Overview
Invasive Candidiasis
1. Clinical Overview
Summary
Invasive Candidiasis refers to Candida infection in the bloodstream (Candidemia) or deep-seated organ infection. It is a serious, often nosocomial (hospital-acquired) fungal infection with a mortality of 30-50% in critically ill patients. Risk factors include broad-spectrum antibiotics, central venous catheters, Total Parenteral Nutrition (TPN), abdominal surgery, neutropenia, and ICU admission. Candida albicans remains the most common species, but non-albicans species (C. glabrata, C. parapsilosis, C. auris) are increasingly prevalent and may be azole-resistant. Management involves Echinocandins as first-line therapy, source control (line removal), and mandatory ophthalmology review (Candida endophthalmitis). [1,2]
Clinical Pearls
Remove the Line: Central venous catheters are the most common source. Remove or exchange all CVCs in all patients with candidemia whenever feasible.
Eye Exam is Mandatory: All patients with candidemia need dilated fundoscopy (Ophthalmology) within 1 week. Candida endophthalmitis causes blindness if untreated.
Persistent Fever on Antibiotics: In an ICU patient with fever not responding to antibiotics, think fungal sepsis. Start empirical antifungal therapy.
C. auris is Different: Multi-drug resistant, transmissible, survives on surfaces. Requires strict infection control measures.
2. Epidemiology
Incidence
- Hospital Incidence: 0.5-1.5 cases per 1,000 hospital admissions.
- ICU: Up to 10x higher incidence in intensive care.
- Mortality: 30-50% (attributable mortality ~20-25%).
Species Distribution
| Species | Prevalence | Notes |
|---|---|---|
| Candida albicans | 40-60% | Most common. Usually Fluconazole-sensitive. |
| Candida glabrata | 15-25% | Increasingly common. Often Fluconazole-resistant. Echinocandin of choice. |
| Candida parapsilosis | 10-20% | Associated with CVCs, TPN, neonates. May have reduced Echinocandin susceptibility (use Fluconazole if sensitive). |
| Candida tropicalis | 5-15% | Common in neutropenic patients. Usually azole-sensitive. |
| Candida krusei | less than 5% | Intrinsically Fluconazole-resistant. Echinocandin or Amphotericin B. |
| Candida auris | Emerging | Multi-drug resistant (azoles, polyenes, echinocandins). Hospital outbreaks. High mortality. Infection control priority. |
Risk Factors
| Factor | Mechanism |
|---|---|
| Central Venous Catheter (CVC) | Biofilm formation on catheter. Most important source. |
| Broad-Spectrum Antibiotics | Disrupt normal flora → Candida overgrowth. |
| Total Parenteral Nutrition (TPN) | High glucose → Candida growth. Line colonisation. |
| Abdominal Surgery | Especially GI perforation, anastomotic leak. Candida in peritoneal cavity. |
| Neutropenia | Impaired neutrophil killing. Hematological malignancy patients. |
| Corticosteroids / Immunosuppression | Impaired cell-mediated immunity. |
| Diabetes Mellitus | Hyperglycemia impairs immune function. |
| Renal Replacement Therapy | Dialysis catheters. ICU population. |
| Severe Burns | Skin barrier breach. |
| Prolonged ICU Stay | Exposure to multiple risk factors. |
3. Pathophysiology
Mechanism of Invasive Candidiasis
- Colonisation: Candida normally colonises GI tract, skin, and mucosal surfaces (commensal).
- Barrier Breach: Risk factors (CVCs, surgery, GI leak) allow Candida entry into bloodstream or deep tissues.
- Bloodstream Invasion: Candidemia. Can seed multiple organs.
- Biofilm Formation: On CVCs. Protects Candida from antifungals and immune system. Makes line removal essential.
- Disseminated Candidiasis: Haematogenous spread to eyes (endophthalmitis), heart (endocarditis), kidneys, liver, spleen, brain.
- Inflammatory Response: Fungal cell wall components (beta-glucan, mannan) trigger host inflammation → sepsis, organ dysfunction.
Virulence Factors
- Adhesins: Allow binding to host tissues and catheters.
- Biofilm: Protects from antifungals and host immunity.
- Hyphal Transition: C. albicans switches from yeast to hyphae form to invade tissues.
- Secreted Enzymes: Aspartyl proteases, phospholipases → tissue damage.
