Predictive value of minimal fungicidal concentration (MFC) of amphotericin B (AMB) in deep-seated infections caused by Candida krusei

Abstract

Póster presentado en 43rd Annual Interscience Conference on Antimicrobial Agents and Chemotherapy September 14 - 17, 2003; Chicago, IllinoisBackground: It has been reported that AMB MFCs have a wider range and could be better predictors of clinical outcome than MICs in the setting of non-Candida albicans infections. Methods: A 62-year old male patient with acute myeloblastic leukemia, receiving fluconazole prophylaxis, during remission induction chemotherapy developed C. krusei fungemia (CK-18). antifungal therapy consisted on liposomal AMB (3 mg/kg/day) for two weeks followed by standard-dose caspofungin for 4 weeks and then he received, after discharge, itraconazole 200 mg bid for 4 weeks. Four months later, he developed a septic spondilodiscitis and C. krusei (CK-19) was isolated at infection site by fine-needle aspiration. Because of high AMB MFCs, on this occasion a combination of caspofungin and voriconazole, at standard doses, was given for six weeks with favorable clinical response. MICs (100% growth inhibition) were determinated by NCCLS M27-A2, colorimetric, & Etest methods). For MFC, the content of each clear MIC well (0.2 ml) was subcultured onto two Sabouraud dextrose agar plates. Strain characterization was performed by PCR amplification and subsequent restriction analysis of the ribosomal region spanning the internal transcribed spacers (ITS1 and ITS2), the 5.8S rRNA gene and the sequencing of the D1/D2 regions of the 26S rRNA gene. Results: PCR proved that both strains were C. krusei and the mtDNA restriction analysis and specific PCR of d sequences that they were different strains. AMB MICs (mg/l) for CK-18/CK-19 by M27-A2, Etest and colorimetric methods were: 1, 0.5, 1 / 1, 0.75, 1, respectively and AMB MFCs (mg/l): >16-16. Conclusions: AMB MFCs values for both C. krusei were substantially higher than MICs and could be better predictors of therapeutic failure with AMB and in vitro resistance

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