Epidemiology and pathogenesis of candidemia in adults
- Carol A Kauffman, MD
Carol A Kauffman, MD
- Section Editor — Fungal Infections
- Professor of Internal Medicine
- University of Michigan Medical School
- Veterans Affairs Ann Arbor Healthcare System
The term candidemia describes the presence of Candida species in the blood. Candida in a blood culture should never be viewed as a contaminant and should always prompt a search for the source of infection. For many patients, candidemia is a manifestation of disseminated candidiasis, whereas for others it reflects colonization of an indwelling intravenous catheter .
Clinical issues related to the epidemiology and pathogenesis of candidemia will be reviewed here. The clinical manifestations, diagnosis, and treatment of candidemia as well as an overview of Candida infections are presented separately. (See "Clinical manifestations and diagnosis of candidemia and invasive candidiasis in adults" and "Treatment of candidemia and invasive candidiasis in adults" and "Overview of Candida infections".)
Candidiasis is an increasingly important nosocomial infection in both adults and children, especially those who are cared for in intensive care units (ICUs) [2-11]. (See "Epidemiology, pathogenesis, and microbiology of intravascular catheter infections" and "Epidemiology of surgical site infection in adults".)
Although the infecting strain is most often part of the host's endogenous flora, nosocomial acquisition of Candida species has been described . The organism has spread via contaminated solutions in some cases , whereas the hands of healthcare workers were the probable source in others.
Prevalence of Candida species — Although C. albicans is the most common cause of candidemia, there has been increased isolation of non-albicans species of Candida in recent years [12-18]. In a multicenter surveillance study conducted in the United States between 2004 and 2008, 54 percent of 2019 bloodstream isolates represented non-albicans Candida spp and 46 percent represented C. albicans . C. glabrata was responsible for 26 percent of all cases of candidemia, followed by C. parapsilosis (16 percent), C. tropicalis (8 percent), and C. krusei (3 percent). Other studies have shown a similar order of frequency, although the incidence of each species varies in different patient populations and geographic regions [16,19-23]. As an example, in Latin America, the most common species to cause bloodstream infection after C. albicans are C. parapsilosis and C. tropicalis, with C. glabrata being isolated much less frequently [19,21,22].
- Fridkin SK. The changing face of fungal infections in health care settings. Clin Infect Dis 2005; 41:1455.
- Wisplinghoff H, Bischoff T, Tallent SM, et al. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 2004; 39:309.
- Chow JK, Golan Y, Ruthazer R, et al. Risk factors for albicans and non-albicans candidemia in the intensive care unit. Crit Care Med 2008; 36:1993.
- Playford EG, Marriott D, Nguyen Q, et al. Candidemia in nonneutropenic critically ill patients: risk factors for non-albicans Candida spp. Crit Care Med 2008; 36:2034.
- Playford EG, Nimmo GR, Tilse M, Sorrell TC. Increasing incidence of candidaemia: long-term epidemiological trends, Queensland, Australia, 1999-2008. J Hosp Infect 2010; 76:46.
- Zaoutis TE, Argon J, Chu J, et al. The epidemiology and attributable outcomes of candidemia in adults and children hospitalized in the United States: a propensity analysis. Clin Infect Dis 2005; 41:1232.
- Arendrup MC, Fuursted K, Gahrn-Hansen B, et al. Semi-national surveillance of fungaemia in Denmark 2004-2006: increasing incidence of fungaemia and numbers of isolates with reduced azole susceptibility. Clin Microbiol Infect 2008; 14:487.
- Pfaller MA, Diekema DJ. Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev 2007; 20:133.
- Kullberg BJ, Arendrup MC. Invasive Candidiasis. N Engl J Med 2015; 373:1445.
- Kollef M, Micek S, Hampton N, et al. Septic shock attributed to Candida infection: importance of empiric therapy and source control. Clin Infect Dis 2012; 54:1739.
- León C, Alvarez-Lerma F, Ruiz-Santana S, et al. Fungal colonization and/or infection in non-neutropenic critically ill patients: results of the EPCAN observational study. Eur J Clin Microbiol Infect Dis 2009; 28:233.
- Malani A, Hmoud J, Chiu L, et al. Candida glabrata fungemia: experience in a tertiary care center. Clin Infect Dis 2005; 41:975.
- Almirante B, Rodríguez 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; 44:1681.
- Messer SA, Jones RN, Fritsche TR. International surveillance of Candida spp. and Aspergillus spp.: report from the SENTRY Antimicrobial Surveillance Program (2003). J Clin Microbiol 2006; 44:1782.
- Trofa D, Gácser A, Nosanchuk JD. Candida parapsilosis, an emerging fungal pathogen. Clin Microbiol Rev 2008; 21:606.
- 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; 48:1695.
- Leroy O, Gangneux JP, Montravers P, et al. Epidemiology, management, and risk factors for death of invasive Candida infections in critical care: a multicenter, prospective, observational study in France (2005-2006). Crit Care Med 2009; 37:1612.
- Lyon GM, Karatela S, Sunay S, et al. Antifungal susceptibility testing of Candida isolates from the Candida surveillance study. J Clin Microbiol 2010; 48:1270.
- Nucci M, Queiroz-Telles F, Tobón AM, et al. Epidemiology of opportunistic fungal infections in Latin America. Clin Infect Dis 2010; 51:561.
- Diekema DJ, Messer SA, Brueggemann AB, et al. Epidemiology of candidemia: 3-year results from the emerging infections and the epidemiology of Iowa organisms study. J Clin Microbiol 2002; 40:1298.
