Azole resistance in Aspergillus fumigatus

Invasive aspergillosis remains an important complication of immunosuppressive treatment regimens in humans. Triazoles are increasingly used in the prevention and management of invasive aspergillosis. Voriconazole is first choice for the primary therapy of invasive aspergillosis, and posaconazole was shown to be highly effective in preventing invasive aspergillus disease when given to high-risk groups prophylactically. Resistance in moulds is uncommon in clinical medicine, but might occur in specific patient groups. It appears that azole resistance might evolve in patients that harbor a high number of reproducing Aspergillus and are treated with azoles for long period of time. These conditions are present in patients with aspergilloma or other cavitary lung diseases caused by Aspergillus species. Azole resistance has been described to emerge in this patient group. Recently azole resistance was also reported in patients with acute invasive aspergillosis, where the conditions for resistance development appear to be less that optimal: fungal proliferation through hyphal elongation and relative short treatment episodes. This might suggest that azole resistance is caused by exposure outside the patient, for instance in the environment. Molecular studies have shown that triazole resistance in A. fumigatus is associated with amino acid substitutions in the cyp51A protein. Alterations might result in different patterns of azole resistance, primarily of itraconazole, with varying reduced activity of other triazoles such as voriconazole and posaconazole. Azole resistance in A. fumigatus has been associated with treatment failure. At present clinical microbiology laboratories do not routinely perform in vitro susceptibility testing, but it appears to be appropriate to test A. fumigatus isolates at least in those isolates recovered from patients that fail to azole therapy