Correlation of in vitro activity, serum levels, and in vivo efficacy of posaconazole against Rhizopus microsporus in a murine disseminated infection.
A broth microdilution method was used to evaluate the in vitro activities of seven antifungal agents against 15 clinical strains of Rhizopus microsporus. Amphotericin B (AMB) and posaconazole (POS) were the most active drugs. In a model of disseminated R. microsporus infection in immunosuppressed mice, we studied the efficacy of POS administered once or twice daily against four of the strains previously tested in vitro and compared it with that of liposomal AMB (LAMB). LAMB was the most effective treatment for the two strains with intermediate susceptibility to POS. For the two POS-susceptible strains, LAMB and POS at 20 mg/kg of body weight twice a day orally showed similar efficacies. The in vivo efficacy of POS administered twice a day orally correlated with the in vitro susceptibility data and the serum drug concentrations.
Unitat de Microbiologia, Facultat de Medicina i Ciències de la Salut, IISPV, Universitat Rovira i Virgili, Reus, Spain.
M Mar
MM
Rodríguez
F Javier
FJ
Pastor
Enrique
E
Calvo
Valentina
V
Salas
Deanna A
DA
Sutton
Josep
J
Guarro
D000666:Amphotericin B / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D000935:Antifungal Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000382:microbiology; D007668:Kidney / Q000187:drug effects / Q000382:microbiology; D008297:Male; D051379:Mice; D009091:Mucormycosis / Q000188:drug therapy* / Q000635:transmission; D012233:Rhizopus / Q000187:drug effects*; D014230:Triazoles / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
D000935:Antifungal Agents; D014230:Triazoles; C068538:liposomal amphotericin B; C101425:posaconazole; D000666:Amphotericin B