JMI Laboratories, North Liberty, Iowa, USA; University of Iowa, Iowa City, Iowa, USA.
JMI Laboratories, North Liberty, Iowa, USA.
Int J Antimicrob Agents. 2017 Sep;50(3):352-358. doi: 10.1016/j.ijantimicag.2017.03.028. Epub 2017 Jul 6.
CD101 is a novel echinocandin with exceptional chemical stability and long-acting pharmacokinetics. The activity of CD101 and comparators was evaluated using CLSI broth microdilution methods against 713 invasive fungal isolates, including 589 Candida spp. (6 species), 14 C. neoformans, 97 A. fumigatus and 13 A. flavus species complex collected worldwide during 2015. All C. tropicalis, C. krusei and C. dubliniensis, 99.7% of C. albicans and 98.3% of C. glabrata were inhibited by ≤0.12 µg/mL of CD101, and these isolates were susceptible/wild type to other echinocandins using CLSI clinical breakpoint and epidemiological cutoff value (ECV) interpretive criteria. C. parapsilosis displayed higher MIC values (range 0.25-2 µg/mL), but similar results were observed for other echinocandins. One C. glabrata and one C. albicans with CD101 MIC value at 1 and 0.25 µg/mL possessed F625S and S645P alterations on FKS1, respectively. These isolates also displayed elevated MIC values for at least one clinically available echinocandin. Fluconazole resistance was noted for 6.6% of C. glabrata and 3.6% C. parapsilosis. Echinocandins had limited activity against C. neoformans. CD101 activity against A. fumigatus and A. flavus (MEC ≤0.03 µg/mL) was comparable to other echinocandins (MEC ≤0.03 µg/mL). These moulds had MIC values below ECVs for the mould-active azoles. CD101 was as active as other echinocandins against common fungal organisms recovered from invasive fungal infections. The extended half-life profile is very desirable as less frequent dosing of this agent should facilitate shorter and more cost-effective hospital stays, improve compliance for outpatients, and provide more convenient outpatient prophylaxis.
CD101 是一种新型棘白菌素,具有出色的化学稳定性和长效药代动力学特性。采用 CLSI 肉汤微量稀释法,对 713 株侵袭性真菌分离株(包括 589 株念珠菌属(6 种)、14 株新型隐球菌、97 株烟曲霉和 13 株黄曲霉种复合体)进行了 CD101 及对照药物的活性评估。所有热带念珠菌、克柔念珠菌和都柏林念珠菌、99.7%白念珠菌和 98.3%光滑念珠菌对 CD101 的抑制浓度均≤0.12µg/mL,根据 CLSI 临床折点和流行病学折点(ECV)解释标准,这些分离株对其他棘白菌素敏感/野生型。近平滑念珠菌的 MIC 值较高(范围为 0.25-2µg/mL),但其他棘白菌素也观察到类似结果。一株 CD101 MIC 值为 1µg/mL 的光滑念珠菌和一株 CD101 MIC 值为 0.25µg/mL 的白念珠菌的 FKS1 上分别存在 F625S 和 S645P 改变。这些分离株对至少一种临床可用的棘白菌素也表现出升高的 MIC 值。6.6%的光滑念珠菌和 3.6%的近平滑念珠菌对氟康唑耐药。棘白菌素对新型隐球菌的活性有限。CD101 对烟曲霉和黄曲霉(MEC≤0.03µg/mL)的活性与其他棘白菌素(MEC≤0.03µg/mL)相当。这些真菌的 MIC 值低于唑类药物的 ECV。CD101 对常见的从侵袭性真菌感染中分离到的真菌具有与其他棘白菌素相当的活性。半衰期延长的特点非常理想,因为这种药物的给药频率降低,应能缩短和降低治疗成本,提高门诊患者的依从性,并提供更方便的门诊预防。