The Post-Antifungal Effect (PAFE) of Caspofungin.



Background: The post-antibiotic effect - or post-antifungal effect in the case of antifungals - is defined as the delay of growth of microorganisms after a limited period of exposure to an antibiotic and subsequent removal of the drug. The PAE index is the time needed for the cell count to increase by a factor of 1 log in comparison to an untreated control culture. The PAE is a pharmacodynamic factor which may have implications for dosage regimens. The purpose of our study was to determine the PAFE for the newly introduced echinocandin Caspofungin against clinical isolates of Candida albicans. Methods: The MIC of Caspofungin against 9 C.albicans were determined using broth microdilution methods according to NCCLS recommendations. For calculation of the PAFE all strains were exposed to the 0,5-; 1-; 2-; 4-, 8-, 16-, 32-fold MIC concentration for 120 min in a shaking water bath at 37°C. The drug was removed by centrifugation and resuspending the pellett in antimycotic free RPMI 1640 medium. Then, BD BACTEC mycosis blood culture bottles were inoculated with 100 µl of the fungal suspension and incubated in the BACTEC 9420 system. The PAFE index is calculated by subtracting the time when exponential growth of the drug-exposed test strain is signaled from that of the non-exposed control strain. Results: MIC values were between 0.05 and 2 µg/ml. The PAFE indices showed a great variation ranging from 0 to 180 min (1-fold MIC) and from 180 to 500 min (32-fold MIC). With the exception of one highly susceptible strain (MIC 0.05 µg/ml) there was no direct correlation between the individual MIC values and the PAFE index. Conclusions: In contrast to relatively uniform PAE indices of bacteria in the presence of specific antibiotics, our data show a wide variation of the PAFE index for C.albicans and Caspofungin, which may reflect strain-dependent variations similar to the results found in kill-kinetic studies.

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42nd Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 42nd