title: In vitro and in vivo activities of posaconazole and amphotericin B in a murine invasive infection by Mucor circinelloides: poor efficacy of posaconazole.
abstract: The in vitro susceptibility of 17 strains of Mucor circinelloides to amphotericin B and posaconazole was ascertained by using broth microdilution and disk diffusion methods and by determining the minimal fungicidal concentration (MFC). We evaluated the efficacy of posaconazole at 40 mg/kg of body weight/day and amphotericin B at 0.8 mg/kg/day in a neutropenic murine model of disseminated infection by M. circinelloides by using 6 different strains tested previously in vitro. In general, most of the posaconazole MICs were within the range of susceptibility or intermediate susceptibility, while the small inhibition zone diameters (IZDs) were indicative of nonsusceptibility for all isolates tested. The MFCs were ≥ 3 dilutions higher than the corresponding MICs. In contrast, amphotericin B showed good activity against all of the strains tested regardless of the method used. The in vivo studies demonstrated that amphotericin B was effective in prolonging survival and reducing the fungal load. Posaconazole showed poor in vivo efficacy with no correlation with the MIC values. The results suggested that posaconazole should be used with caution in the treatment of infections caused by Mucor circinelloides or by strains of Mucor not identified to the species level.
authors.affiliation: Unitat de Microbiologia, Facultat de Medicina i Ciències de la Salut, IISPV, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Valentina
authors.initials: V
authors.lastname: Salas
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Pastor
authors.forename: Enrique
authors.initials: E
authors.lastname: Calvo
authors.forename: Eduardo
authors.initials: E
authors.lastname: Alvarez
authors.forename: Deanna A
authors.initials: DA
authors.lastname: Sutton
authors.forename: Emilio
authors.initials: E
authors.lastname: Mayayo
authors.forename: Anette W
authors.initials: AW
authors.lastname: Fothergill
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rinaldi
authors.forename: Josep
authors.initials: J
authors.lastname: Guarro
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000382:microbiology; D004195:Disease Models, Animal; D025141:Drug Resistance, Fungal; D007668:Kidney / Q000187:drug effects / Q000382:microbiology; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D009089:Mucor / Q000187:drug effects* / Q000502:physiology; D009091:Mucormycosis / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D009503:Neutropenia / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D013045:Species Specificity; D015996:Survival Rate; D017211:Treatment Failure; D014230:Triazoles / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole; D000666:Amphotericin B