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In vitro resistance to amphotericin B and caspofungin in clinical isolates of C. glabrata were confirmed in a mouse model

Abstract number: o428

Krogh-Madsen  M., Arendrup  M.C., Heslet  L., Knudsen  J.D.

Objectives: 

Candida glabrata isolates from an ICU patient were found to be resistant to amphotericin B and/or caspofungin in-vitro. Three clinical C. glabrata isolates were studied in a mouse model.

Methods: 

The MICs were determined for four C. glabrata strains by two microdilution methods, CLSI and EUCAST using RPMI and AM3, and by E-tests. Time-kill curves were done for both drugs and both media. Outbreed NMRI mice were challenged i.v., and treated i.p. in groups of six, once daily for 3 days with amphotericin B (6 mg/kg/day), caspofungin (5 mg/kg/day), or saline. The mice were sacrificed on day five, kidneys were removed, homogenized in saline, and the cfu's were determined. The differences between cfu's (control versus treated mice) were used as effect parameter, and a p-value of < 0.05 was considered significant.

Results: 

For amphotericin B, the E-tests for the four strains resulted in higher MIC-values (1.5, 6–8, 8–12, > 32 mg/mL), when compared to the broth microdilution methods (0.5, 1, 1–2, 2–4 mg/mL), respectively. Both microdilution methods and the different media separated the amphotericin B susceptible and the amphotericin B resistant isolates poorly, but caspofungin susceptible from resistant isolates were separated quit clearly. In the mouse model, the strains with amphotericin B E-tests of > 32, 6–8, and 1.5 mg/mL, were found to be resistant, intermediate susceptible and susceptible, respectively. In the mouse model, the susceptibility/resistances to caspofungin were confirmed.

Conclusion: 

Amphotericin B resistance in isolates of C. glabrata of possible clinical significance can be determined using E-test, but easily be overlooked in the microdilution methods. Resistance to amphotericin B determined by the E-test was confirmed in the mouse model. The susceptibilities determined in-vitro to Caspofungin in isolates of C. glabrata was confirmed in a mouse model.

Session Details

Date: 01/08/2007
Time: 00:00-00:00
Session name: XXIst ISTH Congress
Subject:
Location: Oxford, UK
Presentation type:
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