Invasive Candidiasis

Infectious Disease MONDO:0044067 Pathograph 12 Show in embeddings browser Candidiasis Invasive fungal infection

Invasive candidiasis is infection by Candida species in a normally sterile body compartment. Candidemia, in which Candida is recovered from the bloodstream, is its most common named form. The entry focuses narrowly on the conserved fungal-cell-wall target that explains why echinocandins are used: Fks glucan synthase, encoded principally by FKS1 with FKS2 additionally relevant in species such as Candida glabrata, produces beta-1,3-glucan, and anidulafungin inhibits that enzyme to compromise the Candida cell wall.

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4
Pathophys.
5
Phenotypes
12
Pathograph
1
Medical Actions
1
Subtypes
🏷

Classifications

Harrison's Part
INFECTIOUS DISEASES
◆

Subtypes

1
Candidemia MONDO:0044070
Bloodstream infection with Candida species; candidemia is a form of invasive candidiasis and the principal clinical setting represented by the echinocandin evidence in this entry.
Show evidence (1 reference)
PMID:36135696 SUPPORT Human Clinical
"Bloodstream infections caused by Candida yeasts (candidemia) are associated with high morbidity and mortality."
Defines candidemia as Candida bloodstream infection and supports it as an invasive-candidiasis subtype.
⚙

Pathophysiology

4
Candida beta-1,3-Glucan Synthesis by Fks Glucan Synthase
The Candida plasma-membrane glucan-synthase complex uses the catalytic subunit encoded principally by FKS1; FKS2 supplies additional catalytic capacity in species such as Candida glabrata. The complex synthesizes beta-1,3-glucan, an essential structural polymer of the fungal cell wall. This fungus-specific activity is the direct therapeutic vulnerability inhibited by echinocandins. The node is intentionally target-only: it does not assert that normal wall synthesis positively causes the intervention-conditional wall failure that follows pharmacologic inhibition.
beta-1,3-Glucan Biosynthesis GO:0006075 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves beta-1,3-Glucan Biosynthesis, annotated with (1->3)-beta-D-glucan biosynthetic process (GO:0006075). GO:0006075 is a biological process from the Gene Ontology.
1,3-beta-D-Glucan Synthase Activity GO:0003843 Gene Ontology (GO) Relation: this pathophysiological event involves this molecular function This pathophysiological event involves 1,3-beta-D-Glucan Synthase Activity (GO:0003843). GO:0003843 is a molecular function from the Gene Ontology.
Downstream
Candida Cell-Wall Integrity and Viability Beta-1,3-glucan is an essential structural component of the Candida cell wall and supports fungal viability.
Show evidence (1 reference)
PMID:26190298 SUPPORT Other
"They are the first cell wall-active agents and target the fungal-specific enzyme glucan synthase, which catalyzes the biosynthesis of β-1,3-glucan, a key cell wall polymer."
Establishes the fungal-specific glucan-synthase activity and its beta-1,3-glucan product as the conserved echinocandin target. Evidence source is OTHER because this is a review.
Candida Cell-Wall Integrity and Viability
The beta-1,3-glucan-rich cell wall maintains Candida structural integrity and viability. This normal fungal function is upstream of the organism's ability to persist and invade; pharmacologic glucan depletion instead causes osmotic lysis.
Downstream
Candida Invasion of Normally Sterile Compartments A viable opportunistic Candida population can breach host barriers and establish infection in normally sterile sites, although this entry does not claim that cell-wall integrity alone is sufficient for invasion.
Candida Invasion of Normally Sterile Compartments
Under permissive host conditions, Candida crosses epithelial barriers or barriers associated with devices and establishes infection in blood or deep sterile tissues, distinguishing invasive disease from colonization or mucosal candidiasis.
Downstream
Candidemia and Hematogenous Dissemination Invasion into the bloodstream produces candidemia and enables hematogenous seeding of distant organs.
Candidemia and Hematogenous Dissemination
Candida bloodstream infection causes high-morbidity systemic disease and may seed ocular, hepatic, splenic, and other deep sites.
Downstream
Fungal sepsis
Hepatic candidiasis
Fungal splenic abscess
Candida chorioretinitis
Show evidence (1 reference)
PMID:36135696 SUPPORT Human Clinical
"Bloodstream infections caused by Candida yeasts (candidemia) are associated with high morbidity and mortality."
Directly identifies candidemia as a severe Candida bloodstream infection.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Invasive Candidiasis Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

