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Candida Species
- C. albicans â most common; mostly antifungal-sensitive
- C. glabrata â fluconazole-resistant often (esp. higher doses or alternative needed)
- C. parapsilosis â neonatal + line; some echinocandin variable
- C. tropicalis â neutropenic invasive
- C. krusei â intrinsic fluconazole resistance
- C. auris â multi-drug resistant; nosocomial outbreaks (Ch 252)
- C. dubliniensis â HIV oral candidiasis (mimics albicans)
Risk Factors for Invasive Candidiasis
- ICU stay > 5 days
- Central venous catheter
- Broad-spectrum antibiotics
- Parenteral nutrition
- Abdominal surgery (especially with perforation)
- Neutropenia (chemotherapy, transplant)
- Hemodialysis
- Diabetes mellitus
- Severe burns
- Pre-existing colonization at multiple body sites
Diagnosis
- Mucocutaneous: clinical (oral thrush, vaginal discharge with KOH wet mount)
- Invasive: blood cultures (50%+ sensitivity in candidemia), tissue biopsy + cultures
- β-D-glucan: serum marker â elevated in invasive candidiasis (and PJP, Aspergillus); not specific
- T2 Magnetic Resonance (Candida T2MR): rapid culture-independent diagnosis (FDA 2014)
- PCR: emerging
- Ophthalmologic exam: all candidemia patients (chorioretinitis risk â IDSA recommendation)
Treatment
Mucocutaneous
- Oropharyngeal: clotrimazole troches, nystatin swish-and-swallow, fluconazole 100-200 mg à 7-14 d
- Esophageal: fluconazole 200-400 mg à 14-21 d; echinocandin or AmB if refractory / severe
- VVC: fluconazole 150 mg PO à 1 (or topical azoles); recurrent (⥠4/yr) â fluconazole weekly suppression
- Severe / recurrent / non-albicans: ibrexafungerp (oral, FDA 2021) alternative
Invasive
- Echinocandin first-line (caspofungin, micafungin, anidulafungin, rezafungin)
- Step-down to fluconazole if azole-sensitive species (after stable + neg cultures + species ID)
- Voriconazole if C. krusei or specific scenarios
- AmB if severe / endocarditis / specific indications
- Duration: 14 days after first negative blood culture (candidemia) + clinical improvement
- Source control: line removal, debridement, surgery
Special
- C. krusei: echinocandin (intrinsic fluconazole R)
- C. auris: echinocandin (but resistance growing; AST + ID consult)
- C. glabrata: echinocandin preferred; fluconazole if high-dose + sensitive
- C. parapsilosis: fluconazole or echinocandin (some echinocandin resistance)
IDSA Recommendations
- Ophthalmologic exam within 1 week of candidemia diagnosis (chorioretinitis 9-37%)
- Repeat blood cultures until clear
- Line removal if catheter-related
- TEE for persistent candidemia + endocarditis suspicion
1ïžâ£ Candida Species + Pathogenesis
Candida albicans
- Most common Candida species in humans
- Commensal of GI + GU + skin
- Dimorphic (yeast + hyphal forms â virulence factor)
- Becomes pathogenic with immune compromise, mucosal disruption, antibiotic flora changes
Other Common Species
C. glabrata
- Small yeast, no pseudohyphae
- High fluconazole resistance (often need higher dose or echinocandin)
- Common in immunocompromise + elderly + diabetic
- Some echinocandin resistance emerging (FKS gene mutations)
C. parapsilosis
- Common in neonatal + ICU + line infections
- Variable echinocandin susceptibility â sometimes higher MIC
- Pediatric concern
- Adheres to plastic surfaces (catheters)
C. tropicalis
- Common in neutropenic + leukemia
- Often invasive + disseminated
C. krusei
- Intrinsic fluconazole resistance (do not use fluconazole)
- Voriconazole or echinocandin
- Important consideration in azole-prophylaxis breakthrough
C. auris (Ch 252)
- WHO critical priority pathogen
- Often multi-drug resistant (fluconazole + amphotericin + echinocandin variable)
- Nosocomial outbreaks
- 2024 + ongoing increasing cases globally
C. dubliniensis
- Mimics C. albicans; HIV oral candidiasis common cause
- Fluconazole-sensitive often
2ïžâ£ Pathogenesis + Risk Factors
Mucocutaneous
- Disruption of mucosal barrier
- Immunosuppression (HIV, steroids, immunocompromise)
- Antibiotic use (flora alteration)
- Diabetes mellitus
- Inhaled corticosteroids (oral thrush)
- Pregnancy + OCs (VVC)
