Invasive Fungal Infections Flashcards
General Fungal Classifications
- Yeasts: unicellular, reproduce by budding (candida, cryptococcus)
- Molds: multicellular, filamentous colonies (aspergillus, blastolycosis, histoplasmosis)
Rapid Diagnostic Tests of IFIs
- B-D-glucan
- Mannan antigen/Anti-mannan antibody
- Nucleic acid PCR
- Galactomannan
B-D-glucan
- Species: Candida, Aspergillosis, PJP
- Low sensitivity and specificity
- Limitations: Doesn’t detect cryptococcus or zygomycetes, controversy surrounding optimal cutoff value
Mannan/Anti-manna Tests
- Species: Candida species
- Highest sensitivity/specificity when used in combination
- Both tests have better specificity than sensitivity
Nucleic Acid PCR
- Species: Candida species
- High sensitivity and specificity
- Limitations: Using too early may decrease sensitivity
Galactomannan
- Species: Aspergillus and some other molds
- Relatively high sensitivity and specificity
- Limitations: not as sensitive in non-neutropenic patients
Invasive Candidiasis Epidemiology
- Most common IFI
- Usually healthcare associated infections: broad antibiotic use, corticosteroids, dialysis
- 40-50% mortality rate
Candida Auris
- Emerging pathogen
- Behaves more like nosocomial bacteria than traditional fungi
- Drug-resistant and spreads in healthcare facilities
Diagnosis IC Difficulties
- Nonspecific clinical signs/symptoms
- Colonization vs infection
- Physical exam: candida endophthalmitis, skin lesions, muscle soreness
IC Risk Factors
- Central venous catheters
- Candida colonization
- Increasing severity of illness
- Broad spectrum antibiotic use
- Abdominal trauma/surgery
- Dialysis
- Parental nutrition
- Corticosteroids
- Certain surgical patients: recurrent GI perforation, anastomotic leaks, acute necrotizing pancreatitis
Diagnosis Candidiasis
- Blood cultures = gold standard
- 2-3 day turn-around time
- 40-75% false negative rate
Candidemia Treatment Guidelines
- Fluconazole: acceptable in select patients (non-critically ill, no prior triazole therapy)
- Lipid AmB: recommended for suspected azole/echinocandin-resistant candida infections
- Voriconazole: effective but not advantageous over fluconazole
Susceptibility Testing
- Azole Susceptibility: recommended for all blood stream isolates
- Echinocandin Susceptibility: consider for patients previously receiving an echinocandin or with prior C.glabrata or parapsilosis infections
Managing Candidemia
- Remove central venous catheters if possible
- Dilated opthalmological examination
- Repeat blood cultures daily to establish clearance
- Duration of therapy minimally 2 week if no metastatic complications
Aspergillosis Epidemiology
- Ubiquitous mold existing all over world
- Exposed via inhalation
- Most common invasive mold infection
- A. fumigatus is most common species
Aspergillosis Disease Spectrum
- Immunocompetent Hosts: allergic reaction, ABPA
- Immune impairment: chronic necrotizing pulmonary aspergillosis (fungal ball, fibrocavitary aspergillosis)
- Immune compromised: acute, invasive aspergillosis, lower respiratory tract infection and hematogenous dissemination into other tissues
IA Risk Factors
- Prolonged neutropenia (degree and duration)
- Recipients of hematopoietic stem-cell transplants or solid organ transplants (highest after lung transplants)
- HIV Stage 3 (AIDS)
- Chronic granulomatous disease
Radiographic Findings
- Halo sign: solid nodule filling with hemorrhage and edema fluid, earlier sign
- Air-crescent sign: air between infarcted lung and surrounding lung parenchyma, late sign
IPA Treatment Guidelines
- Primary treatment: voriconazole, initiate early in those who are strongly suspected of IPA
- Alternatives: Liposomal AmB or isavuconazole
- Echinocandins are NOT recommended as primary therapy
Histoplasmosis Capsulatum
- Dimorphic fungi found in Central and South America
- Most common endemic mycosis causing human infection
- Found from animal droppings and in caves/abandoned houses
Disseminated Histoplasmosis
- Symptomatic patients are usually immunosuppressed
- Chills, fever, anorexia, weight loss
- GI tract: diffuse ulcerations of the mucosa (elevated liver enzymes and serum ferritin, pancytopenia)
- CNS involvement isn’t common
Histoplasmosis Treatment Guidelines
- Chronic/Mild/Moderate: itraconazole is preferred for non-severe
- Alternatives: AmB or fluconazole
- Severe/CNS: Lipid formulation of AmB followed by itraconazole
Coccidioidomycosis
-“Valley Fever”
Manifestations
- Acute pneumonia
- Chronic progressive pneumonia
- Pulmonary nodules and cavities
- Extrapulmonary non-meningeal disease
- Meningitis
Coccidioides + Acute Pneumonia
- Onset: 1-3 weeks after exposure
- Indistinguishable from CAP
- Coccidio Sxs: severe headache and severe pleuritic chest pain, fatigue lasting weeks to month, hilar or paratracheal adenopathy (rarer)
Coccidiodes + Sites of Dissemination
- Extra-pulmonary disease: skin, lymph nodes, bones and joints (uncommon in immunocompetent)
- Meningitis: most severe complication, substantial morbidity (diagnose with serum and CSF cultures)
Coccidiodomycosis Treatment Guidelines
- Initiate treatment in symptomatic individuals/debilitating disease: Fluconazole >=400 mg PO daily
- Alternative: Itraconazole or AmB (or lipid formulation)
- Treatment of asymptomatic pulmonary nodule/cavities isn’t recommended
Cryptococcus Epidemiology
- Neoformans: immunocompromised, pulmonary and meningitis manifestations, worldwide spread
- Gattii: immunocompetent, cryptococcomas and neurologic involvement, prolonged therapy, tropical/subtropical/temperate regions
Cryptococcus Clinical Manifestations
- Blunted immune response
- Main Clinical Presentations: pulmonary infection, cryptococcal meningitis
- Can infect ANY organ of body: cutaneous, eye, prostate, bone, and joint
Cryptococcal Treatment
- Mild-moderate pulmonary disease: Fluconazole
- Severe/Cryptococcal meningitis: AmB PLUS 5-FC x 2 weeks minimum (can replace with L-AmB)
- Maintenance: Fluconazole >= 6 mo
Combination of AmB and 5-FC reduces mortality in meningitis patients
Murcormycoses
- MANY common mucorales
- Diagnosis usually made via pathology
Murcormycoses + Immunocompetent Risk Factors
- Major trauma/contaminated lacerations
- Surgery and use of contaminated materials
- ICU stay with high acuity
- Iron chelation therapy
- Burns
Murcormycoses + Immunocompromised Risk Factors
- Diabetes
- Uremia, metabolic acidosis
- Hematological malignancies
- Stem cell transplant
- Solid organ transplant
- Immunosuppressive drugs
Murcormycoses Clinical Presentation
- Infarction and necrosis of host tissue
- Infection usually begins in nasal turbinates or alveoli
- Poor prognosis, mortality rates up to 90%
Mucormycosis Treatment
- Combine surgical debridement and antifungal therapy
- Drug of choice: L-AmB
- Alternatives: Posaconazole, isavuconazole
- Correction of underlying host abnormalities
- Duration: resolution of signs of infection (usually months)