Emily K Adams1, Deborah S Ashcraft1, George A Pankey2. 1. Department of Infectious Disease Translational Research, Ochsner Clinic Foundation, New Orleans, Louisiana. 2. Department of Infectious Disease Translational Research, Ochsner Clinic Foundation, New Orleans, Louisiana. Electronic address: gpankey@ochsner.org.
Abstract
BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: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.