5
Candidemia Clinical HP:0034749 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fungemia (HP:0034749). HP:0034749 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:36135696 SUPPORT Human Clinical
"Bloodstream infections caused by Candida yeasts (candidemia) are associated with high morbidity and mortality."
Binds Candida bloodstream infection to the HPO fungemia phenotype.
Fungal sepsis Clinical HP:5210141 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fungal sepsis (HP:5210141). HP:5210141 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:24157707 SUPPORT Other
"Candida species are by far the predominant agent of fungal sepsis"
Directly supports fungal sepsis as a severe invasive-Candida manifestation.
Hepatic candidiasis Clinical HP:5210167 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hepatic candidiasis (HP:5210167). HP:5210167 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:27709545 SUPPORT Human Clinical
"The diagnosis was established by demonstration of multiple abscesses in liver and spleen on ultrasound and computed tomography."
Human cases directly document hepatic abscess involvement.
Fungal splenic abscess Clinical HP:5210173 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fungal splenic abscess (HP:5210173). HP:5210173 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:27709545 SUPPORT Human Clinical
"The diagnosis was established by demonstration of multiple abscesses in liver and spleen on ultrasound and computed tomography."
Human cases directly document splenic abscess involvement.
Candida chorioretinitis OCCASIONAL Clinical HP:0012424 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Chorioretinitis (HP:0012424). HP:0012424 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:21765074 SUPPORT Human Clinical
"Of 370 patients, 49 had findings consistent with the diagnosis of ocular candidiasis at baseline, and an additional 11 patients developed abnormalities during treatment, totaling 60 patients with eye involvement (16%)."
The prospective candidemia cohort places ocular involvement in the OCCASIONAL band.
💊

Medical Actions

1
Anidulafungin Echinocandin Therapy
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: anidulafungin CHEBI:55346 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses anidulafungin (CHEBI:55346). CHEBI:55346 is a therapeutic agent from Chemical Entities of Biological Interest.
Intravenous anidulafungin is an echinocandin used as initial therapy for candidemia and other invasive Candida infections. It directly inhibits fungal beta-1,3-glucan synthase.
Mechanism Target:
INHIBITS Candida beta-1,3-Glucan Synthesis by Fks Glucan Synthase — Anidulafungin inhibits the Candida glucan-synthase complex, reducing production of the beta-1,3-glucan required for cell-wall integrity.
Show evidence (1 reference)
PMID:21694887 SUPPORT Other
"Anidulafungin and all echinocandins inhibit glucan synthase thus inhibiting the formation of 1,3-β-D-glucan which is an essential component of the fungal cell wall."
Directly supports anidulafungin inhibiting glucan synthase and thereby reducing the essential beta-1,3-glucan cell-wall polymer. Evidence source is OTHER because this is a review.
Show evidence (1 reference)
PMID:21694887 SUPPORT Other
"Because of its spectrum of activity, fungicidal nature, and tolerability it is an attractive first-line therapeutic choice for treating candidemia in both non-neutropenic and neutropenic patients."
Supports anidulafungin as a first-line option in candidemia. Evidence source is OTHER because this is a review.
🌍

