Reports from the end of the 2000s forced the medical community to take azole resistance in Aspergillus fumigatus into account. Not only patients with chronic aspergillus disease, who develop resistance during long-term azole treatment, but also azole-naive patients are at risk, owing to the presence of resistant strains in the environment. The purpose of this review is to overview the latest findings concerning the origin, evolution, and implications of azole resistance in A. fumigatus.
TR34/L98H is the predominant resistance mechanism of environmental origin in A. fumigatus. Recent epidemiological data show that this mechanism is an expanding problem, with reports from China, Iran, and India. However, the TR34/L98H strains from the Middle East are genotypically different from the European isolates; their emergence is, therefore, not due to simple geographical spread of the ‘European’ isolates. A new environmental resistance mechanism, TR46/Y121F/T289A, was detected in the Netherlands, conferring voriconazole resistance. In patients chronically treated with triazoles, the spectrum of resistance has become more diverse, with the emergence of non-CYP51A-mediated mechanisms. Central registration of treatment and outcome data of patients with resistant aspergillus disease are needed.
Azole resistance in A. fumigatus is evolving to a global health problem.
aDepartment of Microbiology and Immunology, Catholic University of Leuven
bDepartment of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium
cDepartment of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
Correspondence to Paul E. Verweij, MD, PhD, UMC St Radboud Medical Microbiology, PO Box 9101, 6500 HB Nijmegen, the Netherlands. Tel: +31 24 361 43 56; fax: +31 24 354 02 16; e-mail: P.Verweij@mmb.umcn.nl