We evaluated the in vitro activity of the new echinocandin antifungal micafungin against Candida spp. using microdilution and time-kill methods. Additionally, we examined the postantifungal effect (PAFE) of micafungin. Finally, we evaluated the effect of the addition of serum and plasma on the MIC of micafungin. Four Candida albicans isolates and two isolates of each Candida glabrata, Candida krusei, and Candida tropicalis were selected for testing. The MICs of micafungin were determined in RPMI 1640 medium buffered with morpholinepropanesulfonic acid alone and with the addition of 10, 20, and 50% human serum and plasma. MICs were determined by using two endpoints: a prominent reduction in growth (the MIC at which 80% of isolates are inhibited [MIC 80 ]) and complete visual inhibition of growth (MIC 100 ). The minimum fungicidal concentration (MFC) of micafungin for each isolate was also determined. Time-kill curves were determined for each isolate in RPMI 1640 medium with micafungin at concentrations ranging from 0.125 to 16 times the MIC 80 to assess the correlation between MIC 80 and fungicidal activity. PAFE studies were conducted with each isolate by using concentrations ranging between 0.25 and 4 times the MIC 80 . The MIC 80 s for the test isolates ranged from 0.0039 to 0.25 g/ml. Overall, the addition of serum or plasma increased the MIC 6 to 7 doubling dilutions for C. albicans and 3 to 4 doubling dilutions for C. krusei and C. tropicalis. Micafungin time-kill studies demonstrated fungicidal activity at concentrations ranging from 4 to 16 times the MIC 80 . Micafungin is very potent agent against a variety of Candida spp., producing fungicidal activity against 7 of 10 isolates tested. A PAFE was observed against all isolates. The PAFE was influenced by the drug concentration, with the highest concentration resulting in the longest observed PAFE in each case. The highest concentration tested, four times the MIC, resulted in a PAFE of more than 9.8 h for 5 of 10 isolates tested (range, 0.9 to >20.1 h).Micafungin is an investigational antifungal agent that was first isolated from the culture broth of Coleophoma empedri. It is a novel water-soluble lipopeptide derived by semisynthetic modification of FR901379, a naturally occurring cyclic hexapeptide with a fatty acyl side chain, and is similar in structure to the echinocandins and pneumocandins. Micafungin has inhibitory activity against ␤-1,3-glucan synthase (T. Iwamoto, N. Sakamoto, M. Yamashita, M. Ezaki, S. Hashimoto, T. Furuta, M. Okuhara, and M. Kohsaka, Progam Abstr. 33rd Intersci. Conf. Antimicrob. Agents Chemother., abstr. 371, 1993) and has been shown to exhibit potent in vitro activity against Candida and Aspergillus species

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Amphotericin B, flucytosine, fluconazole, and voriconazole alone and in combination were evaluated against isolates of Candida lusitaniae. MICs were determined by broth microdilution and Etest, and time-kill studies were conducted. Amphotericin B resulted in fungicidal activity against most isolates, whereas fluconazole, voriconazole, and flucytosine produced primarily fungistatic activities. The addition of flucytosine to amphotericin B resulted in a faster rate and greater extent of kill for isolates for which the MICs of amphotericin B were elevated.Candida lusitaniae was first isolated from the digestive tracts of warm-blooded animals. C. lusitaniae is rarely an opportunistic human pathogen; however, when implicated it often causes serious and fatal disease (1). Despite its low prevalence, C. lusitaniae is classified as an emerging opportunistic pathogen (3). A hallmark of C. lusitaniae is its innate resistance or rapid development of resistance to amphotericin B (4). Pfaller and colleagues demonstrated the ability of a single strain to develop resistance to amphotericin B rapidly during antifungal therapy (8).As a result of the perceived high level of resistance of C. lusitaniae to amphotericin B and the relative lack of information on this topic, we evaluated the antifungal activities of amphotericin B, fluconazole, voriconazole, and flucytosine alone and in combination against C. lusitaniae.Antifungal agents. Amphotericin B (Sigma Chemical Company, St. Louis, Mo.), flucytosine (Sigma), fluconazole (Pfizer, Inc., New York, N.Y.), and voriconazole (Pfizer) were utilized for susceptibility and time-kill procedures. A stock solution of each antifungal agent was prepared utilizing RPMI 1640 medium (Sigma) buffered to pH 7.0 with 0.165 M morpholinepropanesulfonic acid (MOPS) buffer (Sigma) as the diluent. Dimethyl sulfoxide (DMSO) was used to aid the solubilization of amphotericin B and voriconazole. The final concentration of DMSO was such that its concentration in the test solutions comprised less than 1% of the total solution composition. Growth curves were conducted with DMSO at concentrations equal to those present in the test solutions to verify the lack of an inhibitory effect on the growth of the test isolates. Stock solutions were stored at Ϫ70°C until needed for testing.Test isolates. Eleven clinical isolates of C. lusitaniae were obtained for testing. Antifungal susceptibility testing. The MICs of amphotericin B, flucytosine, fluconazole, and voriconazole for each test isolate were determined by broth microdilution according to the methods approved by the National Committee for Clinical Laboratory Standards (M27-A) and by Etest according to the manufacturer's specifications (AB Biodisk, Solna, Sweden) (7). MICs of voriconazole were not determined by Etest.Time-kill curve procedures. Time-kill procedures were conducted as described previously (2, 5). Fungi were obtained from stored samples and subcultured twice on potato dextrose agar plates (Remel) prior to testing. Fungal suspensions were prepared i...

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