Environmental Factors

3
Prolonged Marked Granulocytopenia
The cited threshold is more than 10 days with granulocytes below 0.5 × 10^9/L.
Show evidence (1 reference)
PMID:31159914 SUPPORT Other
"The clinical risk factors for invasive fungal infection include, among others, congenital immune deficiency, protracted (>10 days) marked granulocytopenia (<0.5 x 109/L), allogeneic stem-cell transplantation, and treatment with immunosuppressive drugs or corticosteroids."
Names prolonged marked granulocytopenia, at the duration and count threshold this entry records, among the clinical risk factors for invasive fungal infection.
Mechanism Target:
PREDISPOSES Candida Invasion of Normally Sterile Compartments
Show evidence (1 reference)
PMID:31159914 SUPPORT Other
"The clinical risk factors for invasive fungal infection include, among others, congenital immune deficiency, protracted (>10 days) marked granulocytopenia (<0.5 x 109/L), allogeneic stem-cell transplantation, and treatment with immunosuppressive drugs or corticosteroids."
The review explicitly lists prolonged marked granulocytopenia as a clinical risk factor.
Allogeneic Stem-Cell Transplantation
haematopoietic stem-cell transplantation ECTO:2000056 Environmental Conditions, Treatments and Exposures Ontology (ECTO) Relation: this environmental factor is this exposure This environmental factor is haematopoietic stem-cell transplantation, annotated with exposure to transplant surgery (ECTO:2000056). ECTO:2000056 is an exposure from the Environmental Conditions, Treatments and Exposures Ontology.
Show evidence (1 reference)
PMID:31159914 SUPPORT Other
"The clinical risk factors for invasive fungal infection include, among others, congenital immune deficiency, protracted (>10 days) marked granulocytopenia (<0.5 x 109/L), allogeneic stem-cell transplantation, and treatment with immunosuppressive drugs or corticosteroids."
Names allogeneic stem-cell transplantation among the clinical risk factors for invasive fungal infection, which is the association this exposure entry asserts.
Mechanism Target:
PREDISPOSES Candida Invasion of Normally Sterile Compartments
Show evidence (1 reference)
PMID:31159914 SUPPORT Other
"The clinical risk factors for invasive fungal infection include, among others, congenital immune deficiency, protracted (>10 days) marked granulocytopenia (<0.5 x 109/L), allogeneic stem-cell transplantation, and treatment with immunosuppressive drugs or corticosteroids."
The review explicitly lists allogeneic stem-cell transplantation as a clinical risk factor.
Immunosuppressive Drugs or Corticosteroids
exposure to immunosuppressive agent ECTO:9001747 Environmental Conditions, Treatments and Exposures Ontology (ECTO) Relation: this environmental factor is this exposure This environmental factor is exposure to immunosuppressive agent (ECTO:9001747). ECTO:9001747 is an exposure from the Environmental Conditions, Treatments and Exposures Ontology.
Show evidence (1 reference)
PMID:31159914 SUPPORT Other
"The clinical risk factors for invasive fungal infection include, among others, congenital immune deficiency, protracted (>10 days) marked granulocytopenia (<0.5 x 109/L), allogeneic stem-cell transplantation, and treatment with immunosuppressive drugs or corticosteroids."
Names treatment with immunosuppressive drugs or corticosteroids among the clinical risk factors for invasive fungal infection, which is the association this exposure entry asserts.
Mechanism Target:
PREDISPOSES Candida Invasion of Normally Sterile Compartments
Show evidence (1 reference)
PMID:31159914 SUPPORT Other
"The clinical risk factors for invasive fungal infection include, among others, congenital immune deficiency, protracted (>10 days) marked granulocytopenia (<0.5 x 109/L), allogeneic stem-cell transplantation, and treatment with immunosuppressive drugs or corticosteroids."
The review explicitly lists immunosuppressive drugs and corticosteroids as clinical risk factors.
🔬

Diagnosis

2
Candida Blood Culture
Isolation of Candida from blood culture remains the diagnostic gold standard for candidemia, but sensitivity is limited and turnaround can be slow.
Show evidence (1 reference)
PMID:36135696 SUPPORT Human Clinical
"Diagnosis remains challenging, with the current gold standard—isolation from blood culture (BC)—being limited by low sensitivity and long turnaround time."
Directly defines blood culture as the current standard while documenting its limitations.
Serum Beta-1,3-D-Glucan Assay
Serum beta-1,3-D-glucan is a nonculture adjunct that can support earlier candidemia diagnosis but does not identify the Candida species and must be interpreted with clinical context.
Show evidence (1 reference)
PMID:36135696 SUPPORT Human Clinical
"In conclusion, BDG testing demonstrated several advantages over PCR testing for the diagnosis of candidemia, including higher sensitivity and earlier diagnosis. However, BC remains essential, as BDG does not allow for species differentiation."
Supports BDG as an adjunct and records the species-identification limitation.
📊

