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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Risk factors
- 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
- Septic thrombophlebitis — Persistent fungemia despite catheter removal, identify suppurative thrombus on imaging
- 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 — recommended in all candidemia within 1 week of diagnosis (4-7 days in neutropenic hosts as eye findings can be delayed)
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, particularly in neonates and in CNS or eye disease
- 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 candidiasis: prolonged azole therapy with steroids to dampen inflammatory response in chronic disseminated form
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 an ophthalmology consult within a week — endophthalmitis is often asymptomatic early.
- Remove central venous catheters 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
- ESCMID — ESCMID guideline for the diagnosis and management of Candida diseases
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