Activity of posaconazole combined with amphotericin B against Aspergillus flavus infection in mice: comparative studies in two laboratories.
Posaconazole and/or amphotericin B was given to mice pretreated with a steroid and then infected by inhalation of Aspergillus flavus conidia. Two laboratories conducted studies using almost identical protocols to evaluate both survival and lung tissue burdens 8 days after infection. The results of the in vivo studies performed at both laboratories were consistent. We found that (i). up to 5 mg of amphotericin B per kg of body weight was poorly effective in treating invasive aspergillosis; (ii). posaconazole at 2 or 10 mg/kg/dose prolonged survival and reduced lung tissue CFU; and (iii). there was generally no antagonistic interaction of the drugs in combination, even when the experiments were designed to maximize the likelihood of antagonism. These studies do not confirm the antagonistic interaction of triazoles and polyenes reported by others.
Department of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900, USA. Najvar@uthscsa.edu
Laura K
LK
Najvar
Anthony
A
Cacciapuoti
Steve
S
Hernandez
Judith
J
Halpern
Rosie
R
Bocanegra
Maya
M
Gurnani
Frederick
F
Menzel
David
D
Loebenberg
John R
JR
Graybill
D000666:Amphotericin B / Q000627:therapeutic use*; D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy* / Q000382:microbiology*; D001231:Aspergillus flavus; D015169:Colony Count, Microbial; D008168:Lung / Q000382:microbiology; D051379:Mice; D016019:Survival Analysis; D014230:Triazoles / Q000627:therapeutic use*
D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole; D000666:Amphotericin B