Prevalence

1
General population; all invasive fungal infections, not Candida-specific
Annual Incidence 6 per 100,000 1–9 per 100,000
This is a deliberately broader all-invasive-fungal-infection incidence estimate and must not be interpreted as an invasive-candidiasis-specific rate. It is retained only as an order-of-magnitude epidemiologic context.
Show evidence (1 reference)
PMID:31159914 SUPPORT Other
"The incidence of invasive fungal infection is approximately 6 cases per 100 000 persons per year."
The review provides annual incidence for the broader invasive-fungal-infection category.
🦠

Infectious Agent

1
Candida species
Multiple species in the genus Candida cause invasive candidiasis, so the infectious-agent anchor is intentionally genus-level.
Candida NCBITaxon:5475 NCBI Taxonomy (NCBITaxon)
Show evidence (1 reference)
PMID:31159914 SUPPORT Other
"guidelines on the diagnosis and treatment of invasive fungal infections caused by Candida spp., Aspergillus spp., Mucorales, and Fusarium spp."
The review explicitly identifies Candida species as causes of invasive fungal infection. Evidence source is OTHER because this is a review.
{ }

Source YAML

click to show 
name: Invasive Candidiasis
creation_date: "2026-08-08T00:00:00Z"
category: Infectious Disease
synonyms:
- Invasive candidosis
- Systemic candidiasis
description: >-
  Invasive candidiasis is infection by Candida species in a normally sterile
  body compartment. Candidemia, in which Candida is recovered from the
  bloodstream, is its most common named form. The entry focuses narrowly on the
  conserved fungal-cell-wall target that explains why echinocandins are used:
  Fks glucan synthase, encoded principally by FKS1 with FKS2 additionally
  relevant in species such as Candida glabrata, produces beta-1,3-glucan, and
  anidulafungin inhibits that enzyme to compromise the Candida cell wall.
disease_term:
  preferred_term: invasive candidiasis
  term:
    id: MONDO:0044067
    label: candidiasis, invasive
parents:
- Candidiasis
- Invasive fungal infection
classifications:
  harrisons_chapter:
  - classification_value: INFECTIOUS_DISEASES
    evidence:
    - reference: PMID:36135696
      reference_title: "Performance of Multiplex PCR and β-1,3-D-Glucan Testing for the Diagnosis of Candidemia."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Bloodstream infections caused by Candida yeasts (candidemia) are associated with high morbidity and mortality.
      explanation: Invasive candidiasis is a Candida infectious disease, placing it in Harrison's Infectious Diseases Part.
prevalence:
- population: General population; all invasive fungal infections, not Candida-specific
  measure_type: ANNUAL_INCIDENCE
  prevalence_class: BAND_1_9_PER_100000
  rate_per_100000: 6
  notes: >-
    This is a deliberately broader all-invasive-fungal-infection incidence
    estimate and must not be interpreted as an invasive-candidiasis-specific
    rate. It is retained only as an order-of-magnitude epidemiologic context.
  evidence:
  - reference: PMID:31159914
    reference_title: Invasive Fungal Infection.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: The incidence of invasive fungal infection is approximately 6 cases per 100 000 persons per year.
    explanation: The review provides annual incidence for the broader invasive-fungal-infection category.
has_subtypes:
- name: Candidemia
  subtype_term:
    preferred_term: candidemia
    term:
      id: MONDO:0044070
      label: candidemia
  description: >-
    Bloodstream infection with Candida species; candidemia is a form of
    invasive candidiasis and the principal clinical setting represented by the
    echinocandin evidence in this entry.
  evidence:
  - reference: PMID:36135696
    reference_title: "Performance of Multiplex PCR and β-1,3-D-Glucan Testing for the Diagnosis of Candidemia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Bloodstream infections caused by Candida yeasts (candidemia) are associated with high morbidity and mortality.
    explanation: Defines candidemia as Candida bloodstream infection and supports it as an invasive-candidiasis subtype.
infectious_agent:
- name: Candida species
  infectious_agent_term:
    preferred_term: Candida
    term:
      id: NCBITaxon:5475
      label: Candida
  description: >-
    Multiple species in the genus Candida cause invasive candidiasis, so the
    infectious-agent anchor is intentionally genus-level.
  evidence:
  - reference: PMID:31159914
    reference_title: Invasive Fungal Infection.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      guidelines on the diagnosis and treatment of invasive fungal infections
      caused by Candida spp., Aspergillus spp., Mucorales, and Fusarium spp.
    explanation: >-
      The review explicitly identifies Candida species as causes of invasive
