title: Combination of Amphotericin B and Flucytosine against Neurotropic Species of Melanized Fungi Causing Primary Cerebral Phaeohyphomycosis.
abstract: Primary central nervous system phaeohyphomycosis is a fatal fungal infection due mainly to the neurotropic melanized fungiCladophialophora bantiana,Rhinocladiella mackenziei, andExophiala dermatitidis.Despite the combination of surgery with antifungal treatment, the prognosis continues to be poor, with mortality rates ranging from 50 to 70%. Therefore, a search for a more-appropriate therapeutic approach is urgently needed. Ourin vitrostudies showed that with the combination of amphotericin B and flucytosine against these species, the median fractional inhibitory concentration (FIC) indices for strains ranged from 0.25 to 0.38, indicating synergy. By use of Bliss independence analysis, a significant degree of synergy was confirmed for all strains, with the sum ΔE ranging from 90.2 to 698.61%. No antagonism was observed. These results indicate that amphotericin B, in combination with flucytosine, may have a role in the treatment of primary cerebral infections caused by melanized fungi belonging to the orderChaetothyriales Furtherin vivostudies and clinical investigations to elucidate and confirm these observations are warranted.
authors.affiliation: Shanghai Institute of Medical Mycology, Changzheng Hospital, Second Military Medical University, Shanghai, China First Hospital of Xinjiang Medical University, Xinjiang, China.
authors.forename: S
authors.initials: S
authors.lastname: Deng
authors.affiliation: Shanghai Institute of Medical Mycology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: W
authors.initials: W
authors.lastname: Pan
authors.affiliation: Shanghai Institute of Medical Mycology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: W
authors.initials: W
authors.lastname: Liao
authors.affiliation: CBS-KNAW Fungal Biodiversity Centre, Utrecht, The Netherlands Institute for Biodiversity and Ecosystem Dynamics, University of Amsterdam, Amsterdam, The Netherlands King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: G S
authors.initials: GS
authors.lastname: de Hoog
authors.affiliation: CBS-KNAW Fungal Biodiversity Centre, Utrecht, The Netherlands Institute for Biodiversity and Ecosystem Dynamics, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: A H G
authors.initials: AH
authors.lastname: Gerrits van den Ende
authors.affiliation: CONICET, Buenos Aires, Argentina Ramos Mejia Hospital, Parasitology Unit, Mycology Section, Buenos Aires, Argentina.
authors.forename: R G
authors.initials: RG
authors.lastname: Vitale
authors.affiliation: Department of Biochemistry, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Rafati
authors.affiliation: Division of Mycology, Department of Microbiology, Faculty of Medicine, University of Çukurova, Adana, Turkey.
authors.forename: M
authors.initials: M
authors.lastname: Ilkit
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: A H
authors.initials: AH
authors.lastname: Van der Lee
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: A J M M
authors.initials: AJ
authors.lastname: Rijs
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: P E
authors.initials: PE
authors.lastname: Verweij
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands Invasive Fungi Research Center, Mazandaran University of Medical Sciences, Sari, Iran S.Seyedmousavi@gmail.com.
authors.forename: S
authors.identifier: http://orcid.org/0000-0002-6194-7447
authors.initials: S
authors.lastname: Seyedmousavi
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D060425:Cerebral Phaeohyphomycosis / Q000382:microbiology / Q000473:pathology; D003470:Culture Media / Q000737:chemistry; D004338:Drug Combinations; D004357:Drug Synergism; D005093:Exophiala / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification / Q000472:pathogenicity; D005163:Factor Analysis, Statistical; D005437:Flucytosine / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D004718:Saccharomycetales / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification / Q000472:pathogenicity
chemical_list: D000935:Antifungal Agents; D003470:Culture Media; D004338:Drug Combinations; D000666:Amphotericin B; D005437:Flucytosine
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