In Vitro Synergy of Polymyxin B and Fluconazole against Candida glabrata

Ref ID: 18793

Author:

G. A. Pankey, MD – Director, Infectious Disease Research1, D. S. Ashcraft, BS MT – Supervisor, Infectious Disease Research Laboratory 2;

Author address:

1Ochsner Clinic Fndn., New Orleans, LA, 2Ochsner Clinic foundation, New Orleans, LA.

Full conference title:

52nd Annual ICAAC

Date: 9 September 2014

Abstract:

Background: Polymyxin B, a last resort antibiotic used to treat multi-drug resistant Gram-negative bacterial infections, is also known to possess in vitro fungicidal activity. A previous study by Zhai et al., 2010, showed synergy with a disk diffusion method when polymyxin B (PB) was combined with fluconazole (FLC) against a single strain of C. glabrata. Antifungal resistant C. glabrata is problematic, so we decided to do synergy testing with our recent C. glabrata bloodstream infection isolates also using this combination. Methods: Thirty-seven C. glabrata bloodstream infection isolates were collected 2009-2011 from individual patients. Isolates were identified using the API 20C yeast identification system. Testing was performed using a modified bacterial Etest synergy method (AAC, 49:2959-2964, 2005). Etest MICs were determined in triplicate (mean value used) following manufacturer’s guidelines for Candida. Recently revised CLSI breakpoints used for interpretation of FLC MICs (µg/ml) were: < 32 S-dose dependent; > 64 R. There are no CLSI interpretive guidelines for testing PB against C. glabrata. The Etest MIC: MIC synergy method was performed in triplicate (mean value calculated) using concentrations of ½ MIC PB + 1 x MIC FLC. Results were read at 24 and 48 h. To evaluate the effect of the combination, the fractional inhibitory concentration (FIC) was calculated for each antibiotic. Synergy was defined by a 8721;FIC < 0.5; indifference, >0.5 – 4; antagonism, >4. Results: Etest MICs (µg/ml) were: FLC, 12 to > 256 (77% S-dose dependent; 23% R). Eight of the 11 FLC-resistant strains were identified at 24 h. PB MICs (µg/ml) were 64 – > 1024. Overall, Etest synergy testing showed 26/37 (70%) synergy, including 9/11 (82%) FLC-R strains. Overall, 11/37 (30%) were indifferent. No antagonism was detected. Conclusions: In vitro synergy with polymyxin B and fluconazole was demonstrated in 26/37 (70%) bloodstream infection isolates of C. glabrata, including 9/11 (82%) fluconazole-resistant strains. Further synergy studies with additional C. glabrata isolates are needed since polymyxin B + fluconazole may be given to seriously ill patients suspected of polymicrobic infection.

Abstract Number: M-1717

Conference Poster: y

Conference Year: 2012

Link to conference website: NULL

New link: NULL

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