      fungal infection. Evidence source is OTHER because this is a review.
environmental:
- name: Prolonged Marked Granulocytopenia
  effect: Predisposition to invasive fungal infection
  notes: The cited threshold is more than 10 days with granulocytes below 0.5 × 10^9/L.
  influences_mechanisms:
  - target: Candida Invasion of Normally Sterile Compartments
    environmental_effect: PREDISPOSES
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:31159914
      reference_title: Invasive Fungal Infection.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        The clinical risk factors for invasive fungal infection include, among
        others, congenital immune deficiency, protracted (>10 days) marked
        granulocytopenia (<0.5 x 109/L), allogeneic stem-cell transplantation,
        and treatment with immunosuppressive drugs or corticosteroids.
      explanation: The review explicitly lists prolonged marked granulocytopenia as a clinical risk factor.
  evidence:
  - reference: PMID:31159914
    reference_title: Invasive Fungal Infection.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The clinical risk factors for invasive fungal infection include, among
      others, congenital immune deficiency, protracted (>10 days) marked
      granulocytopenia (<0.5 x 109/L), allogeneic stem-cell transplantation,
      and treatment with immunosuppressive drugs or corticosteroids.
    explanation: >
      Names prolonged marked granulocytopenia, at the duration and count threshold this entry
      records, among the clinical risk factors for invasive fungal infection.
- name: Allogeneic Stem-Cell Transplantation
  exposure_term:
    preferred_term: haematopoietic stem-cell transplantation
    term:
      id: ECTO:2000056
      label: exposure to transplant surgery
  effect: Predisposition to invasive fungal infection
  influences_mechanisms:
  - target: Candida Invasion of Normally Sterile Compartments
    environmental_effect: PREDISPOSES
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:31159914
      reference_title: Invasive Fungal Infection.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        The clinical risk factors for invasive fungal infection include, among
        others, congenital immune deficiency, protracted (>10 days) marked
        granulocytopenia (<0.5 x 109/L), allogeneic stem-cell transplantation,
        and treatment with immunosuppressive drugs or corticosteroids.
      explanation: The review explicitly lists allogeneic stem-cell transplantation as a clinical risk factor.
  evidence:
  - reference: PMID:31159914
    reference_title: Invasive Fungal Infection.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The clinical risk factors for invasive fungal infection include, among
      others, congenital immune deficiency, protracted (>10 days) marked
      granulocytopenia (<0.5 x 109/L), allogeneic stem-cell transplantation,
      and treatment with immunosuppressive drugs or corticosteroids.
    explanation: >
      Names allogeneic stem-cell transplantation among the clinical risk factors for invasive
      fungal infection, which is the association this exposure entry asserts.
- name: Immunosuppressive Drugs or Corticosteroids
  exposure_term:
    preferred_term: exposure to immunosuppressive agent
    term:
      id: ECTO:9001747
      label: exposure to immunosuppressive agent
  effect: Predisposition to invasive fungal infection
  influences_mechanisms:
  - target: Candida Invasion of Normally Sterile Compartments
    environmental_effect: PREDISPOSES
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:31159914
      reference_title: Invasive Fungal Infection.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        The clinical risk factors for invasive fungal infection include, among
        others, congenital immune deficiency, protracted (>10 days) marked
        granulocytopenia (<0.5 x 109/L), allogeneic stem-cell transplantation,
        and treatment with immunosuppressive drugs or corticosteroids.
      explanation: The review explicitly lists immunosuppressive drugs and corticosteroids as clinical risk factors.
  evidence:
  - reference: PMID:31159914
    reference_title: Invasive Fungal Infection.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The clinical risk factors for invasive fungal infection include, among
      others, congenital immune deficiency, protracted (>10 days) marked
      granulocytopenia (<0.5 x 109/L), allogeneic stem-cell transplantation,
      and treatment with immunosuppressive drugs or corticosteroids.
    explanation: >
      Names treatment with immunosuppressive drugs or corticosteroids among the clinical risk
      factors for invasive fungal infection, which is the association this exposure entry
