Fungal infections that are resistant to treatment are a public health challenge. We all have a role in preventing these infections and reducing antifungal resistance.
Antifungal drugs and antibiotics are both types of antimicrobials, meaning that they kill or stop the growth of microscopic organisms. Antifungal drugs save lives by treating dangerous fungal infections, just like antibiotics are used to treat bacterial infections. Unfortunately, fungi and bacteria can develop the ability to spread and grow despite being exposed to the drugs designed to kill them. This is known as antimicrobial resistance. When fungi no longer respond to antifungal drugs, it is called antifungal resistance. This resistance is especially concerning for patients with invasive fungal infections that affect the blood, heart, brain, eyes or other parts of the body. For example, bloodstream infections with the fungus Candida (a yeast) that are resistant to treatment can cause serious health problems, including disability and death.
More information is needed about the risk antifungal resistance poses to human health and how many people are sickened by drug-resistant fungal infections each year. CDC and its partners are working to:
- Better understand why and how antifungal resistance emerges.
- Increase awareness among medical and public health communities about these infections.
- Develop better methods to prevent and control drug-resistant fungal infections.
Fungal infections are a serious problem in healthcare settings
Invasive fungal infections can cause disability and death. Patients can get fungal infections while receiving care for another condition in a healthcare facility. For example, the fungus Candida is a leading cause of healthcare-associated bloodstream infections in U.S. hospitals.1 These infections are also costly for patients and healthcare facilities. Each case of Candida bloodstream infection (also known as candidemia) is estimated to result in an additional 3 to 13 days of hospitalization and $6,000 to $29,000 in healthcare costs.2 Although antifungals can be used to treat most candidemia, some types of Candida are increasingly resistant to the antifungal medications most commonly used for treatment, such as the echinocandins (anidulafungin, caspofungin, and micafungin) and fluconazole.
Antifungal resistance makes infections harder to treat
Antifungal resistance is a particular problem with Candida infections. About 7% of all Candida bloodstream isolates (pure samples of a germ) tested at CDC are resistant to fluconazole. Although Candida albicans is the most common cause of severe Candida infections, resistance is most common in other species, particularly Candida glabrata and Candida parapsilosis.3
CDC’s surveillance data indicate that the proportion of Candida isolates that are resistant to fluconazole has remained fairly constant over the past 20 years.3-6 Echinocandin resistance, however, appears to be emerging, especially among Candida glabrata isolates. CDC’s surveillance data indicate that approximately 3% of Candida glabrata isolates are resistant to echinocandins. This is especially concerning as echinocandins are the preferred treatment for Candida glabrata, which already has high levels of resistance to fluconazole.3
Multidrug-resistant Candida infections (those that are resistant to both fluconazole and an echinocandin) have very few remaining treatment options. The primary treatment option is Amphotericin B, a drug that can be toxic for patients who are already very sick. Growing evidence suggests that patients who have drug-resistant candidemia are less likely to survive than patients who have candidemia that can be treated by antifungal medications.6,7 We must act to prevent further resistance from developing and to prevent the spread of these infections. Antifungal resistance is already a problem in the more common Candida species described above, but it is an even bigger concern for the emerging fungus Candida auris,8 (C. auris) which is rare in the United States but is a growing threat. Resistance rates are much higher than for other Candida species, with about 90% [or most] of C. auris isolates sent to CDC being resistant to fluconazole and up to one-third resistant to amphotericin B.9 Most C. auris isolates are susceptible to echinocandins. However, echinocandin resistance can develop while the patient is being treated. C. auris is also a concerning public health issue because it can be difficult to identify with standard laboratory methods and because it spreads easily in healthcare settings, such as hospitals and long-term care facilities.
Antifungal resistance in Aspergillus
Although the most common antifungal resistance occurs in Candida species, resistance in other types of less common fungi is also a problem. In Aspergillus (a mold) infections, emerging resistance to the preferred treatment threatens the effectiveness of life-saving medicine.
