Candidiasis¶
Chapter 222 | Part 5: Infectious Diseases
KEY CLINICAL POINTS¶
- Candida species are common nosocomial pathogens, with C. albicans historically dominant but non-albicans species (e.g., C. glabrata, C. auris) increasingly prevalent due to antifungal resistance.
- C. auris is an emerging multidrug-resistant species associated with outbreaks in healthcare settings, with resistance to all three antifungal classes (azoles, echinocandins, polyenes).
- Diagnosis of disseminated candidiasis requires differentiation between colonization and invasive infection, with key indicators including ocular lesions, macronodular skin lesions, and positive blood cultures.
- Treatment of candidemia typically involves echinocandins as first-line therapy, with fluconazole or newer triazoles used for non-neutropenic patients. C. auris infections require echinocandins due to resistance patterns.
- Prophylaxis with fluconazole is recommended for high-risk patients (e.g., neutropenic patients, HIV patients with CD4 <100/ µ L), but resistance concerns limit its universal use.
1. DEFINITION & OVERVIEW¶
Candidiasis encompasses infections caused by Candida species, ranging from superficial mucocutaneous infections to life-threatening disseminated disease. The genus includes >150 species, with C. albicans, C. glabrata, C. tropicalis, and C. auris being the most clinically relevant. Disseminated candidiasis occurs when Candida enters the bloodstream, leading to systemic infection and organ involvement.
Table 222-1 Well-Recognized Factors and Conditions Predisposing to Hematogenously Disseminated Candidiasis¶
| Risk Factor | Description |
|---|---|
| Antibacterial agents | Broad-spectrum antibiotic use disrupts normal flora |
| Indwelling intravenous catheters | Central venous catheters increase bloodstream entry risk |
| Hyperalimentation fluids | Parenteral nutrition promotes candidemia |
| Indwelling urinary catheters | Urinary tract colonization risk |
| Parenteral glucocorticoids | Immunosuppression increases susceptibility |
| Severe burns | Skin barrier disruption |
| CARD9 deficiency (central nervous system) | Genetic defect in innate immunity |
| Abdominal and thoracic surgery | Surgical trauma and immunosuppression |
| Cytotoxic chemotherapy | Neutropenia and immunosuppression |
| Immunosuppressive agents for organ transplantation | Post-transplant immunosuppression |
| Respirators | Ventilator-associated colonization |
| Risk Factor | Description |
|---|---|
| Myeloperoxidase deficiency | Impaired neutrophil function |
| Neutropenia | Reduced host defense |
| Low birth weight (neonates) | Immature immune system |
| Diabetes | Hyperglycemia promotes fungal growth |
1.1 Clinical Spectrum¶
Mucocutaneous infections (thrush, vulvovaginal candidiasis) are common in immunocompromised patients. Disseminated candidiasis involves hematogenous spread to organs (liver, spleen, CNS), with C. auris associated with high mortality due to multidrug resistance.
1.2 Pathogenesis¶
Candida adheres to mucosal surfaces, forms biofilms, and invades tissues via breaches in epithelial barriers. Immune evasion mechanisms include capsule formation, resistance to host defenses, and drug efflux pumps.
2. EPIDEMIOLOGY¶
Candida species are among the most common nosocomial pathogens, particularly in developed countries. C. auris has emerged as a global health threat, with outbreaks in healthcare facilities. Risk factors include immunosuppression, broad-spectrum antibiotics, invasive devices, and prolonged hospitalization.