      asserts.
pathophysiology:
- name: Candida beta-1,3-Glucan Synthesis by Fks Glucan Synthase
  description: >-
    The Candida plasma-membrane glucan-synthase complex uses the catalytic
    subunit encoded principally by FKS1; FKS2 supplies additional catalytic
    capacity in species such as Candida glabrata. The complex synthesizes
    beta-1,3-glucan, an essential structural polymer of the fungal cell wall.
    This fungus-specific activity
    is the direct therapeutic vulnerability inhibited by echinocandins. The
    node is intentionally target-only: it does not assert that normal wall
    synthesis positively causes the intervention-conditional wall failure that
    follows pharmacologic inhibition.
  biological_scale: MOLECULAR
  role: therapeutic_vulnerability
  conforms_to: >-
    fungal_cell_wall_glucan_synthesis_inhibition#beta-1,3-Glucan Synthesis at
    the Plasma Membrane by Fks Glucan Synthase
  biological_processes:
  - preferred_term: beta-1,3-Glucan Biosynthesis
    term:
      id: GO:0006075
      label: (1->3)-beta-D-glucan biosynthetic process
  molecular_functions:
  - preferred_term: 1,3-beta-D-Glucan Synthase Activity
    term:
      id: GO:0003843
      label: 1,3-beta-D-glucan synthase activity
  evidence:
  - reference: PMID:26190298
    reference_title: Mechanisms of echinocandin antifungal drug resistance.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      They are the first cell wall-active agents and target the fungal-specific
      enzyme glucan synthase, which catalyzes the biosynthesis of β-1,3-glucan,
      a key cell wall polymer.
    explanation: >-
      Establishes the fungal-specific glucan-synthase activity and its
      beta-1,3-glucan product as the conserved echinocandin target. Evidence
      source is OTHER because this is a review.
  downstream:
  - target: Candida Cell-Wall Integrity and Viability
    causal_link_type: DIRECT
    description: Beta-1,3-glucan is an essential structural component of the Candida cell wall and supports fungal viability.
    evidence:
    - reference: PMID:21694887
      reference_title: Anidulafungin and its role in candida infections.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Anidulafungin and all echinocandins inhibit glucan synthase thus
        inhibiting the formation of 1,3-β-D-glucan which is an essential
        component of the fungal cell wall.
      explanation: Establishes the direct structural link from glucan synthesis to cell-wall integrity.
- name: Candida Cell-Wall Integrity and Viability
  biological_scale: CELLULAR
  role: effector
  description: >-
    The beta-1,3-glucan-rich cell wall maintains Candida structural integrity
    and viability. This normal fungal function is upstream of the organism's
    ability to persist and invade; pharmacologic glucan depletion instead causes
    osmotic lysis.
  downstream:
  - target: Candida Invasion of Normally Sterile Compartments
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      A viable opportunistic Candida population can breach host barriers and
      establish infection in normally sterile sites, although this entry does
      not claim that cell-wall integrity alone is sufficient for invasion.
    evidence:
    - reference: PMID:36135696
      reference_title: "Performance of Multiplex PCR and β-1,3-D-Glucan Testing for the Diagnosis of Candidemia."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        However, as an opportunistic pathogen, this fungus can also cause a
        variety of infections ranging from superficial and local infections,
        such as thrush or vulvovaginitis, to invasive systemic infections,
        including Candida bloodstream infection (BSI).
      explanation: Supports opportunistic progression to systemic invasion but not a single sufficient molecular cause.
- name: Candida Invasion of Normally Sterile Compartments
  biological_scale: ORGANISM
  role: trigger
  description: >-
    Under permissive host conditions, Candida crosses epithelial barriers or
    barriers associated with devices and establishes infection in blood or deep
    sterile tissues, distinguishing invasive disease from colonization or mucosal
    candidiasis.
  downstream:
  - target: Candidemia and Hematogenous Dissemination
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: Invasion into the bloodstream produces candidemia and enables hematogenous seeding of distant organs.
    evidence:
    - reference: PMID:22431804
      reference_title: "Performance of Candida real-time polymerase chain reaction, β-D-glucan assay, and blood cultures in the diagnosis of invasive candidiasis."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Patients with IC had candidemia (n = 17), deep-seated candidiasis (n = 33), or both (n = 5).
