title: In vitro antifungal susceptibility of filamentous fungi causing rare infections: synergy testing of amphotericin B, posaconazole and anidulafungin in pairs.
abstract: OBJECTIVE
  Mucormycetes (formerly known as zygomycetes of the order Mucorales) and hyaline moulds such as those of the genus Fusarium or Paecilomyces are emerging as significant human pathogens. The aim of the study was to determine the in vitro antifungal susceptibility of these fungi to older and newer antifungals and to investigate the antifungal activity of amphotericin B, posaconazole and anidulafungin in dual combinations.
  
  
  METHODS
  Twenty-one clinical isolates of mucormycetes and 16 of rare hyaline moulds were tested. MICs were determined by EUCAST methodology for conidia-forming moulds and Etesting. For antifungal combinations a chequerboard method based on EUCAST methodology was used.
  
  
  RESULTS
  Against mucormycetes, amphotericin B exhibited the lowest MICs, followed by posaconazole. Ravuconazole was active against eight of the Rhizopus isolates (MIC 1 mg/L). Resistance to amphotericin B (MIC ≥ 2 mg/L) and posaconazole (MICs ≥ 4 mg/L) was observed in five and three Rhizopus isolates, respectively. Among Fusarium species variable susceptibility patterns were detected. Amphotericin B exhibited the lowest MICs, followed by voriconazole. Etesting for amphotericin B and posaconazole had excellent agreement with EUCAST methodology (78.6%-100%). Synergy between amphotericin B and anidulafungin was observed against two isolates (one Mucor circinelloides and one Fusarium proliferatum). Synergy or antagonism was not detected in any other combination.
  
  
  CONCLUSIONS
  The study showed that mucormycetes and other rare hyaline moulds exhibit variable susceptibilities to antifungals, and hence antifungal testing is valuable. The fact that the combination of amphotericin B with anidulafungin was found synergistic in some cases merits further investigation.
authors.affiliation: Infectious Diseases and Antimicrobial Chemotherapy Research Laboratory, 4th Department of Medicine, 'Attikon' Hospital, National and Kapodistrian University of Athens, Athens, Greece. mdrogari@hotmail.com
authors.forename: Maria
authors.initials: M
authors.lastname: Drogari-Apiranthitou
authors.forename: Foteini-Despina
authors.initials: FD
authors.lastname: Mantopoulou
authors.forename: Anna
authors.initials: A
authors.lastname: Skiada
authors.forename: Lambrini
authors.initials: L
authors.lastname: Kanioura
authors.forename: Maria
authors.initials: M
authors.lastname: Grammatikou
authors.forename: Georgia
authors.initials: G
authors.lastname: Vrioni
authors.forename: Aggeliki
authors.initials: A
authors.lastname: Mitroussia-Ziouva
authors.forename: Athanassios
authors.initials: A
authors.lastname: Tsakris
authors.forename: George
authors.initials: G
authors.lastname: Petrikkos
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology*; D000077612:Anidulafungin; D000935:Antifungal Agents / Q000494:pharmacology*; D004357:Drug Synergism; D054714:Echinocandins / Q000494:pharmacology*; D005658:Fungi / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008826:Microbial Sensitivity Tests; D009181:Mycoses / Q000382:microbiology; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D014230:Triazoles; C101425:posaconazole; D000666:Amphotericin B; D000077612:Anidulafungin