4. Differential Diagnosis (Nosocomial Sepsis)
| Condition | Key Features |
|---|---|
| Invasive Candidiasis | Risk factors (CVC, TPN, antibiotics). Fever not responding to antibiotics. Blood cultures +ve for Candida. |
| Bacterial Sepsis (Gram-negative / Gram-positive) | More common. Blood cultures +ve bacteria. Responds to appropriate antibiotics. |
| Invasive Aspergillosis | Neutropenic / transplant patients. Pulmonary nodules + halo sign on CT. Galactomannan antigen positive. |
| Central Line-Associated Bloodstream Infection (CLABSI) | Bacterial or fungal. Culture the line. Remove suspected source. |
| Catheter-Related Thrombophlebitis | Erythema, tenderness along vein. May be infected. |
| Drug Fever | Diagnosis of exclusion. Fever with no source. |
5. Clinical Presentation
Symptoms
Signs
| Finding | Notes |
|---|---|
| Fever | Often persistent despite antibiotics. May be absent in immunocompromised. |
| Sepsis Signs | Tachycardia, hypotension, tachypnoea, confusion. |
| CVC Site Infection | Erythema, purulence (not always present). |
| Skin Lesions | Non-tender, erythematous macronodular papules (esp. neutropenic patients). |
| Chorioretinitis / Endophthalmitis | Fluffy white retinal lesions on fundoscopy. Eye pain, visual changes. |
Syndromes of Invasive Candidiasis
| Syndrome | Notes |
|---|---|
| Candidemia (Primary) | Blood culture positive. Often CVC-related. |
| Catheter-Associated Candidemia | Most common form. Remove line. |
| Deep-Seated Candidiasis | Organ involvement: Hepatosplenic (neutropenic recovery), Endocarditis, Endophthalmitis, Osteomyelitis. |
| Chronic Disseminated Candidiasis (Hepatosplenic) | Neutropenic patients during recovery. Microabscesses in liver/spleen. ALP elevated. CT: target lesions. |
| Candida Endocarditis | Vegetations on echocardiogram. Prosthetic valves or IVDU. Surgery often required. |
| Candida Endophthalmitis | Haematogenous seeding. Eye pain, floaters, visual loss. Ophthalmology emergency. |
Often non-specific, especially in critically ill patients.
Common presentation.
Fever
May be only sign. Persistent fever despite broad-spectrum antibiotics.
Sepsis/Shock
Hypotension, tachycardia, altered mental status.
Signs of Deep-Seated Infection
Eye symptoms (if endophthalmitis), heart murmur (if endocarditis), skin lesions (macronodular lesions – rare but suggestive).
6. Investigations
Blood Cultures
- Essential. Gold standard for candidemia.
- Positive in ~50-70% of cases. Lower sensitivity for deep-seated infection without candidemia.
- Time to Positivity: May take 2-5 days (longer than bacterial cultures).
Biomarkers
| Biomarker | Notes |
|---|---|
| 1,3-Beta-D-Glucan (BDG) | Component of fungal cell wall. Elevated in Candida, Aspergillus, Pneumocystis. Sensitivity 70-80%. Non-specific. |
| Mannan / Anti-Mannan Antibodies | Candida-specific. Less widely used. |
| T2Candida Panel | Rapid PCR-based blood test. Detects 5 main Candida species directly from blood (2-3 hours). Increasing use. |
Imaging
- CT Abdomen: If hepatosplenic candidiasis suspected (target lesions in liver/spleen).
- Echocardiogram: If endocarditis suspected (new murmur, vegetation).
Eye Examination
- Dilated Fundoscopy by Ophthalmology: MANDATORY for all patients with candidemia. Detect endophthalmitis.
- Timing: Within 1 week of diagnosis (ideally within days of starting treatment).
7. Management
Management Algorithm
SUSPECTED INVASIVE CANDIDIASIS
(Risk factors + Fever not responding to Abx)
↓
BLOOD CULTURES x2 (Peripheral + CVC)
+/- 1,3-Beta-D-Glucan
↓
START EMPIRICAL ANTIFUNGAL?
┌────────────────┴────────────────┐
HIGH SUSPICION LOW SUSPICION
(Sepsis, Multiple RFs) (Wait for cultures)
↓
ECHINOCANDIN IV
(Anidulafungin, Caspofungin,
Micafungin)
↓
BLOOD CULTURES CONFIRM CANDIDA
↓
SPECIES IDENTIFICATION + SENSITIVITIES
↓
SOURCE CONTROL
- REMOVE ALL CENTRAL LINES
- CT/Imaging for deep-seated source
- Drain collections
↓
OPHTHALMOLOGY REVIEW (Eye Exam)
- Dilated Fundoscopy
- Rule out Endophthalmitis
↓
CONTINUE IV ECHINOCANDIN
(Until cultures -ve + clinical improvement)
↓
STEP-DOWN ORAL THERAPY?
