Systemic candidiasis is generally a disease related to modern medical therapy. As such it is primarily seen in patients who are or have been recently hospitalized and have medical devices present, such as intravascular catheters, or patients who have immune compromise. Injection drug use is an emerging risk factor for community-onset candidemia.[1]Zhang AY, Shrum S, Williams S, et al. The changing epidemiology of candidemia in the United States: injection drug use as an increasingly common risk factor-active surveillance in selected sites, United States, 2014-2017. Clin Infect Dis. 2020 Oct 23;71(7):1732-7.
https://academic.oup.com/cid/article/71/7/1732/5611077?login=false
http://www.ncbi.nlm.nih.gov/pubmed/31676903?tool=bestpractice.com
Candidemia is a growing global concern in terms of both burden of disease and antimicrobial resistance. There are an estimated 25,000 cases of candidemia in the US each year, and it is one of the most common nosocomial bloodstream infections in the US and Europe.[2]Pappas PG. Invasive candidiasis. Infect Dis Clin North Am. 2006 Sep;20(3):485-506.
http://www.ncbi.nlm.nih.gov/pubmed/16984866?tool=bestpractice.com
[3]Tsay SV, Mu Y, Williams S, et al. Burden of candidemia in the United States, 2017. Clin Infect Dis. 2020 Dec 3;71(9):e449-53.
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http://www.ncbi.nlm.nih.gov/pubmed/32107534?tool=bestpractice.com
[4]Lamoth F, Lockhart SR, Berkow EL, et al. Changes in the epidemiological landscape of invasive candidiasis. J Antimicrob Chemother. 2018 Jan 1;73(suppl_1):i4-13.
https://academic.oup.com/jac/article/73/suppl_1/i4/4769692?login=false
http://www.ncbi.nlm.nih.gov/pubmed/29304207?tool=bestpractice.com
Candidemia only represents a portion of systemic candidiasis burden, however. Studies from the Leading International Fungal Education portal estimate the global burden of invasive candidiasis to be 700,000 cases worldwide with rates varying by country (2 to 21 cases per 100,000).[5]Bongomin F, Gago S, Oladele RO, et al. Global and multi-national prevalence of fungal diseases-estimate precision. J Fungi (Basel). 2017 Oct 18;3(4):57.
https://www.mdpi.com/2309-608X/3/4/57
http://www.ncbi.nlm.nih.gov/pubmed/29371573?tool=bestpractice.com
Candida species are highlighted as urgent and serious threats in the US Center for Disease Control and Prevention's 2019 Antibiotic Resistance Threats in the US, and critical and high priority groups in the World Health Organization's 2022 fungal priority pathogens list.[6]Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States, 2019. Dec 2019 [internet publication].
https://www.cdc.gov/drugresistance/biggest-threats.html
[7]World Health Organization. WHO fungal priority pathogens list to guide research, development and public health action. 2022 [internet publication].
https://www.who.int/publications/i/item/9789240060241
Nearly all systemic candidiasis is caused by 5 species: Candida albicans, C glabrata, C parapsilosis, C krusei and C tropicalis. C albicans is the most common species causing infection. However, its relative contribution is declining, and nonalbicans species now account for two-thirds of candidemia cases in the US.[3]Tsay SV, Mu Y, Williams S, et al. Burden of candidemia in the United States, 2017. Clin Infect Dis. 2020 Dec 3;71(9):e449-53.
https://academic.oup.com/cid/article/71/9/e449/5763102?login=false
http://www.ncbi.nlm.nih.gov/pubmed/32107534?tool=bestpractice.com
[8]Horn DL, Neofytos D, Anaissie EJ, et al. Epidemiology and outcomes of candidemia in 2019 patients: data from the prospective antifungal therapy alliance registry. Clin Infect Dis. 2009 Jun 15;48(12):1695-703.
http://www.ncbi.nlm.nih.gov/pubmed/19441981?tool=bestpractice.com
Studies from the SENTRY Antimicrobial Surveillance Program (1997 to 2016) have noted a decline in C albicans to less than half of total isolates causing candidemia.[9]Pfaller MA, Diekema DJ, Turnidge JD, et al. Twenty years of the SENTRY Antifungal Surveillance Program: results for candida species from 1997-2016. Open Forum Infect Dis. 2019 Mar;6(suppl 1):S79-94.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419901
http://www.ncbi.nlm.nih.gov/pubmed/30895218?tool=bestpractice.com
There is wide global variation in the predominance of particular species, with C tropicalis common in South America and Southeast Asia, and C parapsilosis common in Europe.[10]Colombo AL, Nucci M, Park BJ, et al. Epidemiology of candidemia in Brazil: a nationwide sentinel surveillance of candidemia in eleven medical centers. J Clin Microbiol. 2006 Aug;44(8):2816-23.
http://www.ncbi.nlm.nih.gov/pubmed/16891497?tool=bestpractice.com
[11]Chai YA, Wang Y, Khoo AL, et al. Predominance of Candida tropicalis bloodstream infections in a Singapore teaching hospital. Med Mycol. 2007 Aug;45(5):435-9.
http://www.ncbi.nlm.nih.gov/pubmed/17654270?tool=bestpractice.com
[12]Almirante B, Rodriguez D, Cuenca-Estrella M, et al. Epidemiology, risk factors, and prognosis of Candida parapsilosis bloodstream infections: case-control population-based surveillance study of patients in Barcelona, Spain, from 2002 to 2003. J Clin Microbiol. 2006 May;44(5):1681-5.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1479182
http://www.ncbi.nlm.nih.gov/pubmed/16672393?tool=bestpractice.com
In addition to the changing epidemiology of Candida species, decreased mortality has also been observed.[13]Diekema D, Arbefeville S, Boyken L, et al. The changing epidemiology of healthcare-associated candidemia over three decades. Diagn Microbiol Infect Dis. 2012 May;73(1):45-8.
http://www.ncbi.nlm.nih.gov/pubmed/22578938?tool=bestpractice.com
The increase in nonalbicans species is particularly concerning as these species are more likely to be resistant to fluconazole, the mainstay of systemic candidiasis treatment and prophylaxis in much of the world.
In 2016, the US Centers for Disease Control and Prevention issued an alert about the global emergence of the multidrug-resistant species C auris. A number of US states have reported patients with C auris infection, including individuals recently hospitalized in countries with ongoing C auris transmission.[14]Centers for Disease Control and Prevention. Tracking Candida auris. Feb 2023 [internet publication].
https://www.cdc.gov/fungal/candida-auris/tracking-c-auris.html
In 2021 in the European Union and European Economic Area, there were 655 reported cases of C auris.[15]Kohlenberg A, Monnet DL, Plachouras D, et al. Increasing number of cases and outbreaks caused by Candida auris in the EU/EEA, 2020 to 2021. Euro Surveill. 2022 Nov;27(46):2200846.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9673237
http://www.ncbi.nlm.nih.gov/pubmed/36398575?tool=bestpractice.com
Hospitals are advised to identify all invasive Candida isolates to species level in order to institute specific infection control measures when C auris is isolated.[16]Centers for Disease Control and Prevention. Candida auris: information for laboratorians and health professionals. Jul 2021 [internet publication].
https://www.cdc.gov/fungal/candida-auris/health-professionals.html
These include contact precautions, often for prolonged periods if colonization persists, and cleaning and disinfecting the patient care environment with products effective against Clostridium difficile spores, as standard disinfectants may not eradicate the organism.[16]Centers for Disease Control and Prevention. Candida auris: information for laboratorians and health professionals. Jul 2021 [internet publication].
https://www.cdc.gov/fungal/candida-auris/health-professionals.html