Azole Antifungal Resistance Today: Focus on Aspergillus
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Oral triazole therapy is well established for the treatment of invasive aspergillosis (IPA), allergic aspergillosis (ABPA), and chronic pulmonary aspergillosis (CPA), and is often long-term. Resistance to triazole azole antifungal drugs in Aspergillus fumigatus is now a major clinical problem in a number of European locations, in China, Canada and the USA with particularly high frequencies from the north-west of the UK, and The Netherlands. A number of centers are reporting the continuing increasing frequency and evolution of resistance mechanisms in A. fumigatus, in both azole-naïve and patients treated with azoles. The increasing rate of resistance is of concern. A number of resistance mechanisms have been found. The biofilm modality of Aspergillus growth may have a number of therapeutic implications for aspergillosis, including antifungal resistance. Microbiological diagnosis of aspergillosis is limited by poor culture yield, leading to uncertainty about the frequency of triazole resistance. Direct resistance testing in culture-negative clinical samples may add additional insights into the prevalence of azole resistance in A. fumigatus.
KeywordsAspergillus fumigatus Azole antifungals Resistance
Paul Bowyer has received a grant from Astra Zeneca and stock options from Alergenetica SL; David W. Denning has served as a consultant for Lab21 Ltd and F2G Ltd, has been employed by The University of Manchester, and the National Institute of Allergy and Infectious Diseases, USA. He has also received grants and honoraria from Pfizer, Astellas, Myconostica, Merck, and Gilead, and patents from Myconostica; Malcolm D. Richardson has been a consultant and honoraria recipient for Gilead, Astellas, Pfizer, Cephalon, and Schering-Plough. He has also received payment for development of educational presentations from Gilead, Astellas, Pfizer, and Schering Plough, as well as travel and accommodation expense reimbursement from Gilead and Astellas. Riina Rautemaa and Caroline B. Moore reported no potential conflicts of interest relevant to this article.
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- 1.HPA Advisory Committee for Fungal Infection and Superficial Parasites. Fungal Diseases in the UK – 2006 http://www.hpa.org.uk/web/HPAwebFile/HPAweb_C/1196942156347
- 10.Richardson MD, Warnock DW: Fungal Infection: Diagnosis and Management, 4th Edition. Wiley-Blackwell, Chichester, 2012 (in press).Google Scholar
- 20.• Warris A, Weemaes CM, Verweij PE. Multidrug resistance in Aspergillus fumigatus. N Engl J Med. 2002;347:2173–4. The first report of the emergence of multidrug resistance against azole antifungals. An illustrative case report demonstrated that long-term prophylaxis with itraconazole resulted in infection with A. fumigatus strains that were resistant to azoles.PubMedCrossRefGoogle Scholar
- 25.•• Snelders E, Melchers WJ, Verweij PE. Azole resistance in Aspergillus fumigatus: a new challenge in the management of invasive aspergillosis? Future Microbiol. 2011;6:335–47. A timely, comprehensive review of azole resistance in Aspergillus fumigatus and the implications for treating patients with invasive aspergillosis.PubMedCrossRefGoogle Scholar
- 26.•• Bueid A, Howard SJ, Moore CB, et al. Azole antifungal resistance in Aspergillus fumigatus: 2008 and 2009. J Antimicrob Chemother. 2010;65:2116–8. This report updates the level of azole resistance in Aspergillus fumigatus seen in isolates from patients attending the National Aspergillosis Centre, UK.PubMedCrossRefGoogle Scholar
- 27.•• Denning DW, Park S, Lass-Florl C, et al. High-frequency triazole resistance found in nonculturable Aspergillus fumigatus from lungs of patients with chronic fungal disease. Clin Infect Dis. 2011;52:1123–9. This study describes the direct detection of resistance in culture-negative clinical samples using rapid molecular methods to detect resistance markers. Using this approach a high rate of azole resistance (55.1%).PubMedCrossRefGoogle Scholar
- 32.Howard SJ, Harrison E, Bowyer P, et al.: Cryptic species and azole resistance in the Aspergillus niger complex. Antimicrob Agents Chemother. 2011. [Epub ahead of print].Google Scholar