title: Time-Kill Kinetics and In Vitro Antifungal Susceptibility of Non-fumigatus Aspergillus Species Isolated from Patients with Ocular Mycoses.
abstract: Aspergillus species can cause ocular morbidity and blindness, and thus, appropriate antifungal therapy is needed. We investigated the in vitro activity of itraconazole, voriconazole, posaconazole, caspofungin, anidulafungin, and amphotericin B against 14 Aspergillus isolates obtained from patients with ocular mycoses, using the CLSI reference broth microdilution methodology. In addition, time-kill assays were performed, exposing each isolate separately to 1-, 4-, and 16-fold concentrations above the minimum inhibitory concentration (MIC) of each antifungal agent. A sigmoid maximum-effect (E max) model was used to fit the time-kill curve data. The drug effect was further evaluated by measuring an increase/decrease in the killing rate of the tested isolates. The MICs of amphotericin B, itraconazole, voriconazole, and posaconazole were 0.5-1.0, 1.0, 0.5-1.0, and 0.25 µg/ml for A. brasiliensis, A. niger, and A. tubingensis isolates, respectively, and 2.0-4.0, 0.5, 1.0 for A. flavus, and 0.12-0.25 µg/ml for A. nomius isolates, respectively. A. calidoustus had the highest MIC range for the azoles (4.0-16.0 µg/ml) among all isolates tested. The minimum effective concentrations of caspofungin and anidulafungin were ≤0.03-0.5 µg/ml and ≤0.03 µg/ml for all isolates, respectively. Posaconazole demonstrated maximal killing rates (E(max) = 0.63 h(-1), r(2) = 0.71) against 14 ocular Aspergillus isolates, followed by amphotericin B (E(max) = 0.39 h(-1), r(2) = 0.87), voriconazole (E(max) = 0.35 h(-1), r(2) = 0.098), and itraconazole (E(max) = 0.01 h(-1), r(2) = 0.98). Overall, the antifungal susceptibility of the non-fumigatus Aspergillus isolates tested was species and antifungal agent dependent. Analysis of the kinetic growth assays, along with consideration of the killing rates, revealed that posaconazole was the most effective antifungal against all of the isolates.
authors.affiliation: Division of Mycology, Department of Microbiology, Faculty of Medicine, University of Eskisehir Osmangazi, Eskisehir, Turkey.
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Öz
authors.affiliation: Division of Ophthalmology, Medicosocial Health Center, University of Çukurova, Adana, Turkey.
authors.forename: Havva Gül
authors.initials: HG
authors.lastname: Özdemir
authors.affiliation: Department of Microbiology, Faculty of Medicine, University of Eskisehir Osmangazi, Eskisehir, Turkey.
authors.forename: Egemen
authors.initials: E
authors.lastname: Gökbolat
authors.affiliation: Division of Mycology, Department of Microbiology, Cerrahpasa Faculty of Medicine, University of Istanbul, Istanbul, Turkey.
authors.forename: Nuri
authors.initials: N
authors.lastname: Kiraz
authors.affiliation: Division of Mycology, Department of Microbiology, Faculty of Medicine, University of Çukurova, Adana, Turkey.
authors.forename: Macit
authors.initials: M
authors.lastname: Ilkit
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, ErasmusMC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands. S.Seyedmousavi@gmail.com.|Department of Medical Microbiology, Radboud UMC, Nijmegen, The Netherlands. S.Seyedmousavi@gmail.com.|Invasive Fungi Research Center, Mazandaran University of Medical Sciences, Sari, Iran. S.Seyedmousavi@gmail.com.
authors.forename: Seyedmojtaba
authors.initials: S
authors.lastname: Seyedmousavi
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D000077612:Anidulafungin; D000935:Antifungal Agents / Q000494:pharmacology*; D001228:Aspergillosis / Q000188:drug therapy* / Q000382:microbiology; D001230:Aspergillus / Q000187:drug effects* / Q000302:isolation & purification; D000077336:Caspofungin; D054714:Echinocandins / Q000494:pharmacology; D005123:Eye / Q000382:microbiology / Q000473:pathology; D015821:Eye Infections, Fungal / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology; D055666:Lipopeptides / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D014230:Triazoles / Q000494:pharmacology; D065819:Voriconazole / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D014230:Triazoles; D017964:Itraconazole; C101425:posaconazole; D000666:Amphotericin B; D000077612:Anidulafungin; D000077336:Caspofungin; D065819:Voriconazole
keywords: Antifungal susceptibility testing; Non-fumigatus Aspergillus spp.; Ophthalmic mycoses; Time-kill assay