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The efficacy of liposomal amphotericin B and voriconazole was evaluated against the systemic infection by Fusarium oxysporum species complex or Fusarium keratoplasticum. Although MIC values were within the epidemiological cutoff values (ECVs) recently stablished for Fusarium spp., no efficacy was obtained, indicating that ECVs for Fusarium are not relevant for in vivo efficacy.

Rhodotorula infections have emerged in recent years causing mainly fungemia associated to high mortality. We have evaluated the in vitro activity of nine antifungal drugs against four clinical strains of Rhodotorula mucilaginosa, being amphotericin B, voriconazole and posaconazole the most active compounds. The experimental virulence of this fungus and the efficacy of the three mentioned drugs were evaluated in disseminated infections in neutropenic mice. Infection resulted in a high fungal load in all the organs studied without evident particular tropism. All treated animals showed reduced burden respect to the control in a strain dependent manner being voriconazole slightly superior to posaconazole and amphotericin B.

We have evaluated the in vitro activity of caspofungin against 36 wild-type strains of Candida parapsilosis sensu stricto using 3 techniques: broth microdilution, disk diffusion, and the determination of minimal fungicidal concentration (MFC). The first 2 methods showed a good in vitro activity of caspofungin, but the MFCs were ≥2 dilutions above their corresponding MICs. In a murine model of disseminated infection, we evaluated the efficacy of caspofungin at 5 mg/kg against 8 strains of C. parapsilosis representing different degrees of in vitro susceptibility (0.12–1 μg/mL). All the isolates responded to treatment and (1→3)-β-D-glucan levels were reduced in all the cases; however, the study revealed differences among isolates, since caspofungin reduced the tissue burden of mice infected with isolates with MICs ≤0.5 μg/mL but was less effective against those with MICs of 1 μg/mL.

Echinocandins are recommended as a first-line therapy for invasive candidiasis. Candida rugosa was recently transferred to the new genus Diutina. We have determined the in vitro killing kinetics of two echinocandins, anidulafungin, and caspofungin and their in vivo efficacy, administering doses of 5 or 10 mg/kg, and 1 or 5 mg/kg, respectively against 2 clinical strains of D. rugosa. Both drugs showed a fungicidal concentration-dependent activity and, in a neutropenic murine model of disseminated infection, were able to reduce tissue burden and to prolong survival of mice. These results suggest that both echinocandins could be useful to treat infections by this fungus when isolates show minimal inhibitory concentrations within the range of susceptibility for both drugs.

Because human infections by Scedosporium prolificans are difficult to treat and show a very poor outcome, new therapeutic strategies are needed. Liposomal amphotericin B (LAMB) (40 mg/kg/day) increased significantly the mean survival time in immunosuppressed mice compared with a control group (22.6 vs. 8.8 days). Amphotericin B deoxycholate (1.5 mg/kg/day) and granulocyte colony-stimulating factor (G-CSF) (300 microg/kg/day) were ineffective. The combination of LAMB (40 mg/kg/day) and G-CSF (150 or 300 microg/kg/day) did not improve the results obtained with LAMB alone.

We have studied the in vitro interactions of amphotericin B (AMB) with terbinafine (TBF), itraconazole, voriconazole (VCZ), albaconazole, and ravuconazole (RVZ), as well as TBF combined with the same azoles, against 11 isolates of Fusarium spp. using the fractional inhibitory concentration index. The highest percentage of synergistic interactions was observed for the combinations AMB-RVZ, TBF-VCZ, and TBF-RCZ.