      explanation: A prospective clinical cohort directly documents bloodstream and deep-seated invasive presentations.
- name: Candidemia and Hematogenous Dissemination
  biological_scale: ORGANISM
  role: consequence
  description: >-
    Candida bloodstream infection causes high-morbidity systemic disease and
    may seed ocular, hepatic, splenic, and other deep sites.
  evidence:
  - reference: PMID:36135696
    reference_title: "Performance of Multiplex PCR and β-1,3-D-Glucan Testing for the Diagnosis of Candidemia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Bloodstream infections caused by Candida yeasts (candidemia) are associated with high morbidity and mortality.
    explanation: Directly identifies candidemia as a severe Candida bloodstream infection.
  downstream:
  - target: Fungal sepsis
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:24157707
      reference_title: Invasive candidiasis as a cause of sepsis in the critically ill patient.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: Candida species are by far the predominant agent of fungal sepsis
      explanation: Supports Candida bloodstream invasion as a cause of fungal sepsis.
  - target: Hepatic candidiasis
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Hematogenous seeding of the liver
    evidence:
    - reference: PMID:27709545
      reference_title: Hepatosplenic candidasis, a fatal disease?
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: The diagnosis was established by demonstration of multiple abscesses in liver and spleen on ultrasound and computed tomography.
      explanation: Human cases document hepatic and splenic abscesses in disseminated candidiasis.
  - target: Fungal splenic abscess
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Hematogenous seeding of the spleen
    evidence:
    - reference: PMID:27709545
      reference_title: Hepatosplenic candidasis, a fatal disease?
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: The diagnosis was established by demonstration of multiple abscesses in liver and spleen on ultrasound and computed tomography.
      explanation: Human cases document hepatic and splenic abscesses in disseminated candidiasis.
  - target: Candida chorioretinitis
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Hematogenous seeding of the choroid and retina
    evidence:
    - reference: PMID:21765074
      reference_title: Ocular manifestations of candidemia.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Of these patients, probable Candida eye infection was diagnosed in 40
        patients (6 with endophthalmitis, 34 with chorioretinitis), and possible
        Candida eye infection in 20 (all with chorioretinitis).
      explanation: Prospective candidemia data document chorioretinitis and endophthalmitis after bloodstream infection.
phenotypes:
- name: Candidemia
  category: Clinical
  phenotype_term:
    preferred_term: Fungemia
    term:
      id: HP:0034749
      label: Fungemia
  evidence:
  - reference: PMID:36135696
    reference_title: "Performance of Multiplex PCR and β-1,3-D-Glucan Testing for the Diagnosis of Candidemia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Bloodstream infections caused by Candida yeasts (candidemia) are associated with high morbidity and mortality.
    explanation: Binds Candida bloodstream infection to the HPO fungemia phenotype.
- name: Fungal sepsis
  category: Clinical
  phenotype_term:
    preferred_term: Fungal sepsis
    term:
      id: HP:5210141
      label: Fungal sepsis
  evidence:
  - reference: PMID:24157707
    reference_title: Invasive candidiasis as a cause of sepsis in the critically ill patient.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: Candida species are by far the predominant agent of fungal sepsis
    explanation: Directly supports fungal sepsis as a severe invasive-Candida manifestation.
- name: Hepatic candidiasis
  category: Clinical
  phenotype_term:
    preferred_term: Hepatic candidiasis
    term:
      id: HP:5210167
      label: Hepatic candidiasis
  evidence:
  - reference: PMID:27709545
    reference_title: Hepatosplenic candidasis, a fatal disease?
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: The diagnosis was established by demonstration of multiple abscesses in liver and spleen on ultrasound and computed tomography.
    explanation: Human cases directly document hepatic abscess involvement.
- name: Fungal splenic abscess
  category: Clinical
  phenotype_term:
    preferred_term: Fungal splenic abscess
    term:
      id: HP:5210173
      label: Fungal splenic abscess
  evidence:
  - reference: PMID:27709545
    reference_title: Hepatosplenic candidasis, a fatal disease?
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: The diagnosis was established by demonstration of multiple abscesses in liver and spleen on ultrasound and computed tomography.
