Isolate submission opportunity: Monitoring for Azole Resistance in Aspergillus fumigatus

The environmental mold Aspergillus fumigatus is the primary cause of invasive aspergillosis. In patients with high-risk conditions, including stem cell and organ transplant recipients, mortality exceeds 50%. Triazole antifungals have greatly improved survival;1 however, triazole-resistant A. fumigatus infections are increasingly reported worldwide and are associated with increased treatment failure and mortality.2

Of particular concern are resistant A. fumigatus isolates carrying either TR34/L98H or TR46/Y121F/T289A genetic resistance markers, which have been associated with environmental triazole fungicide use rather than previous patient exposure to antifungals.3,4 Reports of these triazole-resistant A. fumigatus strains have become common in Europe,2,3 but U.S. reports are limited.5,6 As most U.S. hospitals do not perform mold susceptibility testing, the extent of azole resistance in A. fumigatus in the U.S. is not known.  Understanding the prevalence of azole resistant patient isolates is important to guide clinical and public health decision-making.

The Centers for Disease Control and Prevention is requesting all A. fumigatus isolates from clinical laboratories regardless of whether or not they are a cause of infection. We will screen these isolates for resistance to the medical triazoles itraconazole and voriconazole, and will sequence resistant isolates for specific mutations linked with resistance.

To submit isolates, please email Sabrina Singleton for the Global File Accessioning Template (GFAT) as well as for instructions on using the GFAT, at aspergillus@cdc.gov.

References
  1. Patterson TF, Thompson GR, 3rd, Denning DW, Fishman JA, Hadley S, Herbrecht R, Kontoyiannis DP, Marr KA, Morrison VA, Nguyen MH, Segal BH, Steinbach WJ, Stevens DA, Walsh TJ, Wingard JR, Young JA, Bennett JE. 2016. Executive Summary: Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis 63:433-42.
  2. van der Linden JW, Arendrup MC, Warris A, Lagrou K, Pelloux H, Hauser PM, Chryssanthou E, Mellado E, Kidd SE, Tortorano AM, Dannaoui E, Gaustad P, Baddley JW, Uekotter A, Lass-Florl C, Klimko N, Moore CB, Denning DW, Pasqualotto AC, Kibbler C, Arikan-Akdagli S, Andes D, Meletiadis J, Naumiuk L, Nucci M, Melchers WJ, Verweij PE. 2015. Prospective multicenter international surveillance of azole resistance in Aspergillus fumigatus. Emerg Infect Dis 21:1041-4.
  3. Vermeulen E, Lagrou K, Verweij PE. 2013. Azole resistance in Aspergillus fumigatus: a growing public health concern. Curr Opin Infect Dis 26:493-500.
  4. Verweij PE, Chowdhary A, Melchers WJ, Meis JF. 2016. Azole Resistance in Aspergillus fumigatus: Can We Retain the Clinical Use of Mold-Active Antifungal Azoles? Clin Infect Dis 62:362-8.
  5. Beer KD, Farnon EC, Jain S, Jamerson C, Lineberger S, Miller J, Berkow EL, Lockhart SR, Chiller T, Jackson BR. 2018. Multidrug-Resistant Aspergillus fumigatus Carrying Mutations Linked to Environmental Fungicide Exposure – Three States, 2010-2017. MMWR Morb Mortal Wkly Rep 67:1064-1067.
  6. Wiederhold NP, Gil VG, Gutierrez F, Lindner JR, Albataineh MT, McCarthy DI, Sanders C, Fan H, Fothergill AW, Sutton DA. 2016. First Detection of TR34 L98H and TR46 Y121F T289A Cyp51 Mutations in Aspergillus fumigatus Isolates in the United States. J Clin Microbiol 54:168-71.