Antifungal activity of miltefosine against both azole-susceptible and -resistant Aspergillus strains |
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| Institution: | 1. Invasive Fungi Research Centre, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran;2. Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Mazandaran Province, Iran;3. Department of Molecular Microbiology & Immunology, South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, Texas, USA;4. Department of Nano-biomedicine, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran;5. Natural and Medical Sciences Research Centre, University of Nizwa, Nizwa, Oman;6. Department of Dermatology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran;7. Centre of Expertise in Mycology, Radboud University Medical Centre/Canisius Wilhelmina Hospital, Nijmegen, The Netherlands;1. Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy;2. Clinical Pharmacology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy;3. Infectious Diseases Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy;4. Division of Microbiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy;1. UMR 1173, Versailles Saint-Quentin University, Versailles, France;2. Raymond Poincaré Paris Saclay University Hospital, Garches, France;3. FHU PROTHEE, St Louis Hospital, Paris-Cité University, Paris, France;4. CIC, Raymond Poincaré Paris Saclay University Hospital, Garches, France;5. Microbiology Unit, Raymond Poincaré Paris Saclay University Hospital, Garches, France;6. Toxicology Unit, Bichat Paris Nord University Hospital, Paris, France;7. Institut for Infectious Agents, Department of Bacteriology - CNR des staphylocoques, Croix-Rousse Hospital, North Biology Centre, Hospices Civils de Lyon, Lyon, France;8. Team “Staphylococcal pathogenesis”, International Centre for Infectiology Research, INSERM U1111 - CNRS UMR5308 - ENS Lyon - Lyon 1 University, Lyon, France;1. Department of Pathology and Microbiology, Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, Quebec, Canada;2. Groupe de Recherche et d''Enseignement en Salubrité Alimentaire, Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, Quebec, Canada;3. Swine and Poultry Infectious Diseases Research Center, Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, Quebec, Canada;4. Unité Antibiorésistance et Virulence Bactériennes – Agence Nationale de Sécurité Sanitaire, Université de Lyon, Lyon, France;5. One Health Trust, Washington, DC 20005, Princeton University, Princeton NJ 08544, USA;1. Paediatric Intensive Care, Department of Heart and Lung, Great Ormond Street Hospital for Children, London WC1N 3JH, UK;2. Paediatric Infectious Diseases, University of Oxford, Oxford OX1 4BH, UK;3. Project DRIVE Data Science, Great Ormond Street Hospital for Children, London WC1N 3JH, UK;4. Department of Pharmacy, Great Ormond Street Hospital for Children, London WC1N 3JH, UK;5. Department of Microbiology, Great Ormond Street Hospital for Children, London WC1N 3JH, UK;1. Infectious Disease Pharmacokinetics Lab, Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA;2. Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA;3. Department of Pharmacy, UF Health Shands Hospital, Gainesville, FL, USA;4. North West Ventilation Unit, Manchester University NHS Foundation Trust, Manchester, UK;5. Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK;6. Department of Pharmacology and Clinical Pharmacology, Christian Medical College, Vellore, India. |
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| Abstract: | Miltefosine, an alkylphosphocholine, has been approved recently for the treatment of visceral leishmaniasis. Miltefosine has shown promise as a treatment for paracoccidioidomycosis, and has mixed activity against other fungi and yeast. There are limited data on the in-vitro activity of miltefosine against azole-resistant and -susceptible Aspergillus spp. As such, the aim of this study was to determine the in-vitro activity of miltefosine against Aspergillus strains. Miltefosine was tested against 108 azole-susceptible and -resistant Aspergillus strains isolated from Iran and other countries using the broth microdilution method. Miltefosine was found to be effective against azole-resistant Aspergillus isolates, with minimum inhibitory concentrations (MICs) ranging from 1.562 to 6.25 µg/mL. MIC50 and MIC90 were 1.562 and 3.125 µg/mL, respectively. Miltefosine had a higher geometric mean MIC (2.459 µg/mL) for wild-type Aspergillus isolates than itraconazole (0.220 µg/mL) and voriconazole (0.298 µg/mL). No significant difference was found between miltefosine MICs for azole-resistant Aspergillus isolates and azole-susceptible Aspergillus isolates (P>0.05). Miltefosine appears to have good in-vitro activity against azole-resistant Aspergillus strains, according to these findings. Furthermore, the findings suggest that miltefosine could be used to treat infections caused by azole-resistant Aspergillus spp. |
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