Bloodstream and deep-tissue infection by Candida species; common nosocomial fungal infection with high mortality.
Also known as: candidemia, invasive candidiasis, Candida bloodstream infection, Candida albicans, Candida auris
Overview
Spectrum of bloodstream and deep-organ infections caused by Candida species. Encompasses candidemia (Candida in blood), deep-seated candidiasis (intra-abdominal, hepatosplenic, ocular, cardiac), and acute disseminated candidiasis. Distinct from superficial mucocutaneous candidiasis (thrush, vulvovaginitis).
Epidemiology
Among the leading causes of healthcare-associated bloodstream infection, especially in ICU patients. C. albicans remains most common but non-albicans species (C. glabrata, C. parapsilosis, C. krusei, C. tropicalis, C. auris) are increasingly prevalent. C. auris is multidrug-resistant and associated with healthcare outbreaks. Mortality 30-50% in candidemia.
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Question 1Infectious DiseaseMedium
A 58-year-old man in the medical ICU on day 10 of broad-spectrum antibiotics for perforated diverticulitis develops new fever to 39.2 C and hypotension. He has a triple-lumen central venous catheter and has been receiving total parenteral nutrition. BP 88/52 mm Hg, HR 118 bpm. Exam shows no new focal source. Two sets of blood cultures drawn from peripheral sites both grow budding yeast within 48 hours. Which of the following is the most likely diagnosis?
ACandidemia
BTrichosporonosis
CCryptococcemia
DHistoplasmosis
EAspergillosis
Reveal answer & full explanation
Correct answer: A — Candidemia
ACandidemia✓
BTrichosporonosis
CCryptococcemia
DHistoplasmosis
EAspergillosis
Why Candidemia is correct
Candidemia is bloodstream infection with Candida species and is the most common invasive fungal infection in hospitalized patients
Major risk factors include prolonged broad-spectrum antibiotics, central venous catheters, total parenteral nutrition, ICU stay, and abdominal surgery — all present in this case
Blood cultures growing budding yeast in this setting are essentially diagnostic of candidemia pending species identification; C. albicans and C. glabrata predominate
Why the others are wrong
Cryptococcemia — buzzword-matching on "yeast" without integrating the risk profile; cryptococcosis arises in advanced HIV or other profound T-cell deficiency and presents with meningoencephalitis, and the organism is an encapsulated yeast on India ink rather than the simple budding yeast cultured here
Histoplasmosis — confused-with-X endemic mycosis; this dimorphic fungus of the Ohio and Mississippi River valleys causes pulmonary or disseminated disease and does not appear as routine blood-culture budding yeast in an ICU patient with catheter and TPN risk factors
Aspergillosis — buzzword-matching on "fungus," but Aspergillus is a mold, not a yeast, rarely grows from blood cultures even in disseminated disease, and appears as septate hyphae in tissue
Trichosporonosis — line-associated yeast-like infection that tempts in a catheter-dependent ICU patient on prolonged broad-spectrum antibiotics, but invasive Trichosporon disease occurs mainly with neutropenia from hematologic malignancy, its cultures show arthroconidia and hyphae as well as budding cells, and it is far rarer than Candida, which remains the expected cause of budding yeast in two blood culture sets with these risk factors
Question 2Infectious DiseaseMedium
A 64-year-old man in the surgical ICU on day 12 after exploratory laparotomy for a perforated diverticulum has new fevers to 39.2°C and rising vasopressor requirements. He has a central venous catheter and has received broad-spectrum antibiotics, including meropenem and vancomycin, for the past 9 days. He is also receiving total parenteral nutrition. Blood cultures drawn from a peripheral vein and the central line are pending, and serum (1,3)-beta-D-glucan is markedly elevated. A funduscopic exam shows scattered yellow-white chorioretinal lesions. Which of the following is the most likely diagnosis?
AInvasive pulmonary aspergillosis
BInvasive candidiasis (candidemia)
CChronic hepatosplenic candidiasis
DDisseminated cryptococcal disease
ECentral line Candida colonization
Reveal answer & full explanation
Correct answer: B — Invasive candidiasis (candidemia)
AInvasive pulmonary aspergillosis
BInvasive candidiasis (candidemia)✓
CChronic hepatosplenic candidiasis
DDisseminated cryptococcal disease
ECentral line Candida colonization
Why Invasive candidiasis (candidemia) is correct
This is the classic candidemia host: prolonged ICU stay, recent abdominal surgery with GI perforation, a central venous catheter, total parenteral nutrition, and persistent broad-spectrum antibiotic exposure that selects for Candida.
