Antifungal Resistance in Aspergillus

Illustration of the Aspergillus pathogen

Medical illustration of azole-resistant Aspergillus fumigatus, presented in CDC’s Antibiotic Resistance Threats in the United States, 2019.

How Aspergillus develops antifungal resistance and causes illness

Antifungal resistance is an increasing problem with the fungus Aspergillus, a mold that can cause the infection aspergillosis. Infections that are resistant to antifungal drugs are difficult to treat. The resistance can occur in the environment and in patients who are sick with an Aspergillus infection and have been taking antifungal drugs for a long time.

Aspergillus infections can cause life-threatening illness in people who have weakened immune systems, have underlying diseases, or have had transplants. An estimated 200,000 cases of these infections occur worldwide every year.1

The preferred treatments for Aspergillus infections are the drug voriconazole and certain other azole drugs. However, resistance to certain antifungal drugs can develop in people who have taken them. Some people are more at risk for antifungal resistant infections — in some areas, 19% of Aspergillus infections are estimated to be resistant to azole medications.2 In a large U.S. study, antifungal resistance was identified in up to 7% of Aspergillus specimens from patients with stem cell and organ transplants.3-5

Resistant Aspergillus infections are also found in people who have not taken antifungal drugs, suggesting that the resistance is partially driven by environmental sources.6 For example, research shows that treating crop diseases with azole fungicides, which are similar to azole drugs like voriconazole, can lead to the growth of resistant strains of Aspergillus in soil and other places in the environment.7-10 If people with weakened immune systems breathe in antifungal-resistant Aspergillus spores, they could develop infections that are difficult to treat.2 Although few infections caused by azole-resistant Aspergillus fumigatus have been identified in the United States, more infections have been reported in other countries. Aspergillus fumigatus is the most common cause of human Aspergillus infections (both azole-resistant and nonresistant infections).11,12

More research is needed about how Aspergillus becomes resistant and how to protect people from getting resistant Aspergillus infections.

References
  1. Brown GD, Denning DW, Gow NA, Levitz SM, Netea MG, White TC. Hidden killers: human fungal infectionsexternal icon. Sci Transl Med 2012;4:165rv13.
  2. Lestrade PP, Bentvelsen RG, Schauwvlieghe AFAD, Schalekamp S, van der Velden WJFM, Kuiper EJ, et al. Voriconazole resistance and mortality in invasive aspergillosis: a multicenter retrospective cohort studyexternal icon. Clin Infect Dis 2019;68:1463–71.
  3. Baddley JW, Marr KA, Andes DR, Walsh TJ, Kaufman CA, Kontoyiannis DP, et al. Patterns of susceptibility of Aspergillus isolates recovered from patients enrolled in the Transplant-Associated Infection Surveillance Networkexternal icon. J Clin Microbiol 2009;47:3271–5.
  4. Kontoyiannis DP, Marr KA, Park BJ, Alexander BD, Anaissie EJ, Walsh TJ, et al. Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001-2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Databaseexternal icon. Clin Infect Dis 2010;50:1091–100.
  5. Pappas PG, Alexander BD, Andes DR, Hadley S, Kauffman CA, Freifeld A, et al. Invasive fungal infections among organ transplant recipients: results of the Transplant-Associated Infection Surveillance Network (TRANSNET)external icon. Clin Infect Dis 2010;50:1101–11.
  6. Snelders E, Huis in ’t Veld RAG, Rijs AJMM, Kema GHJ, Melchers WJG, Verweij PE. Possible environmental origin of resistance of Aspergillus fumigatus to medical triazolesexternal icon. Appl Environ Microbiol 2009;75:4053–7.
  7. Brauer VS, Rezende CP, Pessoni AM, De Paula RG, Rangappa KS, Nayaka SC, et al. Antifungal agents in agriculture: friends and foes of public healthexternal icon. Biomolecules 2019;9:521.
  8. Hurst SF, Berkow EL, Stevenson KL, Litvintseva AP, Lockhart SR. Isolation of azole-resistant Aspergillus fumigatus from the environment in the south-eastern USAexternal icon. J Antimicrob Chemother 2017;72:2443–6.
  9. Snelders E, Camps SMT, Karawajczyk A, Schaftenaar G, Kema GHJ, van der Lee HA, et al. Triazole fungicides can induce cross-resistance to medical triazoles in Aspergillus fumigatusexternal icon. PLoS One 2012;7:e31801.
  10. Verweij PE, Kema GH, Zwaan B, Melchers WJ. Triazole fungicides and the selection of resistance to medical triazoles in the opportunistic mould Aspergillus fumigatusexternal icon. Pest Manag Sci 2013;69:165–70.
  11. Berkow EL, Nunnally NS, Bandea A, Kuykendall R, Beer K, Lockart SR. Detection of TR34/L98H CYP51A mutation through passive surveillance for azole-resistant Aspergillus fumigatus in the United States from 2015 to 2017external icon. Antimicrob Agents Chemother 2018;62:e02240–17.
  12. Beer KD, Farnon EC, Jain S, Jamerson C, Lineberger S, Miller J, et al. Multidrug-resistant Aspergillus fumigatus carrying mutations linked to environmental fungicide exposure — three states, 2010–2017. MMWR Morb Mortal Wkly Rep 201;67:1064–7.