Micafungin activity against Candida albicans with diverse azole resistance phenotypes

Richards, Theresa S.; Oliver, Brian G.; White, Theodore C.

doi:10.1093/jac/dkn156

Cited by 20 publications

(15 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These results of in vitro activity match published data by other authors for Candida and Aspergillus species (5,6,8,9,21), including the good activities of the three echinocandins against azole-resistant isolates (15,16). There again, this study collects susceptibility data on species of fungal pathogens that have not been published before, such as non-Candida Ascomycota yeasts and some species of hyaline and black molds.…”

supporting

confidence: 86%

Activity Profile In Vitro of Micafungin against Spanish Clinical Isolates of Common and Emerging Species of Yeasts and Molds

Cuenca‐Estrella

Gómez-López

Mellado

et al. 2009

Antimicrob Agents Chemother

View full text Add to dashboard Cite

A collection of 2,278 isolates belonging to 86 different fungal species was tested with micafungin and eight other drugs using the EUCAST procedures. Micafungin was active against species of Candida and Aspergillus (even azole-resistant species) as well as Penicillium spp., Scedosporium apiospermum, and Acremonium spp. It was inactive for species of Basidiomycota and Mucorales and for multiresistant species such as those of Fusarium.Micafungin is a new drug that belongs to the echinocandin class of antifungal agents. Its mechanism of action is by means of the inhibition of 1,3-␤-D-glucan synthesis in the fungal cell wall (10).Micafungin has been recently approved in Europe and the United States for the treatment of candidemia, acute disseminated candidiasis, Candida peritonitis and abscesses, esophageal candidiasis, and recently for the prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation.The in vitro activity of micafungin against most common species of Candida is well known (4, 11-13). However, information is limited for uncommon species of yeasts as well as for molds.The aim of this study is to analyze the in vitro activity of micafungin and eight other antifungal agents against a collection of clinical isolates of yeasts and molds from human beings using the methods approved by AFST-EUCAST.The strains were recovered from 115 Spanish hospitals through a period of 3 years, from 2005 to 2007. A total of 2,278 clinical isolates were included in the analysis. Isolates were identified by morphological and biochemical methods and sequencing of DNA targets if necessary. They belonged to 86 different species of common and emerging fungal pathogens. The isolates were obtained from blood (559; 24.5%), biopsies and other deep sites (217; 9.5%), respiratory tract specimens (751; 33%), skin samples (180; 7.9%), and other locations (707; 25.1%).The following drugs were used: amphotericin B (range, 16.0 to 0.03 g/ml; Sigma-Aldrich Quimica S.A., Madrid, Spain), flucytosine (64.0 to 0.12 g/ml; Sigma-Aldrich), fluconazole (64.0 to 0.12 g/ml; Pfizer S.A. Madrid, Spain), itraconazole (8.0 to 0.015 g/ml; Janssen S.A., Madrid, Spain), voriconazole (8.0 to 0.015 g/ml; Pfizer S.A.), posaconazole (8.0 to 0.015

show abstract

supporting

confidence: 86%

Activity Profile In Vitro of Micafungin against Spanish Clinical Isolates of Common and Emerging Species of Yeasts and Molds

Cuenca‐Estrella

Gómez-López

Mellado

et al. 2009

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…For each pair one was FLC-susceptible and the other a FLC-resistant daughter strain ( Fig 3 ). The azole resistance of FR2 is primarily CaMdr1p dependent [ 29 ] whereas the azole resistance of FHB3 is CaCdr1p/CaCdr2p dependent [ 35 ]. The peptide derivative RC21v3 [ 18 ] was used as a positive control for CaCdr1p-specific chemosensitization.…”

Section: Resultsmentioning

confidence: 99%

Inhibitors of the Candida albicans Major Facilitator Superfamily Transporter Mdr1p Responsible for Fluconazole Resistance