A markedly elevated serum (1,3)-beta-D-glucan supports invasive fungal infection, and with these risk factors Candida is the expected pathogen; blood cultures confirm candidemia but miss roughly half of invasive candidiasis, so empiric antifungal therapy (an echinocandin per IDSA) should not wait for them.
The yellow-white chorioretinal lesions are chorioretinitis from hematogenous seeding, a hallmark of disseminated candidiasis. IDSA recommends an ophthalmology exam in every patient with candidemia within the first week.
Why the others are wrong
Chronic hepatosplenic candidiasis - also called chronic disseminated candidiasis, it presents with persistent fever and RUQ pain plus target liver/spleen lesions after neutrophil recovery in hematologic malignancy, not as acute septic shock with chorioretinitis in a post-surgical ICU patient.
Central line Candida colonization - colonization of the catheter does not explain septic shock or chorioretinitis; retinal lesions mean Candida has seeded the bloodstream and the eye, which is invasive disease, and IDSA treats any Candida grown from blood as a true pathogen, never a contaminant.
Disseminated cryptococcal disease - Cryptococcus disseminates mainly in advanced HIV, organ transplant, or high-dose corticosteroid recipients and usually presents as meningoencephalitis; it has no link to TPN, abdominal surgery, or broad-spectrum antibiotics, and the beta-D-glucan assay detects Cryptococcus poorly.
Invasive pulmonary aspergillosis - the markedly elevated (1,3)-beta-D-glucan is tempting because the assay also detects Aspergillus, but invasive aspergillosis occurs mainly with prolonged neutropenia, hematologic malignancy, transplantation, or high-dose corticosteroids and causes pulmonary nodules, infiltrates, or cavitation, none of which are described; a central line, TPN, abdominal surgery, and chorioretinitis point to Candida.
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Central venous catheter, total parenteral nutrition
Broad-spectrum antibiotic exposure
Prolonged ICU stay, mechanical ventilation
Recent abdominal or cardiac surgery, GI perforation, anastomotic leak
Hemodialysis
Hematologic malignancy with neutropenia, HSCT
Solid organ transplantation
Diabetes mellitus, total parenteral nutrition, prolonged hyperalimentation
Injection drug use (especially endocarditis and ocular disease)
Preterm neonates with low birth weight
Pathophysiology
Candida species are commensals of the GI tract and skin. Translocation across damaged mucosal barriers (e.g., chemotherapy-induced mucositis, surgical anastomosis) or seeding from central venous catheters allows bloodstream entry. Candida adheres to vascular and prosthetic surfaces and forms biofilms, complicating eradication. Hematogenous dissemination targets the retina, heart valves, kidneys, liver, spleen, brain, and bones.
Clinical presentation
Symptoms
Persistent fever and chills despite broad-spectrum antibiotics
Sepsis or septic shock without obvious bacterial source
Skin: macronodular erythematous skin lesions in neutropenic patients (disseminated candidiasis)
Visual changes from chorioretinitis or endophthalmitis
Heart failure or new murmur in Candida endocarditis
RUQ pain and elevated alkaline phosphatase in hepatosplenic candidiasis (after marrow recovery)
Signs / physical exam
Fever, often refractory to antibiotics
Erythematous macronodular skin lesions in neutropenia
Funduscopic findings: yellow-white chorioretinal lesions with vitreous haze in endophthalmitis
New cardiac murmur, peripheral emboli in endocarditis
Hepatosplenomegaly in chronic disseminated form
Classic findings
Persistent fever in an ICU patient with a central line, broad-spectrum antibiotics, and blood cultures growing yeast. Ophthalmologic exam revealing chorioretinitis. Pseudohyphae and yeast on Gram stain.
Differential diagnosis
Bacterial bloodstream infection / sepsis — Gram stain and culture distinguish; coverage often empirical pending data
Catheter-related bloodstream infection (CRBSI) — Differential time to positivity, paired peripheral/central cultures
Endocarditis (bacterial) — Persistent bacteremia, valvular vegetations on echo; combine fungal and bacterial workup
Hepatosplenic candidiasis (chronic disseminated) — Persistent fever after neutrophil recovery in hematologic malignancy, target lesions in liver/spleen on imaging
Aspergillosis or mucormycosis — Different histology, imaging; biopsy where feasible
Diagnostic workup
Diagnostic criteria
Definitive diagnosis: isolation of Candida from blood or normally sterile site. Deep-seated candidiasis without candidemia is supported by histopathology with culture from sterile tissue.