Aspergillus infections can cause life-threatening illness in people with weakened immune systems, underlying diseases, or transplant patients. Aspergillus is the leading cause of invasive mold infections, with an estimated 200,000 cases worldwide every year.10 The preferred treatments for these infections are voriconazole and certain other azole drugs. However, in some areas, 12% of Aspergillus infections are estimated to be resistant to azole medications.11 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.12-14
Resistant Aspergillus infections can develop in people who have taken certain antifungal medicines.15 However, resistant infections are also found in people who have not taken antifungal medicines. This demonstrates that antifungal resistance in Aspergillus is likely acquired before entering the healthcare setting and is partially driven by environmental sources. For example, research shows that treating crop diseases with azole fungicides, which are similar to azole medications like voriconazole, can lead to the growth of resistant strains of Aspergillus in soil and other places in the environment.16,17 If people with weakened immune systems breathe in antifungal-resistant Aspergillus spores, then they could develop infections that are difficult to treat.17 Although few infections caused by azole-resistant A. fumigatus have been identified in the United States, many more infections have been reported in other countries. More research is needed about how Aspergillus becomes resistant and how to prevent people from getting resistant Aspergillus infections.
Some species of fungi are naturally resistant to treatment with certain types of antifungal drugs. Other species can develop resistance over time. Resistance can develop from improper antifungal use to treat sick people —for example, dosages too low or treatment courses that are not long enough.18,19 Use of fungicides in agriculture to prevent and treat fungal diseases in crops can also contribute to resistance.
Some studies have indicated that antibiotic drugs may also contribute to antifungal resistance. This resistance could occur for a variety of reasons. For example, antibiotics can reduce good and bad bacteria in the gut, which creates favorable conditions for Candida growth.20 It is not known if decreasing the use of all or certain antibiotics can reduce Candida infections, but appropriate use of antibiotics and antifungal medications is one of the most important factors in fighting drug resistance.
Antifungal resistance is a growing threat. Everyone has a role to play in preventing fungal infections and reducing antifungal resistance.
- CDC is:
- Tracking trends in antifungal resistance through the Emerging Infections Program (EIP ) by conducting multicenter candidemia surveillance and performing species confirmation and antifungal susceptibility testing on Candida bloodstream isolates. CDC is also conducting limited EIP surveillance for Aspergillus and other invasive mold infections.
- Supporting a network of regional public health laboratories through the Antibiotic Resistance Laboratory Network (ARLN) to perform antifungal susceptibility testing for Candida. These labs also help identify C. auris and perform testing of patient swabs for C. auris colonization, a key step in containing its spread.
- Using genetic sequencing and developing new laboratory tests to identify and understand specific mutations associated with antifungal resistance in Candida.
- Summarizing antifungal prescribing patterns across different healthcare facilities to understand opportunities to promote appropriate use of antifungals.
- Healthcare facility executives and infection control staff can:
- Assess antifungal use as part of their antibiotic stewardship programs.
- Ensure adherence to guidelines for hand hygiene, prevention of catheter-associated infections, and environmental infection control.
- Doctors and other hospital staff can:
- Prescribe antifungal medications appropriately.
- Test for antifungal resistance for patients with invasive disease who are not improving with first-line antifungal medications.21,22
- Stay aware of resistance patterns, including antifungal resistance, in your facility and community.
- Document the dose, duration, and indication for every antifungal prescription.
- Participate in and lead efforts within your hospital to improve antifungal prescribing practices.
- Follow hand hygiene and other infection prevention and control guidelines with every patient.
- Hospital patients can:
- Clean your hands.
- Be sure everyone cleans their hands before entering your room.
- If you have a catheter, ask each day if it is necessary.
- Talk to your healthcare provider about your risk for certain infections, especially if you have a weakened immune system.
Everyone can help slow down antifungal resistance by only taking antifungals when needed and taking them exactly as prescribed. Talk to your doctor if you experience side effects or if the antifungal you are taking is not treating symptoms.
- CDC Expert Commentary on Medscape: The Rise in Antifungal Resistanceexternal icon
- CDC – Antibiotic Resistance Threats in the United States, 2019 pdf icon[PDF – 148 pages]
- CDC – Candida auris
- CDC – Antimicrobial Resistance
- CDC – Checklist for Core Elements of Hospital Antibiotic Stewardship Programs pdf icon[PDF – 4 pages]
- CDC – Hand Hygiene in Healthcare Settings
- CDC – Central Line-associated Bloodstream Infection (CLABSI)
- The White House – National Strategy for Combating Antibiotic-Resistant Bacteria pdf icon[PDF – 37 pages]external icon
- Magill SS, Edwards JR, Bamberg W, et al. Multistate point-prevalence survey of health care-associated infections. The New England journal of medicine 2014;370:1198-208.
- Morgan J, Meltzer MI, Plikaytis BD, et al. Excess mortality, hospital stay, and cost due to candidemia: a case-control study using data from population-based candidemia surveillance. Infection control and hospital epidemiology 2005;26:540-7.