- Dentures, smoking, hyposalivation
Invasive
- Central venous catheter (especially long-term TPN)
- Broad-spectrum antibiotics (alters flora)
- ICU stay prolonged
- Parenteral nutrition
- Abdominal surgery + GI perforation
- Neutropenia (chemotherapy, transplant, leukemia)
- Hemodialysis
- Severe burns
- Pre-existing colonization at multiple body sites (multifocal colonization predicts invasive)
- Diabetes mellitus (severe)
- IDU (endocarditis)
3ïžâ£ Mucocutaneous Candidiasis
Oropharyngeal Candidiasis (âThrushâ)
Risk
- HIV CD4 < 200 (AIDS-defining at < 200)
- Inhaled corticosteroids (e.g., asthma inhalers)
- Dentures + denture stomatitis
- Diabetes
- Post-antibiotic
- Chemotherapy / immunocompromise
- Hyposalivation (Sjögrenâs, radiation)
- Infants (transient, normal)
- Older adults (decreased immunity)
Diagnosis
- Clinical (visible plaques)
- KOH preparation: budding yeast + pseudohyphae
- Culture rarely needed (clinical Dx)
Treatment
- Mild:
- Clotrimazole troches 10 mg 5Ã/d à 7-14 d
- Nystatin swish-and-swallow 100,000 U/mL à 5 mL qid à 7-14 d
- Miconazole buccal tablet
- Moderate:
- Fluconazole 100-200 mg PO Ã 7-14 d
- Refractory / Severe:
- Fluconazole 200-400 mg
- Itraconazole solution
- Posaconazole
- IV echinocandin
- Amphotericin B oral suspension (rare)
- HIV: initiate / optimize ART (immune recovery)
Esophageal Candidiasis
Risk
- HIV CD4 < 100 (AIDS-defining)
- Immunocompromise
- Sometimes inhaled steroids (mild)
Clinical
- Odynophagia (painful swallowing)
- Dysphagia
- Retrosternal pain
- Often concurrent oral thrush
- Esophageal ulceration
Diagnosis
- Clinical (especially HIV+ with oral thrush + odynophagia â empirical Tx)
- EGD if refractory or unclear (white plaques, ulcers, biopsy + culture)
- Differential: HSV (small punched-out ulcers), CMV (large linear ulcers), pill esophagitis, reflux
Treatment
- Fluconazole 200-400 mg PO daily à 14-21 days (empirical for HIV with thrush)
- Echinocandin or AmB IV if refractory / severe / not tolerating PO
- Posaconazole alternative
- HIV: ART critical
Vulvovaginal Candidiasis (VVC)
Common Causes
- C. albicans (90%)
- C. glabrata (10% â often fluconazole-resistant)
Risk
- Pregnancy
- Oral contraceptives
- Diabetes mellitus (especially uncontrolled)
- Post-antibiotic
- Tight clothing + synthetic underwear
- Vaginal douching
- HIV / immunocompromise
Clinical
- Pruritus (intense)
- Burning + dyspareunia
- White âcottage cheeseâ discharge
- Vulvar erythema + edema
- Satellite lesions in surrounding skin
Diagnosis
- Wet mount with KOH: budding yeast + pseudohyphae
- Vaginal pH 4-4.5 (normal); pH > 4.5 suggests trichomoniasis or BV
- Culture if recurrent / atypical / fluconazole-resistance suspected
Uncomplicated
- Fluconazole 150 mg PO Ã 1 dose
- Topical azoles (clotrimazole, miconazole, tioconazole) Ã 1-7 days
- Ibrexafungerp 300 mg PO Ã 2 doses (Brexafemme, FDA 2021)
- Equivalent efficacy
Complicated (Severe, Pregnant, Recurrent, Non-Albicans)
- Pregnant: topical azole (preferred over fluconazole, especially 1st trimester)
- Severe: fluconazole 150 mg PO q72h à 3 doses
- Recurrent (⥠4 episodes/yr):
- Acute: 3 doses of fluconazole
- Maintenance: fluconazole 150 mg PO weekly à 6 months
- Ibrexafungerp approved for recurrent VVC (Brexafemme)
- Non-albicans (C. glabrata, C. krusei): topical boric acid 600 mg capsule daily à 14 days; ibrexafungerp
Pregnancy
- Topical azoles 7-day course preferred (clotrimazole, miconazole)
- Avoid fluconazole high-dose (teratogenic 1st trimester)
- Single 150 mg fluconazole low-risk in some studies
Cutaneous Candidiasis
Treatment
- Topical azoles (clotrimazole, miconazole) or nystatin
- Keep area dry
- Oral fluconazole if severe / extensive
- Underlying cause (DM, immune status)
Chronic Mucocutaneous Candidiasis (CMC)
Background
- Rare immune defect (often autoimmune polyendocrinopathy syndrome type 1 â APS-1 / APECED)
- AIRE gene mutations
- T cell dysfunction
- Persistent / recurrent mucocutaneous Candida infections
Clinical
- Persistent oral thrush
- Cutaneous candidiasis (often disfiguring)
- Onychomycosis
- Associated endocrinopathies (hypoparathyroidism, adrenal insufficiency)
- Autoimmune phenomena
