Micafungin (
FK463) is an
echinocandin that demonstrates potent in vitro antifungal activities against Candida and Aspergillus species. However, little is known about its comparative antifungal activities in persistently neutropenic hosts. We therefore investigated the plasma
micafungin pharmacokinetics and antifungal activities of
micafungin against experimental disseminated
candidiasis and
invasive pulmonary aspergillosis in persistently neutropenic rabbits. The groups with disseminated
candidiasis studied consisted of untreated controls (UCs); rabbits treated with desoxycholate
amphotericin B (DAMB) at 1 mg/kg of
body weight/day; or rabbits treated with
micafungin at 0.25, 0.5, 1, and 2 mg/kg/day intravenously. Compared with the UCs, rabbits treated with
micafungin or DAMB showed significant dosage-dependent clearance of Candida albicans from the liver, spleen, kidney, brain, eye, lung, and vena cava. These in vivo findings correlated with the results of in vitro time-kill assays that demonstrated that
micafungin has concentration-dependent fungicidal activity. The groups with
invasive pulmonary aspergillosis studied consisted of UCs; rabbits treated with DAMB; rabbits treated with
liposomal amphotericin B (LAMB) at 5 mg/kg/day; and rabbits treated with
micafungin at 0.5, 1, and 2 mg/kg/day. In comparison to the significant
micafungin dosage-dependent reduction of the residual burden (in log CFU per gram) of C. albicans in tissue,
micafungin-treated rabbits with
invasive pulmonary aspergillosis had no reduction in the concentration of Aspergillus fumigatus in tissue. DAMB and LAMB significantly reduced the burdens of C. albicans and A. fumigatus in tissues (P < 0.01). Persistent
galactomannan antigenemia in
micafungin-treated rabbits correlated with the presence of an elevated burden of A. fumigatus in pulmonary tissue. By comparison, DAMB- and LAMB-treated animals had significantly reduced circulating
galactomannan antigen levels. Despite a lack of clearance of A. fumigatus from the lungs, there was a significant improvement in the rate of survival (P < 0.001) and a reduction in the level of
pulmonary infarction (P < 0.05) in
micafungin-treated rabbits. In summary,
micafungin demonstrated concentration-dependent and dosage-dependent clearance of C. albicans from persistently neutropenic rabbits with disseminated
candidiasis but not of A. fumigatus from persistently neutropenic rabbits with
invasive pulmonary aspergillosis.