Labs
Blood cultures from peripheral vein and from each lumen of central catheter (sensitivity ~50-70% per single set)
Beta-D-glucan — sensitive for invasive candidiasis (negative does not rule out, false positives common)
T2Candida assay (rapid PCR-based) when available
Speciation and antifungal susceptibility — critical for C. glabrata (azole resistance), C. krusei (intrinsic fluconazole resistance), C. auris (multidrug resistance)
CBC, BMP, LFTs
Ophthalmologic examination by ophthalmology — dilated exam within the first week of diagnosis in non-neutropenic patients; in neutropenic patients, within the first week after neutrophil recovery (retinal lesions are minimal until neutrophils return)
Imaging
TTE and TEE if endocarditis suspected (persistent candidemia, prosthetic valves, IV drug use)
Abdominal CT or MRI for hepatosplenic candidiasis (target/bullseye lesions)
MRI brain for CNS candidiasis
Spine imaging if back pain (vertebral osteomyelitis)
Treatment
First-line
Echinocandin — caspofungin 70 mg IV loading then 50 mg daily, micafungin 100 mg IV daily, or anidulafungin 200 mg IV loading then 100 mg daily — preferred initial therapy for candidemia in most adults
Step-down to fluconazole 400-800 mg PO daily after clinical improvement and demonstration of susceptibility (typically after 5-7 days, except in C. glabrata or C. krusei)
Liposomal amphotericin B 3-5 mg/kg/day as alternative for intolerance, limited availability, or resistance to other agents; preferred (with or without flucytosine) for CNS candidiasis
Remove or replace central venous catheters whenever feasible (improves outcomes)
Treat candidemia for at least 14 days after first negative blood culture and resolution of signs/symptoms
Ophthalmology consult in every patient with candidemia
Daily blood cultures until clearance documented
Second-line / adjunct
Voriconazole as alternative azole, particularly for C. krusei
C. auris: echinocandin first-line, but susceptibility-guided due to resistance; isolate patients to prevent nosocomial spread
Endocarditis: liposomal amphotericin B +/- flucytosine; valve replacement usually required; prolonged suppression with fluconazole
Endophthalmitis: systemic therapy with good ocular penetration (fluconazole or voriconazole) +/- intravitreal antifungal; vitrectomy for vitritis
Hepatosplenic (chronic disseminated) candidiasis: lipid amphotericin B or an echinocandin for several weeks, then oral fluconazole until lesions resolve on imaging (usually months); short-course NSAIDs or corticosteroids only for persistent debilitating fever
Complications
Endocarditis with valvular destruction and embolization
Endophthalmitis with permanent vision loss
Septic shock and multiorgan failure
Suppurative thrombophlebitis
Renal candidiasis, pyelonephritis with fungal balls
Vertebral osteomyelitis and discitis
Emergence of azole-resistant or multidrug-resistant species (C. glabrata, C. auris)
PANCE pearls
Echinocandins are the preferred initial therapy for candidemia in most adults — broad coverage and excellent safety profile.
Every patient with candidemia needs a dilated eye exam within the first week (in neutropenic patients, within the first week after neutrophil recovery) — endophthalmitis is often asymptomatic early.
The central venous catheter is the most important modifiable risk factor (biofilm seeds the bloodstream); remove it in candidemia whenever clinically feasible.
C. krusei is intrinsically fluconazole-resistant; C. glabrata is often dose-dependent or resistant — speciation and susceptibility matter.
C. auris is multidrug-resistant and a public health threat — institute contact precautions, alert infection control, and use echinocandins with susceptibility-guided adjustment.
References
IDSA 2016 — Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America (Pappas et al., Clin Infect Dis 2016)
CDC — CDC — Candida auris and invasive candidiasis: clinical and infection control guidance
ECMM/ISHAM/ASM 2025 — Global guideline for the diagnosis and management of candidiasis: an initiative of the ECMM in cooperation with ISHAM and ASM (Cornely et al., Lancet Infect Dis 2025;25:e280-e293)
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