Treatment
- Long-term azole (fluconazole, itraconazole)
- Immunomodulators
- Address autoimmune conditions
4ïžâ£ Invasive Candidiasis
Candidemia
Background
- Bloodstream infection with Candida species
- Major nosocomial infection (4th most common bloodstream pathogen in USA)
- Mortality 40-60% in severe / late diagnosis
Risk
- Central venous catheter
- Broad-spectrum antibiotics
- Parenteral nutrition
- Abdominal surgery
- ICU stay > 5 days
- Neutropenia
- Hemodialysis
- DM
- Severe burns
- Multifocal colonization
Clinical
- Fever (often only sign)
- Sepsis-like
- Multi-organ involvement in severe (kidney, brain, eyes, skin, heart)
- Endophthalmitis / chorioretinitis (9-37%)
- Skin lesions (small papules)
Diagnosis
- Blood cultures (sensitivity 50%+; multiple sets, growth often within 1-3 days)
- β-D-glucan elevated (also PJP + Aspergillus)
- T2 Candida MR (FDA 2014): rapid (1-2 hr); culture-independent
- PCR of blood (emerging)
- Speciation + AST important
Ophthalmology Recommendation
- All candidemia patients â ophthalmologic exam within 1 week
- Chorioretinitis 9-37% (especially with prolonged candidemia)
- Endophthalmitis sight-threatening
- Intravitreal antifungal if active retinal disease
First-Line
- Echinocandin (caspofungin 70 mg load â 50 mg/d; micafungin 100 mg/d; anidulafungin 200 mg load â 100 mg/d; rezafungin 400 mg load â 200 mg/wk)
- Empirical broader Tx in immunocompromise with mold risk (voriconazole / isavuconazole / liposomal AmB)
Step-Down
- After 5-7 days + clinical improvement + neg cultures + species + AST
- Fluconazole 400 mg/d if azole-sensitive species
Duration
- 14 days after first negative blood culture + clinical resolution (for uncomplicated candidemia)
- Longer for deep-seated infections + endocarditis + endophthalmitis
Source Control
- Central line removal (essential â biofilm)
- Debridement
- Surgery for intra-abdominal source
Salvage
- AmB liposomal
- Combination therapy
Intra-Abdominal Candidiasis
Risk
- Abdominal surgery
- GI perforation
- Pancreatitis (necrotizing)
- Intra-abdominal abscess
- Prolonged hospitalization
Clinical
- Often subacute
- Fever, abdominal pain
- Sometimes only fever in ICU patient
Treatment
- Echinocandin
- Source control (drainage, surgery)
- 14+ days
Disseminated Candidiasis
Skin
- Small erythematous papules (small âspotsâ 5-10 mm)
- Painful sometimes
Hepatosplenic (Chronic Disseminated)
- Post-leukemia chemotherapy
- Multifocal liver + spleen lesions on US/CT
- Difficult to treat
- Long course required (months)
- Echinocandin + azole combination sometimes
Endophthalmitis / Chorioretinitis
- 9-37% of candidemia
- White retinal lesions
- Vitritis + visual decline
- Intravitreal voriconazole or AmB + systemic antifungal
CNS
- Rare
- Neonatal / shunt / steroids
- Lipid-formulation AmB ± flucytosine (penetrates CSF)
- Voriconazole alternative
Endocarditis
Risk
- Prosthetic valve
- IVDU
- Persistent candidemia
Treatment
- Liposomal AmB or echinocandin + flucytosine
- Surgical valve replacement often required
- 6+ weeks IV + chronic suppression with fluconazole
UTI
Background
- Catheter-related primarily
- Asymptomatic candiduria common (donât always treat)
- Symptomatic cystitis + complicated (obstruction, neutropenia, instrumentation): treat
Treatment
- Fluconazole preferred (penetrates urine well)
- AmB bladder irrigation rarely used
- Echinocandin NOT preferred (poor urinary concentration)
- Catheter change
Osteomyelitis + Septic Arthritis
- Rare
- Echinocandin à 6-12 months + surgical debridement
5ïžâ£ Special Considerations
C. auris (See Ch 252)
- WHO critical priority pathogen
- Multi-drug resistant
- Nosocomial outbreaks
- Echinocandin first-line (but some R)
- 2024+ ongoing global increase
- Infection control critical
Neonatal Candidiasis
- Premature infants major risk
- C. parapsilosis common
- Echinocandin or fluconazole
- Source control + line removal
Pediatric Candidiasis
- Same principles as adult; weight-based dosing
Pregnancy
- VVC: topical azoles preferred
- Invasive: liposomal AmB or echinocandin
- Avoid high-dose fluconazole 1st trimester
- Voriconazole avoided (teratogenic concern)