    explanation: Human cases directly document splenic abscess involvement.
- name: Candida chorioretinitis
  category: Clinical
  frequency: OCCASIONAL
  phenotype_term:
    preferred_term: Chorioretinitis
    term:
      id: HP:0012424
      label: Chorioretinitis
  evidence:
  - reference: PMID:21765074
    reference_title: Ocular manifestations of candidemia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Of 370 patients, 49 had findings consistent with the diagnosis of ocular
      candidiasis at baseline, and an additional 11 patients developed
      abnormalities during treatment, totaling 60 patients with eye involvement
      (16%).
    explanation: The prospective candidemia cohort places ocular involvement in the OCCASIONAL band.
diagnosis:
- name: Candida Blood Culture
  description: >-
    Isolation of Candida from blood culture remains the diagnostic gold standard
    for candidemia, but sensitivity is limited and turnaround can be slow.
  evidence:
  - reference: PMID:36135696
    reference_title: "Performance of Multiplex PCR and β-1,3-D-Glucan Testing for the Diagnosis of Candidemia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Diagnosis remains challenging, with the current gold standard—isolation
      from blood culture (BC)—being limited by low sensitivity and long
      turnaround time.
    explanation: Directly defines blood culture as the current standard while documenting its limitations.
- name: Serum Beta-1,3-D-Glucan Assay
  description: >-
    Serum beta-1,3-D-glucan is a nonculture adjunct that can support earlier
    candidemia diagnosis but does not identify the Candida species and must be
    interpreted with clinical context.
  evidence:
  - reference: PMID:36135696
    reference_title: "Performance of Multiplex PCR and β-1,3-D-Glucan Testing for the Diagnosis of Candidemia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In conclusion, BDG testing demonstrated several advantages over PCR
      testing for the diagnosis of candidemia, including higher sensitivity and
      earlier diagnosis. However, BC remains essential, as BDG does not allow
      for species differentiation.
    explanation: Supports BDG as an adjunct and records the species-identification limitation.
treatments:
- name: Anidulafungin Echinocandin Therapy
  description: >-
    Intravenous anidulafungin is an echinocandin used as initial therapy for
    candidemia and other invasive Candida infections. It directly inhibits
    fungal beta-1,3-glucan synthase.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: anidulafungin
      term:
        id: CHEBI:55346
        label: anidulafungin
  therapeutic_modality: PEPTIDE
  target_mechanisms:
  - target: Candida beta-1,3-Glucan Synthesis by Fks Glucan Synthase
    treatment_effect: INHIBITS
    description: >-
      Anidulafungin inhibits the Candida glucan-synthase complex, reducing
      production of the beta-1,3-glucan required for cell-wall integrity.
    evidence:
    - reference: PMID:21694887
      reference_title: Anidulafungin and its role in candida infections.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Anidulafungin and all echinocandins inhibit glucan synthase thus
        inhibiting the formation of 1,3-β-D-glucan which is an essential
        component of the fungal cell wall.
      explanation: >-
        Directly supports anidulafungin inhibiting glucan synthase and thereby
        reducing the essential beta-1,3-glucan cell-wall polymer. Evidence
        source is OTHER because this is a review.
  evidence:
  - reference: PMID:21694887
    reference_title: Anidulafungin and its role in candida infections.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Because of its spectrum of activity, fungicidal nature, and tolerability
      it is an attractive first-line therapeutic choice for treating candidemia
      in both non-neutropenic and neutropenic patients.
    explanation: >-
      Supports anidulafungin as a first-line option in candidemia. Evidence
      source is OTHER because this is a review.
review_notes: >-
  This conformance tranche uses the reviewer-directed minimum-content route
  because no Invasive Candidiasis deep-research artifact was available. Clinical
  manifestations, diagnosis, epidemiologic context, risk factors, and a connected
  invasion-to-dissemination pathograph were therefore added from primary studies
  and the already-cached clinical review. Anidulafungin remains the representative
  treatment with direct target and first-line candidemia evidence; caspofungin,
  micafungin, and rezafungin are named in the shared class module but require
  their own disease-specific evidence before separate treatment records are added.