Adams Emily K, Ashcraft Deborah S, Pankey George A
Department of Infectious Disease Translational Research, Ochsner Clinic Foundation, New Orleans, Louisiana.
Department of Infectious Disease Translational Research, Ochsner Clinic Foundation, New Orleans, Louisiana.
Am J Med Sci. 2016 Mar;351(3):265-70. doi: 10.1016/j.amjms.2015.12.014.
Candida species account for most invasive fungal infections, and the emergence of fluconazole and caspofungin resistance is problematic. Overcoming resistance with synergism between 2 drugs may be useful. In a 2013 in vitro study, caspofungin plus colistin (polymyxin E) was found to act synergistically against fluconazole-resistant and susceptible Candida albicans isolates. The purpose of our study was to extend this finding by evaluating caspofungin plus polymyxin B for in vitro synergy against fluconazole-resistant Candida glabrata isolates.
A total of 7 fluconazole-resistant C. glabrata bloodstream infection isolates were obtained from 2010-2011. Of these, 2 isolates were also resistant to caspofungin. Minimum inhibitory concentrations (MICs) for caspofungin and polymyxin B were determined by Etest and broth microdilution. Clinical and Laboratory Standards Institute breakpoints were used for fluconazole and caspofungin MIC interpretations. No interpretive guidelines exist for testing polymyxin B against C. glabrata. Synergy testing with caspofungin (1 × MIC) and polymyxin B (½MIC) was performed using a modified bacterial Etest synergy method and time-kill assay.
With the Etest synergy method, 4 out of 7 isolates showed in vitro synergy and 1 out of 7 showed additivity. The remaining isolates (both caspofungin resistant) showed indifference. Using the time-kill assay, 1 out of 7 isolates showed synergy, 1 showed additivity and the remaining 5 (including both caspofungin-resistant isolates) showed indifference.
Caspofungin susceptibility may be required for synergism between caspofungin and polymyxin B. Further synergy testing with caspofungin plus polymyxin B and additional fluconazole-resistant C. glabrata isolates should be performed. In vitro synergy/additivity may or may not correlate with in vivo benefit.
念珠菌属是大多数侵袭性真菌感染的病因，氟康唑和卡泊芬净耐药性的出现是个问题。利用两种药物之间的协同作用克服耐药性可能会有帮助。在2013年的一项体外研究中，发现卡泊芬净加黏菌素（多黏菌素E）对氟康唑耐药和敏感的白色念珠菌分离株具有协同作用。我们研究的目的是通过评估卡泊芬净加多黏菌素B对氟康唑耐药的光滑念珠菌分离株的体外协同作用来扩展这一发现。
从2010年至2011年共获得7株氟康唑耐药的光滑念珠菌血流感染分离株。其中，2株对卡泊芬净也耐药。采用Etest法和肉汤微量稀释法测定卡泊芬净和多黏菌素B的最低抑菌浓度（MIC）。临床和实验室标准协会的断点用于氟康唑和卡泊芬净MIC的解释。目前尚无针对光滑念珠菌检测多黏菌素B的解释性指南。使用改良的细菌Etest协同方法和时间杀菌试验对卡泊芬净（1×MIC）和多黏菌素B（½MIC）进行协同试验。
采用Etest协同方法，7株分离株中有4株显示体外协同作用，7株中有1株显示相加作用。其余分离株（均对卡泊芬净耐药）显示无协同作用。采用时间杀菌试验，7株分离株中有1株显示协同作用，1株显示相加作用，其余5株（包括2株对卡泊芬净耐药的分离株）显示无协同作用。
卡泊芬净和多黏菌素B之间的协同作用可能需要卡泊芬净敏感。应进一步对卡泊芬净加多黏菌素B和更多氟康唑耐药的光滑念珠菌分离株进行协同试验。体外协同/相加作用可能与体内疗效相关，也可能不相关。
