title: In vitro activity of anidulafungin in combination with amphotericin B or voriconazole against biofilms of five Candida species.
abstract: To evaluate the in vitro activity of anidulafungin combined with amphotericin B or voriconazole against Candida spp. biofilms.
  
  
  
  Four Candida albicans, four Candida tropicalis, four Candida glabrata, two Candida parapsilosis and two Candida orthopsilosis blood isolates were tested by the microdilution chequerboard method combined with the XTT metabolic assay. Biofilm MIC was defined as the lowest concentration producing 50% metabolic inhibition with respect to control (BMIC50). Concentrations in the combinations ranged from 1/8 × BMIC50to 4 × BMIC50found for each antifungal tested alone.
  
  
  
  Anidulafungin plus amphotericin B acted synergistically against C. albicans and C. glabrata biofilms [fractional inhibitory concentration index (FICI): 0.082-0.387], but showed no interaction against C. tropicalis, C. parapsilosis and C. orthopsilosis (FICI: 0.516-2.099). The combination of these antifungals failed to completely remove biofilms of C. albicans and C. glabrata, decreasing the metabolic activity of the biofilms up to 80% and 95%, respectively, which did not occur when each antifungal was used alone. Anidulafungin plus voriconazole showed no interaction against all isolates. Using a less stringent criterion previously proposed to define synergism (FICI < 1) and antagonism (FICI > 1.25), antagonistic interactions were found against some isolates.
  
  
  
  Anidulafungin with amphotericin B results in a synergistic effect against C. albicans and C. glabrata biofilms at serum concentrations of the drugs, but showed no interaction against C. tropicalis and C. parapsilosis complex. Anidulafungin plus voriconazole showed no interaction against the five Candida species assayed. Biofilms of C. tropicalis were found to be the most resistant towards the combinations assayed. The results presented may be of potential interest in the clinical setting.
authors.affiliation: Servicio de Microbiología, Hospital Universitario y Politécnico La Fe, Valencia, Spain.|Grupo Infección Grave, Instituto Investigación Sanitaria La Fe, Valencia, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Valentín
authors.affiliation: Grupo Infección Grave, Instituto Investigación Sanitaria La Fe, Valencia, Spain canton_emi@gva.es.
authors.forename: E
authors.initials: E
authors.lastname: Cantón
authors.affiliation: Servicio de Microbiología, Hospital Universitario y Politécnico La Fe, Valencia, Spain.|Grupo Infección Grave, Instituto Investigación Sanitaria La Fe, Valencia, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Pemán
authors.affiliation: Grupo Infección Grave, Instituto Investigación Sanitaria La Fe, Valencia, Spain.
authors.forename: M E
authors.initials: ME
authors.lastname: Fernandez-Rivero
authors.affiliation: Grupo Infección Grave, Instituto Investigación Sanitaria La Fe, Valencia, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Tormo-Mas
authors.affiliation: Departamento de Microbiología y Ecología, Facultad de Farmacia, Universitat de València, Valencia, Spain.
authors.forename: J P
authors.initials: JP
authors.lastname: Martínez
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology*; D000077612:Anidulafungin; D000935:Antifungal Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D002175:Candida / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology; D058387:Candidemia / Q000382:microbiology; D004357:Drug Synergism; D054714:Echinocandins / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D065819:Voriconazole / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D000666:Amphotericin B; D000077612:Anidulafungin; D065819:Voriconazole