Etiology
Candida species are present as normal flora in the gastrointestinal (GI) tract of humans and can also colonize the skin and urogenital tract. Therefore, systemic candidiasis often has an endogenous source of infection, primarily the GI tract. Although mucocutaneous disease is common, invasive disease is not, and the primary reason is that Candida species in general are unable to traverse intact epithelium. Candida glabrata and Candida tropicalis are known to colonize the GI tract, whereas Candida parapsilosis tends to colonize skin and intravascular catheters. C parapsilosis can also be found on the hands of healthcare workers.
Common Candida species associated with candidemia and systemic candidiasis include:
C albicans
C glabrata (reclassified as Nakaseomyces glabrata)
C tropicalis
C parapsilosis
C dubliniensis
C krusei (Pichia kudriavzevii)
C kefyr (Kluyveromyces marxianus)
C lusitaniae (Clavispora lusitaniae)
C auris (Candidozyma auris)
Due to some clades better fitting the definition of a genus, some Candida species have undergone reclassification in recent years resulting in new nomenclatures as reflected above.[1] Within this topic, the traditional nomenclature is currently used elsewhere, given that clinical adoption of the revised nomenclature is in its early stages.
Pathophysiology
Candida species have specific receptors that assist in binding to mucosal surfaces and endothelial cells, enabling bloodstream dissemination.[3][20] The primary event in the transition from superficial infection to systemic, invasive infection or colonization is a disruption of the epithelial barrier, usually through insertion of an intravascular catheter, indwelling urinary catheter or other foreign material or device. Other routes of infection include disruption of the gut mucosa, for instance through ulceration due to chemotherapy in patients with neutropenia and, rarely, from focal infections such as pyelonephritis secondary to an ascending urinary tract infection. The alteration of normal flora by administration of broad-spectrum antibiotics allows the yeast to proliferate in high numbers during invasion.
Candida can form biofilms which allow persistence of the fungus and possibly contribute to antifungal resistance. Weakening of the immune system also contributes to the development of infection. T lymphocytes, including T helper 17 cells, play a role in preventing mucosal disease. Plasma cells can produce antibodies targeting Candida which results in the formation of immune complexes that can be opsonized to clear the infection. Innate immunity through phagocytes including neutrophils, monocytes, macrophages, and dendritic cells contribute to host protection against invasive infection. In particular, toll-like receptors (TLRs including TLR2 and TLR4) and C-type lectin receptors (CLRs) on the surface of these cells recognize conserved microbial products known as Pathogen Associated Molecular Patterns (PAMPs), such as glucans, of the Candida species.[3][20][21][22]
Virulence factors vary between different Candida species and include the ability to undergo morphogenic changes as well as secretion of proteases and phospholipases.
Use of this content is subject to our disclaimer