Invasive candidiasis

Kullberg, Bart Jan; Arendrup, Maiken C.

doi:10.1056/nejmra1315399

Cited by 1,315Antifungal resistance and susceptibilityFungal Infections and StudiesOcular Infections and Treatments

Invasive candidiasis

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Kullberg, Bart Jan, Arendrup, Maiken C.·2015·New England Journal of Medicine

DOI 10.1056/nejmra1315399

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Abstract

Despite advances in antifungal therapy, the mortality associated with invasive candidiasis remains as high as 40%. This review summarizes recent trends and current strategies, including early treatment and the emergence of resistance against triazoles and echinocandins.

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Crossref · 10.1056/nejmra1315399

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Other studies did not observe an association between antimicrobial timing and mortality.
“Other studies, however, did not observe an association between antimicrobial timing and mortality (112-117).”
From Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. (2021) · cites this paper as [116]
The Early Treatment section says retrospective studies associated early antifungal therapy with reduced mortality and that adjusted analyses consistently identified early appropriate therapy as a major determinant of survival. It cautions that early presumptive-treatment strategies have not been validated prospectively, but does not report studies finding no association between treatment timing and mortality. (LLM, conf=0.86)
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A review of the most recent data suggests that many, but not all, breakthrough Candida infections occur due to organisms that are resistant to one or more antifungals, and are dominated by non-albicans Candida species, especially C. glabrata, C. krusei, C. parapsilosis, and C. tropicalis.
“A review of the most recent data pertaining to BT Candida infections suggests that many, but not all, of these infections occur due to organisms that are resistant to one or more antifungals, and accordingly are dominated by non-albicans Candida species, especially C. glabrata, C. krusei, C. parapsilosis, and C. tropicalis.89–92”
From Epidemiology of Invasive Candidiasis (2024) · cites this paper as [92]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured
Candidaemia is the most common form of invasive candidiasis and is associated with mortality in excess of 40% even with newer antifungal agents.
“Candidaemia is the most common form of invasive candidiasis associated with an unacceptably high mortality rates in excess of 40% even with the introduction of newer antifungal agents [30,32,33].”
From Global and Multi-National Prevalence of Fungal Diseases-Estimate Precision (2017) · cites this paper as [33]
The Abstract describes candidemia as generally the more common form of invasive candidiasis. It reports mortality as high as 40% among patients with invasive candidiasis despite antifungal therapy, but does not establish mortality in excess of 40% specifically for candidemia or despite newer agents. (LLM, conf=0.90)
Experimental — accuracy not yet measured
Invasive Candida spp. infections are an increasing concern among US healthcare facilities, as candidemia ranks in the top 4 hospital-associated bloodstream infections in the country.
“Invasive Candida spp. infections are an increasing concern among US healthcare facilities, as candidemia ranks in the top 4 hospital-associated bloodstream infections in the country [1].”
From Invasive candidiasis species distribution and trends, United States, 2009-2017 (2021) · cites this paper as [1]
The Epidemiology passage (labeled Abstract in our copy; page not provided) says candidemia has often been cited as the fourth most common bloodstream infection, but explicitly limits that ranking to intensive care units. It reports seventh to tenth place in most population-based studies, so it does not support a top-four ranking across US healthcare facilities. It also says incidence has increased or remained stable in most regions, while declining in some high-incidence areas. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Recent abdominal surgery, disruption of the microbiome from antibiotics, receipt of total parental nutrition (TPN), diabetes, malignancies, neutropenia, use of immunosuppressive therapies, and presence of indwelling catheters such as central venous catheters (CVCs) and other devices are all risk factors for candidemia.
“Recent abdominal surgery and other medical interventions, disruption of the microbiome from antibiotics, receipt of total parental nutrition (TPN), diabetes, malignancies, neutropenia, use of immunosuppressive therapies, and presence of indwelling catheters such as central venous catheters (CVCs) and other devices (8–10) are all risk factors for candidemia.”
From Population-Based Active Surveillance for Culture-Confirmed Candidemia — Four Sites, United States, 2012–2016 (2019) · cites this paper as [10]
The risk-factor discussion (page not specified) identifies recent abdominal surgery, broad-spectrum antibiotics, and central vascular catheters; Table 1 also lists total parenteral nutrition, malignancies, and glucocorticoid use or cancer chemotherapy. The cited passages do not identify diabetes, neutropenia, or other indwelling devices as risk factors, so they do not support the entire list. (LLM, conf=0.87)
Experimental — accuracy not yet measured