Table 222-2 Typical Decision-Making Steps in the Diagnosis of C. auris¶
| No. | Method | Database/Software | Initial Finding | Confirmation |
|---|---|---|---|---|
| 1. | Bruker Biotyper MALDI-TOF | RUO libraries | C. auris | C. auris |
| 1. | bioMérieux VITEK MS MALDI-TOF | RUO library | C. auris | C. auris |
| 1. | IVD library (v3.2) | C. auris | C. auris | C. auris |
| 1. | Older IVD libraries | C. haemulonii | C. auris possible: Needs further workup | |
| 3. | VITEK 2 YST Software version 8.01 | C. auris | C. auris confirmed | |
| 3. | Older versions | C. haemulonii | C. auris possible: Needs further workup | |
| 4. | API 20C | Rhodotorula glutinis, if characteristic red color absent | C. auris possible: Needs further workup | |
| 5. | API ID 32C | C. intermedia | C. auris possible: Needs further workup | |
| 7. | MicroScan | C. lusitaniae | Can rule out C. lusitaniae, C. guilliermondii, and C. parapsilosis. |
| No. | Method | Database/Software | Initial Finding | Confirmation |
|---|---|---|---|---|
| 9. | GenMark ePlex BCID-FP Panel | C. auris | C. auris confirmed |
2.1 Global Trends¶
Incidence of deep-organ candidiasis has risen due to advances in healthcare (e.g., chemotherapy, immunosuppression). C. auris has spread to >50 countries, with resistance to all antifungal classes.
2.2 Demographics¶
Most common in immunocompromised patients (e.g., HIV, neutropenic patients, transplant recipients). Neonates and elderly are at higher risk for disseminated disease.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Candida species are opportunistic pathogens that exploit host immunosuppression. C. auris exhibits unique virulence factors, including biofilm formation, drug efflux pumps, and resistance to high temperatures and saline concentrations.
Table 222-5 Typical MICs of Available Antifungal Drugs for C. auris¶
| Drug | TENTATIVE RESISTANCE BREAKPOINTsa | MIC RANGE, mg/mL | MIC 50 | MIC 90 |
|---|---|---|---|---|
| Amphotericin B | ‡2 | 0.06–8 | 0.5–1 | 2–4 |
| Fluconazole | ‡32 | 0.12–‡64 | ‡64 | ‡64 |
| Itraconazole | N/A | 0.032–2 | 0.06–0.5 | 0.25–1 |
| Posaconazole | N/A | 0.015–16 | 0.016–0.5 | 0.125–2 |
| Caspofungin | ‡2 | 0.03–16 | 0.25–1 | 1–2 |
| Micafungin | ‡4 | 0.015–8 | 0.125–0.25 | 0.25–2 |
3.1 Virulence Factors¶
C. auris produces biofilms, adheres to surfaces via SCF1 adhesin, and resists host defenses through capsule formation and drug efflux. It thrives in harsh environments (42°C, 10% saline).
3.2 Antifungal Resistance¶
C. auris exhibits resistance to azoles, echinocandins, and polyenes. Resistance mechanisms include ERG11 mutations, overexpression of efflux pumps, and lipid composition changes.
4. CLINICAL FEATURES¶
Clinical manifestations vary from superficial infections (thrush, vulvovaginal candidiasis) to disseminated disease with systemic symptoms. Ocular involvement (endophthalmitis) and macronodular skin lesions are hallmark signs of disseminated infection.
Table 222-3 Treatment of Mucocutaneous Candidal Infections¶
| Disease | Preferred Treatment | Alternatives |
|---|---|---|
| Cutaneous | Topical azole | Topical nystatin |
| Disease | Preferred Treatment | Alternatives |
|---|---|---|
| Oral (thrush) | Fluconazole tablets (100–200 mg/d) | Clotrimazole, nystatin |
| Esophageal | Fluconazole tablets (100–200 mg/d) | Caspofungin, micafungin, amphotericin B |
4.1 Mucocutaneous Infections¶
Oral thrush presents as white patches; vulvovaginal candidiasis causes pruritus and discharge. These are common in immunocompromised patients and antibiotic users.
4.2 Disseminated Disease¶
Systemic symptoms include fever, weight loss, and organ-specific manifestations (e.g., CNS involvement, renal failure). Ocular involvement (endophthalmitis) is a critical complication.
5. DIFFERENTIAL DIAGNOSIS¶
Differential diagnosis includes other fungal infections (e.g., aspergillosis, cryptococcosis) and bacterial infections. C. auris must be distinguished from other Candida species using molecular methods.
5.1 Confounding Factors¶
Colonization vs. infection, drug-resistant strains, and atypical presentations (e.g., immune reconstitution inflammatory syndrome) complicate diagnosis.
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnosis involves clinical evaluation, imaging, and laboratory tests. β -glucan testing and molecular methods (MALDI-TOF, sequencing) are critical for C. auris identification.
