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
Outbreaks associated with demolition and construction work – heavy contamination of hospital air?
Nosocomial Aspergillosis
Maintain spore-free environment – cleaning, physical barriers
Protect at-risk patients (HEPA filters)
Treatment of Invasive Aspergillosis?
Voriconazole
Amphotericin B (Angioinvasive)
Echinocandins (caspofungin, anuidulafungin)
Surgery – resection of lesion
Stop immunosuppressive therapy, if possible
Prophylaxis (High risk pts. - hematological insufficiency)
Mucormycosis (Mucor/Rhizopus) Risk Factors/Manifestations/Diagnosis/Managment
Risk Factors
Immunocompromised
Diabetes Mellitus
IVDU
Manifestations
ANGIOINVASIVE
Rhinocerebral, Pulmonary, GIT, Cutaneous
Diagnosis: Tissue biopsy- Non-septate hyphae
Management: Amphotericin B, Surgery
(Echinocandins and Azoles have NO activity)
What are non-septate hyphae on tissue biopsy histology diagnostic of?
Mucormycosis (Mucor/Rhizopus)
Cryptococcus Neoformans Risk Factors/Manifestations?
Yeast (encapsulated)
Risk Factors
Soil, avian faeces, rotting vegetation
Immunocompromised
* HIV
* Organ transplant
* Steroids
* Malignancy
Manifestations
Pulmonary
Skin
Bone
Cryptococcal Meningitis: Hematogenous spread from lungs=> Meningitis, confusion, coma, CN palsy
Pathogenesis/Diagnosis/Therapy of Cryptococcal Meningitis
Pathogenesis
Hematogenous spread from lungs => Meningitis, confusion, coma, CN palsy
Diagnosis
Antigen Detection (CrAg) - serum, CSF
India Ink Stain – capsule
CSF
* Elevated opening pressure
* Elevated white cell count (lymphocytes)
* Microscopy and culture
Therapy for Cryptococcal Meningitis
Induction: ** Amphotericin B iv**, Flucytosine po (Minimum 2 weeks)
Consolidation: Fluconazole 400-800mg po (8 weeks)
Maintenance: Fluconazole 200-400mg po (Minimum 1 year)
Raised Intracranial Pressure: Lumbar taps, Ventriculo-peritoneal shunt
Pneumocystis Jiroveci (aka Pneumocystis carinii) Risk Factors
Risk Factors
Disease only in immunocompromised
* HIV (CD4 count <200)
* Malignancy – especially ALL
* Transplant
* Immunosuppressive drugs
* Steroids
Predominantly pulmonary infection => Pneumocystis Pneumonia (PJP)
Clinical Features/Diagnosis/Management of Pneumocystis Pneumonia (PJP)
Clinical Features
Fever
Dry cough
Progressive dyspnoea
Hypoxia
Respiratory failure
Respiratory examination may be normal
Diagnosis
CXR: Bilateral interstitial infiltrates
High resolution CT thorax: Ground-glass attenuation
BAL
* Grocott (silver) stain
* Direct fluorescent antibody staining
* PCR- NOT quantitative
Serum: BD-glucan
Elevated LDH
Managment
Cotrimoxazole – 3 weeks
Steroids – if pO2 < 7.3 mm Hg
Prophylaxis in at-risk groups
Segregation from other immunocompromised patient
