Stratton VA Medical Center, Infectious Disease Research Laboratory, Albany, NY 12208, USA.
Diagn Microbiol Infect Dis. 2011 Oct;71(2):131-8. doi: 10.1016/j.diagmicrobio.2011.06.018. Epub 2011 Aug 23.
Candida glabrata (Cgl) and Candida parapsilosis (Cpa) can cause serious infections and can be resistant to some antifungal drugs. In treating infections caused by these organisms, killing rates and post-antifungal effects (PAFE) are important factors in both dose interval choice and outcome. Two strains each of Cgl and Cpa were studied. For PAFE studies, each organism was exposed to micafungin (MCF), anidulafungin (ANF), or caspofungin (CAS) for 1 h at concentrations ranging from 0.25 to 16×MIC. Cell suspensions were then washed 3 times and resuspended in fresh broth. Time 0 was immediately after resuspension of the yeast. Time-kill experiments were done using similar drug concentrations. Samples were removed at each time point (0-120 h) and viable counts determined. PAFE of ANF and CAS were generally very long, were markedly longer than those of MCF, and increased with increased drug concentration. For ANF and CAS, PAFE for Cgl were greater than those for Cpa only at 0.5 to 2 × MIC. Time-kill experiments showed that ANF, CAS, and MCF were fungicidal at 8 to 16 × MIC up to 120 h. CAS had the greatest activity against Cgl, while ANF and MCF were more active than CAS against Cpa. Because of the prolonged PAFE of these echinocandins, especially ANF and CAS, less frequent dosing during therapy of Cpa and Cgl infections could be considered. Further studies are needed to determine the clinical efficacy of longer dosing intervals.
光滑念珠菌（Cgl）和近平滑念珠菌（Cpa）可引起严重感染，并且可能对一些抗真菌药物具有耐药性。在治疗这些生物体引起的感染时，杀菌率和抗真菌后效应（PAFE）是剂量间隔选择和结果的重要因素。研究了每种念珠菌各两个菌株。对于 PAFE 研究，将每种生物体暴露于米卡芬净（MCF）、阿尼芬净（ANF）或卡泊芬净（CAS）中 1 小时，浓度范围为 0.25 至 16×MIC。然后将细胞悬浮液洗涤 3 次并重新悬浮在新鲜肉汤中。时间 0 是在重新悬浮酵母后立即进行的。使用类似的药物浓度进行杀菌实验。在每个时间点（0-120 h）取出样品并确定活菌数。ANF 和 CAS 的 PAFE 通常很长，明显长于 MCF 的 PAFE，并且随着药物浓度的增加而增加。对于 ANF 和 CAS，只有在 0.5 至 2×MIC 时，Cgl 的 PAFE 才大于 Cpa 的 PAFE。杀菌实验表明，ANF、CAS 和 MCF 在 8 至 16×MIC 时在 120 h 内具有杀菌作用。CAS 对 Cgl 的活性最大，而 ANF 和 MCF 对 Cpa 的活性大于 CAS。由于这些棘白菌素的 PAFE 延长，尤其是 ANF 和 CAS，在治疗 Cpa 和 Cgl 感染时可以考虑减少治疗期间的给药频率。需要进一步研究以确定更长的给药间隔的临床疗效。