- Pfaller MA, Moet GJ, Messer SA, et al. Geographic variations in species distribution and echinocandin and azole antifungal resistance rates among Candida bloodstream infection isolates: report from the SENTRY Antimicrobial Surveillance Program (2008 to 2009). J Clin Microbiol 2011; 49:396.
- Colombo AL, Guimarães T, Silva LR, et al. Prospective observational study of candidemia in São Paulo, Brazil: incidence rate, epidemiology, and predictors of mortality. Infect Control Hosp Epidemiol 2007; 28:570.
- Fortún J, Martín-Dávila P, Gómez-García de la Pedrosa E, et al. Emerging trends in candidemia: a higher incidence but a similar outcome. J Infect 2012; 65:64.
- Garnacho-Montero J, Díaz-Martín A, García-Cabrera E, et al. Risk factors for fluconazole-resistant candidemia. Antimicrob Agents Chemother 2010; 54:3149.
- Oxman DA, Chow JK, Frendl G, et al. Candidaemia associated with decreased in vitro fluconazole susceptibility: is Candida speciation predictive of the susceptibility pattern? J Antimicrob Chemother 2010; 65:1460.
- 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. Clin Infect Dis 2013; 56:1724.
- Castanheira M, Woosley LN, Messer SA, et al. Frequency of fks mutations among Candida glabrata isolates from a 10-year global collection of bloodstream infection isolates. Antimicrob Agents Chemother 2014; 58:577.
- Lewis JS 2nd, Wiederhold NP, Wickes BL, et al. Rapid emergence of echinocandin resistance in Candida glabrata resulting in clinical and microbiologic failure. Antimicrob Agents Chemother 2013; 57:4559.
- Abbas J, Bodey GP, Hanna HA, et al. Candida krusei fungemia. An escalating serious infection in immunocompromised patients. Arch Intern Med 2000; 160:2659.
- Cuenca-Estrella M, Rodriguez D, Almirante B, et al. In vitro susceptibilities of bloodstream isolates of Candida species to six antifungal agents: results from a population-based active surveillance programme, Barcelona, Spain, 2002-2003. J Antimicrob Chemother 2005; 55:194.
- 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. Antimicrob Agents Chemother 2011; 55:532.
- Lin MY, Carmeli Y, Zumsteg J, et al. Prior antimicrobial therapy and risk for hospital-acquired Candida glabrata and Candida krusei fungemia: a case-case-control study. Antimicrob Agents Chemother 2005; 49:4555.
- Centers for Disease Control and Prevention. Clinical Alert to U.S. Healthcare Facilities - Global Emergence of Invasive Infections Caused by the Multidrug-Resistant Yeast Candida auris. https://www.cdc.gov/fungal/diseases/candidiasis/candida-auris-alert.html (Accessed on July 08, 2016).
- Public Health England. Candida auris identified in England. https://www.gov.uk/government/publications/candida-auris-emergence-in-england/candida-auris-identified-in-england (Accessed on July 08, 2016).
- Satoh K, Makimura K, Hasumi Y, et al. 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.
- Lee WG, Shin JH, Uh Y, et al. First three reported cases of nosocomial fungemia caused by Candida auris. J Clin Microbiol 2011; 49:3139.
- Vallabhaneni S, Kallen A, Tsay S, et al. Investigation of the First Seven Reported Cases of Candida auris, a Globally Emerging Invasive, Multidrug-Resistant Fungus - United States, May 2013-August 2016. MMWR Morb Mortal Wkly Rep 2016; 65:1234.
- 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. Clin Infect Dis 2017; 64:134.
- Tsay S, Welsh RM, Adams EH, et al. Notes from the Field: Ongoing Transmission of Candida auris in Health Care Facilities - United States, June 2016-May 2017. MMWR Morb Mortal Wkly Rep 2017; 66:514.
- Azar MM, Turbett SE, Fishman JA, Pierce VM. Donor-derived transmission of Candida auris during lung transplantation. Clin Infect Dis 2017.
- Chow JK, Golan Y, Ruthazer R, et al. Factors associated with candidemia caused by non-albicans Candida species versus Candida albicans in the intensive care unit. Clin Infect Dis 2008; 46:1206.
- Cohen Y, Karoubi P, Adrie C, et al. Early prediction of Candida glabrata fungemia in nonneutropenic critically ill patients. Crit Care Med 2010; 38:826.
- Hachem R, Hanna H, Kontoyiannis D, et al. The changing epidemiology of invasive candidiasis: Candida glabrata and Candida krusei as the leading causes of candidemia in hematologic malignancy. Cancer 2008; 112:2493.
- Pfaller MA, Diekema DJ, Rinaldi MG, et al. Results from the ARTEMIS DISK Global Antifungal Surveillance Study: a 6.5-year analysis of susceptibilities of Candida and other yeast species to fluconazole and voriconazole by standardized disk diffusion testing. J Clin Microbiol 2005; 43:5848.
- Johnson MD, Plantinga TS, van de Vosse E, et al. Cytokine gene polymorphisms and the outcome of invasive candidiasis: a prospective cohort study. Clin Infect Dis 2012; 54:502.
- Plantinga TS, Johnson MD, Scott WK, et al. Toll-like receptor 1 polymorphisms increase susceptibility to candidemia. J Infect Dis 2012; 205:934.
- Velasco E, Bigni R. A prospective cohort study evaluating the prognostic impact of clinical characteristics and comorbid conditions of hospitalized adult and pediatric cancer patients with candidemia. Eur J Clin Microbiol Infect Dis 2008; 27:1071.