Global Surveillance of In Vitro Activity of Micafungin against
            <i>Candida</i>
            : a Comparison with Caspofungin by CLSI-Recommended Methods

Pfaller, Michael A.; Boyken, L.; Hollis, Richard J.; Messer, S. A.; Tendolkar, S.; Diekema, Daniel J.

doi:10.1128/jcm.00872-06

Cited by 84 publications

(75 citation statements)

References 17 publications

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“…Nevertheless, 95.1% of C. guilliermondii, 99.9% of C. parapsilosis, and 100% of C. krusei isolates were inhibited by Յ2 g/ml of caspofungin, a concentration that is attained throughout the dosing interval at standard doses (70-mg loading dose and 50-mg daily dose) of caspofungin (8). As noted previously (50,51,54), 100% of fluconazole-resistant isolates of Candida spp. were inhibited by Յ2 g/ml (MIC 90 , 0.25 g/ml) of caspofungin ( Table 2).…”

Section: Resultsmentioning

confidence: 88%

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Correlation of MIC with Outcome for Candida Species Tested against Caspofungin, Anidulafungin, and Micafungin: Analysis and Proposal for Interpretive MIC Breakpoints

et al. 2008

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The CLSI Antifungal Subcommittee followed the M23-A2 "blueprint" to develop interpretive MIC breakpoints for anidulafungin, caspofungin, and micafungin against Candida species. MICs of <2 g/ml for all three echinocandins encompass 98.8 to 100% of all clinical isolates of Candida spp. without bisecting any species group and represent a concentration that is easily maintained throughout the dosing period. Data from phase III clinical trials demonstrate that the standard dosing regimens for each of these agents may be used to treat infections due to Candida spp. for which MICs are as high as 2 g/ml. An MIC predictive of resistance to these agents cannot be defined based on the data from clinical trials due to the paucity of isolates for which MICs exceed 2 g/ml. The clinical data set included only three isolates from patients treated with an echinocandin (caspofungin) for which the MICs were >2 g/ml (two C. parapsilosis isolates at 4 g/ml and one C. rugosa isolate at 8 g/ml). Based on these data, the CLSI subcommittee has decided to recommend a "susceptible only" breakpoint MIC of <2 g/ml due to the lack of echinocandin resistance in the population of Candida isolates thus far. Isolates for which MICs exceed 2 g/ml should be designated "nonsusceptible" (NS). For strains yielding results suggestive of an NS category, the organism identification and antimicrobial-susceptibility test results should be confirmed. Subsequently, the isolates should be submitted to a reference laboratory that will confirm the results by using a CLSI reference dilution method.

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Section: Resultsmentioning

confidence: 88%

“…There is broad experience with testing the echinocandins by using the CLSI BMD method (24,42,50,51,55,(58)(59)(60). In addition to standardized testing methods, the CLSI Antifungal Subcommittee has approved quality control limits for BMD test methods with all three echinocandins (11,12).…”

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confidence: 99%

Correlation of MIC with Outcome for Candida Species Tested against Caspofungin, Anidulafungin, and Micafungin: Analysis and Proposal for Interpretive MIC Breakpoints

et al. 2008

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“…Large-scale surveillance studies have documented the outstanding potency of echinocandin drugs against clinical isolates of Candida species in routine susceptibility assays (EspinelIngroff, 2003;Pfaller et al, 2003b;Pfaller et al, 2005a;Pfaller et al, 2006). These studies also reveal the presence of occasional strains from highly susceptible species that display uncharacteristically high MIC values.…”

Section: Elevated Mic and Clinical Outcomementioning

confidence: 99%

“…Surveillance studies have shown that some Candida spp., such as C. parapsilosis and C. guilliermondii, display higher echinocandin antifungal MIC values (MIC 0.5-8 μg/ml) relative to other Candida species (Espinel-Ingroff, 2003;Pfaller et al, 2003a;Pfaller et al, 2006). The clinical significance of this intrinsic reduced susceptibility is unclear since patients with these infecting strains can be successfully treated with echinocandin drugs at standard dosages (Mora-Duarte et al, 2002;Bennett, 2006).…”

Section: Amino Acid Polymorphisms In Fks1 Account For Intrinsic Reducmentioning

confidence: 99%

Resistance to echinocandin-class antifungal drugs

Perlin¹

2007

Drug Resistance Updates

455

400

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Invasive fungal infections cause morbidity and mortality in severely ill patients, and limited drug classes restrict treatment choices. The echinocandins drugs are the first new class of antifungal compounds that target the fungal cell wall by blocking β-1,3-D-glucan synthase. Elevated MIC values with occasional treatment failure have been reported for strains of Candida. Yet, an uncertain correlation exists between clinical failure and elevated MIC values for the echinocandin drugs. Fungi display several adaptive physiological mechanisms that result in elevated MIC values. However, resistance to echinocandin drugs among clinical isolates is associated with amino acid substitutions in two "hot-spot" regions of Fks1, the major subunit of glucan synthase. The mutations, yielding highly elevated MIC values, are genetically dominant and confer cross-resistance to all echinocandin drugs. Prominent Fks1 mutations decrease the sensitivity of glucan synthase for drug by one thousand-fold or more, and strains harboring such mutations may require a concomitant increase in drug to reduce fungal organ burdens in animal infection models. The Fks1-mediated resistance mechanism is conserved in a wide variety of Candida spp. and can account for intrinsic reduced susceptibility of certain species. Fks1 mutations confer resistance in both yeasts and moulds suggesting that this mechanism is pervasive in the fungal kingdom.

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“…The in vitro assay (in triplicate) was performed using the broth microdilu- tion method according to the recommendations of the NCCLS 38 and Pfaller et al 39 The MIC was considered the lowest peptide concentration that showed no increase in turbidity after overnight incubation at 37°C.…”

Section: Antifungal Assaymentioning

confidence: 99%

Synthesis and antimicrobial activity of dermaseptin S1 analogues

Savoia

Guerrini

Marzola

et al. 2008

Bioorganic & Medicinal Chemistry

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a b s t r a c tDermaseptins are peptides found in the skin secretions of Phyllomedusinae frogs. These peptides exert lytic action on some microorganisms without substantial haemolysis. In an attempt to understand the antimicrobial activity of these peptides we designed several dermaseptin S1 (ALWKTMLKKLGTMALHAG-KAALGAAADTISQGTQ) (DS1) analogues. All peptides were tested on the growth of prokaryotic (Grampositive and Gram-negative bacteria) and eukaryotic (the yeast Candida albicans and the protozoon Leishmania major) organisms. Our data showed a dose-dependent killing effect by most DS1 derivatives. Maximal antibacterial activity was displayed by a 16-mer peptide that was more active than native DS1.

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Global Surveillance of In Vitro Activity of Micafungin against Candida : a Comparison with Caspofungin by CLSI-Recommended Methods

Cited by 84 publications

References 17 publications

Correlation of MIC with Outcome for Candida Species Tested against Caspofungin, Anidulafungin, and Micafungin: Analysis and Proposal for Interpretive MIC Breakpoints

Correlation of MIC with Outcome for Candida Species Tested against Caspofungin, Anidulafungin, and Micafungin: Analysis and Proposal for Interpretive MIC Breakpoints

Resistance to echinocandin-class antifungal drugs

Synthesis and antimicrobial activity of dermaseptin S1 analogues

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