- Toda M, Williams SR, Berkow EL, et al. Population-Based Active Surveillance for Culture-Confirmed Candidemia — Four Sites, United States, 2012–2016. MMWR Surveill Summ 2019;68(No. SS-8):1–15. DOI: http://dx.doi.org/10.15585/mmwr.ss6808a1external icon.
- Hajjeh RA, Sofair AN, Harrison LH, et al. Incidence of bloodstream infections due to Candida species and in vitro susceptibilities of isolates collected from 1998 to 2000 in a population-based active surveillance program. Journal of clinical microbiology 2004;42:1519-27.
- Kao AS, Brandt ME, Pruitt WR, et al. The epidemiology of candidemia in two United States cities: results of a population-based active surveillance. Clinical infectious diseases 1999;29:1164-70.
- Alexander BD, Johnson MD, Pfeiffer CD, et al. Increasing echinocandin resistance in Candida glabrata: clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations. Clinical infectious diseases 2013;56:1724-32.
- Baddley JW, Patel M, Bhavnani SM, Moser SA, Andes DR. Association of fluconazole pharmacodynamics with mortality in patients with candidemia. Antimicrobial agents and chemotherapy 2008;52:3022-8.
- Satoh K, Makimura K, Hasumi Y, Nishiyama Y, Uchida K, Yamaguchi H. Candida auris sp. nov., a novel ascomycetous yeast isolated from the external ear canal of an inpatient in a Japanese hospital. Microbiol Immunol 2009;53:41-4.
- Lockhart SR, Etienne KA, Vallabhaneni S, et al. Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2017;64:134-40.
- Brown GD, Denning DW, Gow NA, Levitz SM, Netea MG, White TC. Hidden killers: human fungal infections. Sci Transl Med 2012;4:165rv13.
- Rivero-Menendez O, Alastruey-Izquierdo A, Mellado E, Cuenca-Estrella M. Triazole Resistance in Aspergillus spp.: A Worldwide Problem? J Fungi (Basel) 2016;2.
- Baddley JW, Marr KA, Andes DR, et al. Patterns of susceptibility of Aspergillus isolates recovered from patients enrolled in the Transplant-Associated Infection Surveillance Network. Journal of clinical microbiology 2009;47:3271-5.
- Kontoyiannis DP, Marr KA, Park BJ, 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) Database. Clinical Infectious Diseases 2010;50:1091-100.
- Pappas PG, Alexander BD, Andes DR, et al. Invasive fungal infections among organ transplant recipients: results of the Transplant-Associated Infection Surveillance Network (TRANSNET). Clinical Infectious Diseases 2010;50:1101-11.
- Howard SJ, Cerar D, Anderson MJ, et al. Frequency and evolution of Azole resistance in Aspergillus fumigatus associated with treatment failure. Emerging infectious diseases 2009;15:1068-76.
- Mortensen KL, Mellado E, Lass-Florl C, Rodriguez-Tudela JL, Johansen HK, Arendrup MC. Environmental study of azole-resistant Aspergillus fumigatus and other aspergilli in Austria, Denmark, and Spain. Antimicrobial agents and chemotherapy 2010;54:4545-9.
- Verweij PE, Snelders E, Kema GH, Mellado E, Melchers WJ. Azole resistance in Aspergillus fumigatus: a side-effect of environmental fungicide use? Lancet Infect Dis 2009;9:789-95.
- Lortholary O, Desnos-Ollivier M, Sitbon K, et al. Recent exposure to caspofungin or fluconazole influences the epidemiology of candidemia: a prospective multicenter study involving 2,441 patients. Antimicrobial agents and chemotherapy 2011;55:532-8.
- Shah DN, Yau R, Lasco TM, et al. Impact of prior inappropriate fluconazole dosing on isolation of fluconazole-nonsusceptible Candida species in hospitalized patients with candidemia. Antimicrobial agents and chemotherapy 2012;56:3239-43.
- Ben-Ami R, Olshtain-Pops K, Krieger M, et al. Antibiotic exposure as a risk factor for fluconazole-resistant Candida bloodstream infection. Antimicrobial agents and chemotherapy 2012;56:2518-23.
- Patterson TF, Thompson GR, 3rd, Denning DW, et al. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis 2016;63:e1-e60.
- Pappas PG, Kauffman CA, Andes DR, et al. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2016;62:e1-50.