Keniya

Fleischer²,

Klinger³

et al. 2015

PLoS ONE

View full text Add to dashboard Cite

ObjectiveTo identify a novel class of inhibitors of fungal transporters involved in drug resistance.MethodsA series of structurally-related low molecular mass compounds was synthesized using combinatorial chemistry of a cyclobutene-dione (squarile) core. These compounds were screened for their inhibition of plasma membrane Major Facilitator Superfamily (MFS) and ATP-binding cassette (ABC) transporters responsible for efflux pump-mediated drug resistance in the fungal pathogen Candida albicans. Strains of Saccharomyces cerevisiae that specifically overexpress the MFS pump CaMdr1p or the ABC transporter CaCdr1p were used in primary screens and counterscreens, respectively, and to detect inhibition of glucose-dependent Nile Red efflux. Efflux pump inhibition, activity as pump substrates and antifungal activity against yeast and clinical isolates expressing efflux pumps were determined using agarose diffusion susceptibility assays and checkerboard liquid chemosensitization assays with fluconazole.ResultsThe screen identified five structurally-related compounds which inhibited CaMdr1p. Two compounds, A and B, specifically chemosensitized AD/CaMDR1 to FLC in a pH-dependent fashion and acted synergistically with FLC in checkerboard liquid MIC assays but compound B had limited solubility. Compound A chemosensitized to FLC the azole-resistant C. albicans strain FR2, which over-expresses CaMdr1p, inhibited Nile Red efflux mediated by CaMdr1p but not CaCdr1p and was not toxic to cultured human cells. A minor growth-inhibitory effect of B on AD/CaMDR1, but not on AD/CaCDR1 and AD/CaCDR2, indicated that compound B may be a substrate of these transporters. The related compound F was found to have antifungal activity against the three pump over-expressing strains used in the study.ConclusionsCompound A is a ‘first in class’ small molecule inhibitor of MFS efflux pump CaMdr1p.

show abstract

“…Micafungin has shown its possible efficacy and safety as empirical therapy for febrile neutropenic patients in non-randomized studies [ 10 – 13 ]. In addition, micafungin may have an advantage over azole-resistant Candida and Aspergillus species [ 14 , 15 ]. In Korea, itraconazole has been the only drug approved for empirical antifungal therapy since 2005 despite increasing demands for new antifungal empirical therapy.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of micafungin versus intravenous itraconazole as empirical antifungal therapy for febrile neutropenic patients with hematological malignancies: a randomized, controlled, prospective, multicenter study

et al. 2015

View full text Add to dashboard Cite

Micafungin, a clinically important echinocandin antifungal drug, needs to be investigated as empirical therapy in febrile neutropenia in comparison with azole compounds. A prospective randomized study was conducted to compare clinical outcomes between micafungin and intravenous itraconazole as an empirical therapy for febrile neutropenia in hematological malignancies. The antifungal drug (micafungin 100 mg or itraconazole 200 mg IV once daily) was given for high fever that was sustained despite the administration of appropriate antibiotics. Treatment success was determined by composite end points based on breakthrough invasive fungal infection (IFI), survival, premature discontinuation, defervescence, and treatment of baseline fungal infection. Duration of fever, hospital stay, and overall survival (OS) were studied. A total of 153 patients were randomized to receive micafungin or itraconazole. The overall success rate was 7.1 % point higher in the micafungin group (64.4 vs. 57.3 %, p = 0.404), satisfying the statistical criteria for the non-inferiority of micafungin. The duration of fever and hospital stay were significantly shorter in the micafungin group (6 vs. 7 days, p = 0.014; 22 vs. 27 days, p = 0.033, respectively). Grade 3 adverse events including hyperbilirubinemia (2 vs. 7), elevation of transaminase levels (2 vs. 4), electrolyte imbalance (1 vs. 2), atrial fibrillation (1 vs. 0), and anaphylaxis (1 vs. 0) occurred in 7 and 13 patients in the micafungin (10.4 %) and itraconazole (18.8 %) groups, respectively. Micafungin, when compared with itraconazole, had favorably comparable success rate and toxicity profiles on febrile neutropenia in patients with hematological malignancies. In addition, it showed superior effect on shortening the hospital stay.

show abstract

Micafungin activity against Candida albicans with diverse azole resistance phenotypes

Cited by 20 publications

References 37 publications

Activity Profile In Vitro of Micafungin against Spanish Clinical Isolates of Common and Emerging Species of Yeasts and Molds

Activity Profile In Vitro of Micafungin against Spanish Clinical Isolates of Common and Emerging Species of Yeasts and Molds

Inhibitors of the Candida albicans Major Facilitator Superfamily Transporter Mdr1p Responsible for Fluconazole Resistance

Efficacy and safety of micafungin versus intravenous itraconazole as empirical antifungal therapy for febrile neutropenic patients with hematological malignancies: a randomized, controlled, prospective, multicenter study

Contact Info

Product

Resources

About