(If C. albicans or sensitive species,
patient stable, CVC removed, no
metastatic complications)
→ FLUCONAZOLE 400mg PO daily
↓
DURATION:
- Candidemia (uncomplicated): 14 days
from FIRST NEGATIVE BLOOD CULTURE
- Endophthalmitis: 4-6 weeks
- Endocarditis: 6+ weeks + surgery
Antifungal Therapy
| Agent | Class | Notes |
|---|---|---|
| Anidulafungin, Caspofungin, Micafungin | Echinocandins | First-line for invasive candidiasis. Fungicidal. Active against most Candida spp including glabrata. IV only. |
| Fluconazole | Azole | Step-down therapy if species sensitive (C. albicans, C. parapsilosis). PO or IV. C. krusei intrinsically resistant. C. glabrata often resistant. |
| Voriconazole | Azole | Broader spectrum. Used for C. glabrata (if fluconazole-resistant) or mixed fungal infection. |
| Amphotericin B (Liposomal) | Polyene | Reserved for resistant Candida (C. auris), intolerance/failure, CNS/eye involvement. Nephrotoxic. |
Source Control (Critical)
- Remove ALL CVCs: In all patients with candidemia, remove or exchange CVCs even if no obvious catheter infection. Biofilm on catheter is a source.
- Drainage of Abscesses: CT-guided or surgical.
- Cardiac Surgery: If Candida endocarditis (vegetation, prosthetic valve).
Duration of Therapy
| Syndrome | Duration |
|---|---|
| Candidemia (uncomplicated, CVC-associated) | 14 days from first negative blood culture AND resolution of symptoms. |
| Deep-seated infection (no endocarditis/eye) | ≥4 weeks. |
| Endophthalmitis | 4-6+ weeks (intravitreal antifungal may be needed). |
| Endocarditis | ≥6 weeks + surgical valve replacement. |
8. Candida auris
Special Considerations
- Multi-Drug Resistant: Often resistant to Fluconazole (90%), Amphotericin B (30%), Echinocandins (5%).
- Transmissible: Person-to-person in healthcare settings. Survives on surfaces for weeks.
- Infection Control: Isolate patient. Enhanced cleaning. Screen contacts.
- Treatment: Echinocandin first-line. Check sensitivities. Combination therapy may be needed.
9. Complications
| Complication | Notes |
|---|---|
| Candida Endophthalmitis | Eye involvement. Causes blindness if untreated. Mandatory eye exam. |
| Candida Endocarditis | Vegetations. Prosthetic valve. Requires surgery + prolonged antifungals. High mortality. |
| Hepatosplenic Candidiasis | Microabscesses. Neutropenic recovery. Prolonged antifungal therapy. |
| Septic Shock | ~20% of candidemia. Aggressive resuscitation + source control. |
| Metastatic Complications | Osteomyelitis, Meningitis, Renal abscess. |
| Death | Mortality 30-50% in ICU patients. |
10. Prognosis and Outcomes
- Attributable Mortality: 20-25% (additional to underlying disease mortality).
- Key Prognostic Factors: Early appropriate antifungal therapy, Source control (line removal), Species (C. auris, C. glabrata worse), Severity of underlying illness.
- Clear Blood Cultures: Repeat daily until negative. Time to clearance affects prognosis.
11. Evidence and Guidelines
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| Candidiasis Guidelines | IDSA (2016) | Echinocandin first-line. Remove CVCs. Ophthalmology review. |
| ESCMID | ESCMID (2020) | Similar. Emphasises BDG for early diagnosis. |
Landmark Evidence
- Echinocandins superior to Fluconazole as initial therapy (Multiple RCTs).
- Line removal associated with improved outcomes.
12. Patient and Layperson Explanation
What is Invasive Candidiasis?
It is a serious fungal infection where Candida (a type of yeast normally found on skin and in the gut) gets into the bloodstream or internal organs. This usually happens in people who are very sick in hospital, especially those with drips (central lines), receiving antibiotics, or after major surgery.
Is it serious?
Yes. It can be life-threatening if not treated quickly. The mortality rate is significant, so we start treatment early.
How is it treated?
We give you strong antifungal medications through your vein (IV). We will also remove any drips (central lines) as these can be the source of infection. An eye doctor will check your eyes because the infection can spread there.
Can it be prevented?
In hospital, we try to remove unnecessary drips as soon as possible, avoid overusing antibiotics, and follow strict hygiene measures to prevent infection.
13. References
Primary Sources
- Pappas PG, et al. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62(4):e1-e50. PMID: 26679628.
- Cornely OA, et al. ESCMID guideline for the diagnosis and management of Candida diseases 2012. Clin Microbiol Infect. 2012;18(Suppl 7):1-8.
14. Examination Focus
Common Exam Questions
- First-Line Therapy: "What is first-line antifungal for candidemia?"
- Answer: Echinocandin (Anidulafungin, Caspofungin, Micafungin).
- Source Control: "What must be done in all patients with candidemia?"
- Answer: Remove Central Venous Catheters.
- Mandatory Investigation: "What specialist review is mandatory for all candidemia patients?"
- Answer: Ophthalmology (Dilated Fundoscopy to exclude endophthalmitis).
- Resistant Species: "Which Candida species is intrinsically Fluconazole-resistant?"
- Answer: Candida krusei.
Viva Points
- C. auris: Be able to discuss multi-drug resistance, infection control measures, and treatment challenges.
- Duration of Therapy: 14 days from first negative blood culture for uncomplicated candidemia.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.