title: Decreased Killing Activity of Micafungin Against Candida guilliermondii, Candida lusitaniae, and Candida kefyr in the Presence of Human Serum.
abstract: Currently, echinocandins are first-line drugs for treatment of invasive candidiasis. However, data on how serum influences killing activity of echinocandins against uncommon Candida species are limited. Therefore, the killing activity of micafungin in RPMI-1640 and in 50% serum was compared against Candida guilliermondii, Candida lusitaniae, and Candida kefyr. Minimum inhibitory concentration (MIC) ranges in RPMI-1640 were 0.5-1, 0.12-0.25, and 0.06-0.12 mg/L, respectively. In 50% serum, MICs increased 32- to 256-fold. In RPMI-1640 ≥ 0.25, ≥4, and 32 mg/L micafungin was fungicidal against all four C. kefyr (≤4.04 hours), two of three C. lusitaniae (≤16.10 hours), and two of three C. guilliermondii (≤12.30 hours), respectively. In 50% serum, all three species grew at ≤4 mg/L. Micafungin at 16-32 mg/L was fungicidal against all C. kefyr isolates (≤3.03 hours) and at 32 mg/L was fungistatic against one of three C. lusitaniae isolates. Two C. lusitaniae isolates and all three C. guilliermondii grew at all tested concentrations. Adding human serum to susceptibility test media drew attention to loss of fungicidal or fungistatic activity of micafungin in the presence of serum proteins, which is not predicted by MICs in case of C. kefyr and C. lusitaniae in RPMI-1640. Our results strongly suggest that micafungin and probably other echinocandins should be used with caution against rare Candida species.
authors.affiliation: 1 Department of Medical Microbiology, Faculty of Medicine, University of Debrecen , Debrecen, Hungary .
authors.forename: Qasem
authors.initials: Q
authors.lastname: Saleh
authors.affiliation: 1 Department of Medical Microbiology, Faculty of Medicine, University of Debrecen , Debrecen, Hungary .
authors.forename: Renátó
authors.initials: R
authors.lastname: Kovács
authors.affiliation: 1 Department of Medical Microbiology, Faculty of Medicine, University of Debrecen , Debrecen, Hungary .
authors.forename: Gábor
authors.initials: G
authors.lastname: Kardos
authors.affiliation: 2 Department of Pharmacology and Pharmacodynamics, University of Debrecen , Debrecen, Hungary .
authors.forename: Rudolf
authors.initials: R
authors.lastname: Gesztelyi
authors.affiliation: 1 Department of Medical Microbiology, Faculty of Medicine, University of Debrecen , Debrecen, Hungary .|3 Department of Pulmonology, Faculty of Medicine, University of Debrecen , Debrecen, Hungary .
authors.forename: Tamás
authors.initials: T
authors.lastname: Kardos
authors.affiliation: 1 Department of Medical Microbiology, Faculty of Medicine, University of Debrecen , Debrecen, Hungary .
authors.forename: Aliz
authors.initials: A
authors.lastname: Bozó
authors.affiliation: 1 Department of Medical Microbiology, Faculty of Medicine, University of Debrecen , Debrecen, Hungary .
authors.forename: László
authors.initials: L
authors.lastname: Majoros
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D001798:Blood Proteins / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D054714:Echinocandins / Q000494:pharmacology*; D006801:Humans; D055666:Lipopeptides / Q000494:pharmacology*; D000077551:Micafungin; D008826:Microbial Sensitivity Tests / Q000379:methods; D044967:Serum / Q000378:metabolism*
chemical_list: D000935:Antifungal Agents; D001798:Blood Proteins; D054714:Echinocandins; D055666:Lipopeptides; D000077551:Micafungin
keywords: 50% serum; echinocandins; killing rate; uncommon Candida species