Antifungal susceptibility of Aspergillus fumigatus clinical isolates collected from various areas in Japan.

Azole resistance among clinical isolates of Aspergillus fumigatus is becoming a serious problem in Europe, but the status in Japan is not yet known in detail. The aim of this study was to determine the present status of azole resistance in A. fumigatus in Japan. We employed 171 clinical isolates of A. fumigatus sensu stricto collected from 1987 to 2008 at the Medical Mycology Research Center, Chiba University, Japan for azole resistance determination. Identification of all isolates were re-examined both from the aspect of morphology and molecular phylogeny. The antifungal susceptibility of these isolates was tested based on the CLSI M38-A2 broth microdilution method. In our collection, only 1 (0.6%) and 2 isolates (1.2%) showed elevated MIC to voriconazole and itraconazole, respectively. Our study disclosed that the frequency of azole resistance in A. fumigatus still remains low in this collection.

[Fungicidal activity of liranaftate against dermatophytes].

The fungicidal activities of the thiocarbamate antifungal agent liranaftate were compared to those of luliconazole, amorolfine hydrochloride and ketoconazole against twelve stock strains of three species of dermatophytes. The MICs of 0.001-0.009 microg/ml of luliconazole against Trichophyton rubrum (n=6)were the lowest among the agents tested, but its MCCs were considerably higher. Consequently, the antifungal potency of luliconazole was considered fungistatic. In contrast to this, the MCCs of 0.009-0.039 microg/ml of liranaftate against T. rubrum were the lowest and similar to its MICs. These results showed that liranaftate was fungicidal. All antifungals except ketoconazole tended to be fungicidal against both T. mentagrophytes (n=3)and Microsporum gypseum (n=3). In time-kill studies, liranaftate showed the greatest decrease to a below detection limit in viable counts of T. rubrum. The degree of killing of the strain by amorolfine was not greater than that seen by liranaftate, and little reduction of the viable counts by luliconazole and ketoconazole was observed irrespective of concentrations of the agents. Conversely, there were no differences among four agents in fungicidal activities against T.mentagrophytes. The killing activities of liranaftate against M. gypseum were also higher than those of comparable agents, as true of T. rubrum described above. In this study we found that it was harder to kill T. rubrum than other dermatophytes. Therefore, liranaftate with its potent fungicidal activities was suggested an efficacious agent for the treatment of dermatophytes.

Antimicrobial activities of hydrophobic 2-arylbenzofurans and an isoflavone against vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus.

Eight 2-arylbenzofurans and an isoflavone isolated from medicinal plants were tested for their antimicrobial activities against vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA). Among these compounds, six hydrophobic 2-arylbenzofurans (log P = 4.4-8.7) exhibited considerable antibacterial activity against five VRE strains(VanA-, VanB-, and VanC-phenotypes) (MICs = 3.13-6.25 microg/mL). Five compounds also showed antibacterial activity against ten MRSA strains (MIC80 = 3.13 microg/mL).

Antimicrobial activity of hydrophobic xanthones from Cudrania cochinchinensis against Bacillus subtilis and methicillin-resistant Staphylococcus aureus.

Ten xanthones with one or two isoprenoid groups and a prenylated benzophenone isolated from roots of Cudrania cochinchinensis (Moraceae) were tested for their antimicrobial activities against Bacillus subtilis and methicillin-resistant Staphylococcus aureus (MRSA). Among these compounds, gerontoxanthone H exhibited considerable antibacterial activity against B. subtilis (MIC = 1.56 microg/ml). Four xanthones, gerontoxanthone I, toxyloxanthone C, cudraxanthone S, and 1,3,7-trihydroxy-2-prenylxanthone, showed weak antibacterial activity against the bacterium (MICs = 3.13-6.25 microg/ml). These compounds also exhibited similar MIC values against methicillin-sensitive S. aureus, MRSAs, and Micrococcus luteus.

[Fungicidal activity of liranaftate against Trichophyton rubrum].

The fungicidal activities of thiocarbamate antifungal agent liranaftate were studied by determining the MIC and the MCC against Trichophyton rubrum with the Milliflex -100 Test System and by determining the time-kill curve in comparison to that of six reference agents. Liranaftate and lanoconazole both showed excellent fungistatic activity against the conidia of T. rubrum. For each of these agents, the MIC after 14 days of contact was 0.009 g/ml. The liranaftate-induced decrease in the MCC occurred from 9 days onwards; MCC at 14 days was 0.039 g/ml. The MCC for tolciclate was also reduced from 9 days onwards, but that of amorolfine, lanoconazole, neticonazole, clotrimazole and bifonazole was not lowered up to 14 days. Similar results were obtained when the studies were performed with germinated conidia. The time-kill curves showed that both liranaftate and tolciclate, at concentrations ranging from 2 to 32 times the MICs, achieved a decrease in viable counts to below the detection limit within 7 to 9 days. In experiments with low levels of inoculum, only amorolfine produced a decrease to below the detection level, and that occurred at 14 days; no reduction in viable counts was observed up to 14 days with the four azole agents. Our data suggest that antifungal agents of the thiocarbamate class possess the most potent fungicidal activity against dermatophytes; these are followed in order by morpholine and azole antifungals.