Neutropenia, hematologic malignancies, and bone marrow transplants are well-recognized risk factors for candidemia.
“Although neutropenia (53,54), hematologic malignancies (53), and bone marrow transplants (10,13) are well-recognized risk factors for candidemia”
From Population-Based Active Surveillance for Culture-Confirmed Candidemia — Four Sites, United States, 2012–2016 (2019) · cites this paper as [10]
Table 1 (page not given) lists hematologic malignant disease as a risk factor for invasive candidiasis, which includes candidemia. It lists solid-organ transplantation, not bone marrow transplantation, and does not list neutropenia as a risk factor. The paper therefore supports only the hematologic-malignancy part of the claim. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Additional candidemia risk factors include malignancies, hemodialysis, diabetes, and receipt of immunosuppressive medications (including corticosteroids); total parenteral nutrition; and systemic antibacterial medications.
“Additional candidemia risk factors include malignancies, hemodialysis, diabetes, and receipt of immunosuppressive medications (including corticosteroids); total parenteral nutrition; and systemic antibacterial medications (7).”
From Population-Based Active Surveillance for Culture-Confirmed Candidemia — 10 Sites, United States, 2017–2021 (2025) · cites this paper as [7]
Table 1 (Risk Factors for Invasive Candidiasis) lists hematologic malignancy, solid-organ tumors, hemodialysis, glucocorticoid use or cancer chemotherapy, total parenteral nutrition, and broad-spectrum antibiotics. It does not list diabetes, and its specified drug exposures do not establish a risk from immunosuppressive medications or systemic antibacterials generally. (LLM, conf=0.88)
Experimental — accuracy not yet measured
The infection might develop after translocation of Candida spp. from the gut through disruptions in the intestinal mucosa, making abdominal surgeries a candidemia risk factor.
“The infection might develop after translocation of Candida spp. from the gut through disruptions in the intestinal mucosa, making abdominal surgeries a candidemia risk factor (7).”
From Population-Based Active Surveillance for Culture-Confirmed Candidemia — 10 Sites, United States, 2017–2021 (2025) · cites this paper as [7]
The incidence rate of candidiasis has been estimated at two to 14 cases per 100,000 inhabitants.
“Population-based studies have estimated the incidence rate of candidiasis to be two to 14 cases per 100,000 inhabitants”
From Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens (2018) · cites this paper as [4]
Candidemia affects more than 250,000 persons worldwide every year and leads to more than 50,000 deaths.
“candidemia (Candida bloodstream infection) affects more than 250,000 persons worldwide every year, leading to more than 50,000 deaths [4].”
From Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens (2018) · cites this paper as [4]
Hematologic malignancy is a risk factor for candidemia.
“Hematologic malignancy is a risk factor for candidemia.1”
From Distribution, trends, and antifungal susceptibility ofCandidaspecies causing candidemia in Japan, 2010–2019: A retrospective observational study based on national surveillance data (2022) · cites this paper as [1]

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[1]1. Arendrup MC. Epidemiology of inva- sive candidiasis. Curr Opin Crit Care 2010; 16: 445-52.
[32]32. Muldoon EG, Denning DW. Prophy- lactic echinocandin: is there a subgroup of intensive care unit patients who bene- fit? Clin Infect Dis 2014; 58: 1227-9.
[62]62. Arendrup MC, Perlin DS. Echinocan- din resistance: an emerging clinical prob- lem? Curr Opin Infect Dis 2014; 27: 484-92.

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“tropicalis 120 (8) 107 (11) 17 (5) 48 (10) 292 (9)”
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An Update on the Roles of Non-albicans Candida Species in Vulvovaginitis
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Intra-Abdominal Candidiasis: The Importance of Early Source Control and Antifungal Treatment
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“92 Less common species such as C. lusitaniae and C. guilliermondii have also been reported.”
Background
Strategies to Reduce Mortality in Adult and Neonatal Candidemia in Developing Countries
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Candida albicans exhibits heterogeneous and adaptive cytoprotective responses to antifungal compounds
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Authors: Kullberg, B. J., & Arendrup, M. C.
Affiliations: Radboud University Medical Center (NL)
Statens Serum Institut (DK)
ORCID: Kullberg, Bart Jan
Arendrup, Maiken C.
Venue: New England Journal of Medicine
Publisher: Massachusetts Medical Society
Published: 2015-10-08
Volume: 373
Issue: 15
Pages: 1445-1456
ISSN: 0028-4793 (ISSN-L)
1533-4406
DOI: 10.1056/nejmra1315399
OpenAlex: W4253534765
Semantic Scholar: ff44b0436275e8511a64e887cdde44a9a8d25389
Cited by: 1,315
References: 64
Citations by year: 2026: 107 · 2025: 127 · 2024: 106 · 2023: 134 · 2022: 147 · 2021: 154 · 2020: 148 · 2019: 116 · 2018: 110 · 2017: 105 · 2016: 57 · 2015: 3
FWCI: 13.92
Type: journal article
Language: en
Open access: green
hdl.handle.net
Locations: New England Journal of Medicine (publishedVersion)
PubMed (publishedVersion)
Radboud Repository (Radboud University) (submittedVersion)
Radboud Repository (Radboud University) (submittedVersion, other-oa)
Topics: Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
Health Sciences › Medicine › Ophthalmology › Ocular Infections and Treatments
Keywords: invasive candidiasis, antifungal therapy, mortality, early treatment, triazole resistance, echinocandin resistance, Candida
MeSH terms: Antifungal Agents, Candida, Humans, Drug Resistance, Fungal, Catheter-Related Infections, Candidiasis, Invasive

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