The Current Status of Drug-resistant Aspergillus.

Aspergillus spp. are important fungi because of the high mortality associated with aspergillosis. However, we have only three classes of anti-aspergillus drugs available; and only two drugs, itraconazole (ITCZ) and voriconazole (VRCZ), are available as oral agents in Japan. If azole-resistant Aspergillus causes chronic aspergillosis, we cannot treat such patients with oral azoles on an outpatient basis. As is the case with foreign countries, we found the existence of azole-resistant Aspergillus fumigatus in clinical settings in Japan. Resistance was attributed to mutations of the target protein (CYP51A). Additionally, we also found that long-term itraconazole treatment induced G54 substitution in CYP51A, causing itraconazole-resistance. Although there are few resistant Aspergillus strains existing in Japan now, we have to continue to find such resistant isolates, which are spreading worldwide.