L3 Fungal Infections in the Immunocompromised Flashcards
3 Different Fungal Forms? Examples of each?
- Molds (filamentous) e.g. Aspergillus, Mucor
- Yeasts e.g. Candida, Cryptococcus
- Dimorphic fungi – can exist in mold and yeast forms e.g. Histoplasma
Lab Diagnosis of Fungal Infections?
Microscopy
* Gram stain
* Fungal stains
Culture
* Blood agar
* Sabouraud dextrose agar (SDA)
Antigen detection
* BD-glucan (non-specific, part of cell wall of most fungi but NOT Mucorales) - serum
* Galactomannan (suggestive of Aspergillus) – serum, BAL (useful as usually respiratory)
* Cryptococcal antigen (CrAg (suggestive of Cryptococcus)– serum, CSF
Why do fungal infections occur in IC patients?
Inability to respond normally to infection
- T-cell defects
- B-cell defects (Inadequate antibody production)
- Neutrophil defect or deficiency (Responsible for first line innate defense)
- Mucosal defects (GI Mucosa key for preventing ingested pathogens being absorbed)
Chemo patients prone to mucosal damage - Esp get Candida
Fungal Infections in the immunocompromised?
Candida
Aspergillus: ubiquitous, construction tends to release spores into air
Mucormycetes – Mucor, Rhizopus
Cryptococcus Neoformans
Endemic mycoses - Histoplasma etc.
Pneumocystis Jiroveci
Prevention of fungal infections in the immunocompromised?
Environmental protection
* Cleaning
* Provision of HEPA filtered air
Antifungal prophylaxis
* High risk IC groups (Stem cell, post liver transplant)
Prevention of fungal infections in the immunocompromised?
Environmental protection
* Cleaning
* Provision of HEPA-filtered air
Antifungal prophylaxis
* High risk IC groups (Stem cell, post liver transplant)
Localized Manifestations of Canida Infection: Predispositions/Treatment?
Oropharyngeal
Predisposed by:
* Cellular immunodeficiency e.g., HIV, CD4 <200
* Antimicrobial treatment
* Chemotherapy
* Radiotherapy to head and neck
Treatment
Topical: clotrimazole, miconazole
Oral: azole
Esophagitis
_Manifests as:_Odynophagia (pain on swallowing), retrosternal
Predisposed by:
* Cellular immunodeficiency e.g., HIV, CD4 <200
* Hematological malignancy
* Inhaled corticosteroids ((Bronchiectasis, COPD)
Treatment: Systemic fluconazole (po or iv) – 14-21 days
Invasive Candida infection in Immunocompromised: Manifestation/Treatment
Candida bloodstream infection most common
* Hematological malignancy
* Total parenteral nutrition
* Transplant (SOT and BMT)
* Chemotherapy
* Severely ill in ICU
Treatment of Bloodstream Candida Infections
* Echinocandin initially, modify according to susceptibilities
* Minimum 2 week IV therapy
- Remove line
- Ophthalmology review (rule out endophthalmitis)
- Echocardiogram (rule out fungal endocarditis)
Chronic Disseminated Candidiasis: Risk Factors/Manifestation/Diagnosis/Management
Risk Factors:
Hematological malignancy (Neutropenic for weeks => prone to invasive infection)
Recent neutropenia
Manifestation
* Persistent high fevers
* Right Upper Quadrant pain/discomfort
* Nausea, anorexia, vomiting
* Elevated alkaline phosphatase
Diagnosis
*LESSIONS THROUGHOUT LIVER
* Imaging – CT, MRI
* Biopsy to confirm– granulomata, yeasts
Management
Echinocandin or Amphotericin B
Minimum 6 months, until resolution of lesions on imaging
Management of various forms of Candida Infection
Treatment of Oropharyngeal Candida infection
Topical: clotrimazole, miconazole
Oral: azole
Treatment of Esophagitis
Systemic fluconazole (po or iv) – 14-21 days
Treatment of Bloodstream Candida Infections
Echinocandin initially, modify according to susceptibilities
Minimum 2 week IV therapy
Treatment of Disseminated Candidiasis
Echinocandin or Amphotericin B
–Oral azole as step-down
Minimum 6 months, until resolution of lesions on imaging
Risk Factors for Invasive Aspergillosis infection?
Prolonged neutropenia (> 14 days) e.g., AML
Diabetes mellitus
High dose steroids
Transplant (BMT/ SOT)
HIV (rare < 1%
COVID, influenza
Outbreaks associated with hospital construction/refurbishment
Pathogenesis/Clinical Features of Invasive Aspergillosis?
Pathogenesis
Primary site is lung (Spores inhaled)=> Widespread destructive growth in lung tissue => Invasion of blood vessels (angioinvasive)=> Dissemination to other sites (liver, spleen, kidney, CNS)
Poor prognosis (80% mortality) !!
Clinical Features
Non-specific
Fever – refractory to antibacterials
Cough, Dyspnea, Chest pain
RARE: Skin lesions
Imaging/Diagnosis of Invasive Aspergillosis?
Imaging
CXR – not useful!
High-resolution CT thorax
* Nodules/Cavitation => think fungal
* Consolidation
* Peri-bronchial infiltrates
Highly suggestive of fungal infection:
Halo sign: lucency around the nodule
Air-crescent sign
Diagnosis
Gold Standard is histology (Lung Biopsy) – septate hyphae
Respiratory culture (BAL > sputum): Presence in sputum not indicative of invasive aspergillosis
Galactomannan (antigen) in blood and BAL
Antibodies – WASTE OF TIME, only shows past exposure to infection
What are septate hyphae on tissue biopsy histology diagnostic of?
Invasive Aspergillosis
What are Halo sign and Air-crescent signs on a CT Thorax scan suggestive of?
Invasive Aspergillosis
