J Antimicrob Chemother. 2013 Apr;68(4):864-8. doi: 10.1093/jac/dks489. Epub 2012 Dec 9.
Candida lusitaniae fungaemia, although infrequent (1%), is more common in immunocompromised patients than Candida albicans. Although infections produced by Candida spp. are therapeutic targets for treatment with echinocandins, little information is available regarding their killing kinetics against C. lusitaniae. The objectives of this study were to determine the killing kinetics of anidulafungin, micafungin and caspofungin against four blood isolates of C. lusitaniae by time-kill methodology.
Time-kill studies were performed in RMPI 1640 medium (5 mL, inoculum ∼10(5) cfu/mL). The number of cfu/mL was determined at 0, 2, 4, 6 and 24 h. The anidulafungin concentrations assayed were 0.03, 0.12, 0.5, 2 and 8 mg/L, while micafungin and caspofungin concentrations were 0.25, 1, 4, 16 and 32 mg/L.
MIC ranges were 0.03-1 mg/L (anidulafungin), 0.016-0.06 mg/L (micafungin) and 0.03-1 mg/L (caspofungin). The mean maximum log decrease in cfu/mL was reached with 2 mg/L anidulafungin (1.85 ± 0.4 log), 32 mg/L caspofungin (5.5 ± 0.2 log) and 32 mg/L micafungin (2.65 ± 1.9 log). Only caspofungin and micafungin reached the fungicidal endpoint (99.9% growth reduction or a 3 log decrease) with 32 mg/L at 22.8 h (caspofungin) and 26.5 h (micafungin). Analysis of variance showed significant differences in killing activity among isolates, but not among concentrations reached in serum or echinocandins.
Anidulafungin and micafungin exhibit greater killing rates than caspofungin. Caspofungin was the only echinocandin that reached the fungicidal endpoint before 24 h, but at drug concentrations (≥ 16 mg/L) not usually reached in serum. The echinocandin killing rate was isolate dependent and concentration independent.
虽然念珠菌属中卢特西亚念珠菌引起的真菌感染（1%）并不常见，但在免疫功能低下的患者中比白色念珠菌更为常见。虽然念珠菌属引起的感染是使用棘白菌素类药物治疗的靶向治疗目标，但关于其对卢特西亚念珠菌的杀菌动力学的信息很少。本研究的目的是通过时间杀菌法确定卢特西亚念珠菌的四种血液分离株对安尼度芬、米卡芬净和卡泊芬净的杀菌动力学。
在 RPMI 1640 培养基（5 mL，接种物约 10(5) cfu/mL）中进行时间杀菌研究。在 0、2、4、6 和 24 h 时测定 cfu/mL 数量。检测的安尼度芬浓度为 0.03、0.12、0.5、2 和 8 mg/L，而米卡芬净和卡泊芬净的浓度为 0.25、1、4、16 和 32 mg/L。
MIC 范围为 0.03-1 mg/L（安尼度芬）、0.016-0.06 mg/L（米卡芬净）和 0.03-1 mg/L（卡泊芬净）。以 2 mg/L 安尼度芬（1.85 ± 0.4 log）、32 mg/L 卡泊芬净（5.5 ± 0.2 log）和 32 mg/L 米卡芬净（2.65 ± 1.9 log）达到最大平均对数减少的 cfu/mL。只有卡泊芬净和米卡芬净达到杀菌终点（生长减少 99.9%或减少 3 对数），在 22.8 h（卡泊芬净）和 26.5 h（米卡芬净）时用 32 mg/L 达到。方差分析显示，分离株之间的杀菌活性存在显著差异，但血清中的药物浓度或棘白菌素类药物之间没有差异。
安尼度芬和米卡芬净的杀菌率高于卡泊芬净。卡泊芬净是唯一一种在 24 小时前达到杀菌终点的棘白菌素类药物，但在血清中通常达不到药物浓度（≥16 mg/L）。棘白菌素类药物的杀菌率与分离株有关，与浓度无关。