Table 222-4 Agents for the Treatment of Disseminated Candidiasis¶
| Agent | Route of Administration | Dosea | Comment |
|---|---|---|---|
| Amphotericin B deoxycholate | IV only | 0.5–1.0 mg/kg daily | Mostly replaced by lipid formulations |
| Liposomal amphotericin B | IV only | 3.0–5.0 mg/kg daily | Less toxic than deoxycholate |
| Posaconazole | IV and oral | 300 mg/d (IV), 200 mg tid (oral) | Approved for prophylaxis |
| Fluconazole | IV and oral | 400 mg/d | Most commonly used |
| Voriconazole | IV and oral | 400 mg/d | Multiple drug interactions |
| Caspofungin | IV only | 50 mg/d | First-line for C. auris |
| Anidulafungin | IV only | 100 mg/d | Echinocandin class |
| Micafungin | IV only | 100 mg/d | Echinocandin class |
| Rezafungin | IV only | 400 mg loading dose, 200 mg weekly | Newer echinocandin |
6.1 Diagnostic Tests¶
Blood cultures, CSF analysis, and imaging (e.g., MRI for CNS involvement) are essential. β -glucan testing has ~90% negative predictive value for invasive disease.
6.2 Molecular Diagnostics¶
MALDI-TOF MS, sequencing of ITS regions, and ePlex BCID-FP panels enable rapid identification of C. auris and other Candida species.
7. MANAGEMENT & TREATMENT¶
Treatment depends on infection severity and patient risk factors. Echinocandins are first-line for disseminated candidiasis, while azoles are used for mucocutaneous infections.
Table 222-6 CDC-Recommended Echinocandin Doses for C. auris¶
| Drug | Adults (>2 Months) | Children (<2 Months) |
|---|---|---|
| Caspofungin | Loading dose 70 mg IV, then 50 mg IV daily | Loading dose 70 mg/m2/day IV, then 50 mg/m2/day IV |
| Micafungin | 100 mg IV daily | 2 mg/kg/day IV with option to increase to 4 mg/kg/day in children ‡40 kg |
7.1 Antifungal Therapy¶
Echinocandins (caspofungin, micafungin) are preferred for C. auris. Fluconazole is used for non-neutropenic patients. Voriconazole and posaconazole are alternatives for resistant strains.
7.2 Surgical Intervention¶
Removal of infected devices (e.g., catheters) and excision of infected tissue (e.g., valves) are critical for localized infections.
8. PROGNOSIS & COMPLICATIONS¶
Prognosis varies with immune status and treatment response. Complications include CNS involvement, ocular damage, and drug-resistant infections. Mortality rates for C. auris candidemia range from 30–60%.
8.1 Ocular Complications¶
Candida endophthalmitis can lead to blindness. Partial vitrectomy and antifungal therapy (e.g., amphotericin B + flucytosine) are critical for visual preservation.
8.2 Immune Reconstitution Syndrome¶
ART initiation in HIV patients may trigger immune reconstitution inflammatory syndrome (IRIS), requiring corticosteroid use to manage inflammation.
9. SPECIAL CONSIDERATIONS¶
Prophylaxis with fluconazole is recommended for high-risk patients (e.g., neutropenic patients, HIV patients with CD4 <100/ µ L). C. auris colonization requires strict infection control measures.
9.1 Prophylaxis¶
Fluconazole (400 mg/d) is used for neutropenic patients and HIV patients. Posaconazole is approved for prophylaxis in neutropenic patients.
9.2 Infection Control¶
C. auris is persistent on surfaces and requires rigorous environmental cleaning. Hand hygiene and isolation precautions are essential to prevent spread.
10. KEY POINTS & CLINICAL PEARLS¶
- C. auris is a multidrug-resistant Candida species with high mortality in disseminated infections.
- Diagnosis requires molecular methods (MALDI-TOF, sequencing) due to phenotypic similarity to other Candida species.
- Echinocandins are first-line therapy for C. auris, while azoles are used for mucocutaneous infections.
- Prophylaxis with fluconazole is recommended for high-risk patients but must balance resistance risks.
- Ocular involvement (endophthalmitis) requires prompt surgical intervention and antifungal therapy.