Opportunistic Fungi Flashcards
You think your patient has a systemic endemic mycosis. What do you do first?
Serum 1,3-β-D-glucan test
Candida family
- Primarily exist as yeasts, but may form hyphae in invasive infections
-
Candida albicans is the most common human pathogen among them
*
Candida albicans in blood
Source of Candida infection
- Most derived from host’s normal flora (endogenous)
- Typically colonize the GI tract from mouth to rectum, vagina, and skin
Candidiasis risk factors
- Neutropenia
- Broad-specturm antibiotics (opens niche)
- Renal failure requiring dialysis
- Venous catheters
- Parenteral nutrition
Many risk factors associated with ICU patients.
Candida-mediated disease
Superficial:
- Adherent white plaques on mucocutaneous surfaces (thrush)
- Not painful
- Those in warm, moist areas such as armpits, groin, under breasts: intertriginous candidiasis
- Those in babies: diaper rash
- Underlying tissue not damaged, no long-term consequences
Disseminated:
- May present as fever, sepsis, organ dysfunction
- Microabscesses may develop in organs, resulting in organ-specific disorders: meningitis, chorioretinitis, hepatosplenic abscess, vertebral osteomyelitis
- Endocarditis common when prosthetic heart valves are involved
Diagnosis of candidiasis
Mucosal candidiasis: Swipe and culture. Fast and effective
Invasive candidiasis: Blood culture works, but not as sensitive. Biopsy works, but is invasive. Tissue culture more sensitive and specific, same deal. 1,3-β-D-glucan serology is always helpful.
Treatment of candidiasis
Mucosal/intertrigonous candidiasis: Local antifungal cream or powder (often nystatin)
Disseminated candidiasis: Systemic antifungal agent. Usually fluconazole or an echinocandin, liposomal amphotericin B for really bad infections.
Prevention of candidiasis
Mucosal infections in AIDS patients are so common that prophylaxis is indicated, but resistance often develops.
Patients at highest risk, like neutropenic patients or HSC transplant patients, are treated prophylactically with an azole during periods of highest risk.
Cryptococcus neoformans
Environmental yeast which reproduces by budding. Surrounded by an atypically huge polysaccharide capsule when in tissues (but not when in the environment), which prevents phagocytosis.
Source of Cryptococcus infection
- Found worldwide in soil contaminated with bird excrement
- Inhaled into alveoli, then multiplies in lung, often asymptomatically
- Infects 20% immunocompetent, 80% immunodeficient individuals
Cryptococcus neoformans-mediated disease
- May begin as mild lung symptoms, usually in immunosuppressed individuals
- Followed by nervous system symptoms, meningitis, worsening headaches, fever, cranial nerve palsies, mental status changes
- Further non-neuronal dissemination may occur in AIDS patients, who may display diffuse pulmonary infection, skin lesions, and widespread visceral infection
Cryptococcus neoformans-mediated damage
- C. neoformans begins producing its capsule once inside the lung
- Capsule also interferes with Th1 mediators
- Displays substantial neurotropism on second wave replication after migrating through blood
- Further dissemination almost exclusively in AIDS patients, and may appear in visceral organs or skin
Diagnosis of cryptococcal meningitis
- Lumbar puncture and CSF examination by India ink stain
- Latex agglutination test on CSF or serum is highly sensitive and specific
- VERY IMPORTANTLY, cryptococci do NOT express 1,3-β-D-glucan
Treatment of cryptococcosis
- Cryptococcal meningitis:Liposomal amphotericin B and flucytosinefor several weeks,wean to flucytosine alone for several months
- Patients with T-cell defects may require flucytosine for life following infection
- Pulmonary cryptococcosis: Flucytosine alone
Aspergillus
Filamentous fungi that form a mycelium of septate hyphae and reproduce by releasing airborne spores. Most common pathogenic species is Aspergillus fumigatus, but many aspergilli may cause infections.
Source of Aspergillus infection
Ubiquitous in soil, manure, decomposing vegitation throughout the world. May be cultured from soil or water or even air.
Aspergillus-mediated disease
- Aquired by inhalation
- Starts as pulmonary or sinus infection (invasvive pulmonary aspergillosis: fever, pleuritic chest pain, cough, hemoptysis, dyspnea), then dissemiantes into blood
- Usual pathologic picture involves hemorrhagic infarction and necrosis, first in the lung then at disseminated sites
- Acute facial pain is the herald of sinus infection
- May develop necrotic skin lesions or brain absecesses (stroke, seizures, mental status changes) following dissemination
- High mortality rate
Aspergillus-mediated damage
- Inhaled into lung, then germinate into hyphae
- Only hyphae are capable of invading other tissues from the lung
- “Branches” straight into and through tissues
- May be dissemianted by invading blood vessel, fracturing hyphae, and implanting somewhere else
- Implants may cause hemorrhage and necrosis wherever they land, including in most organsm, skin, and brain
Diagnosis of aspergillosis
- Culture takes a few days, very effective
- Tissue biopsy important to document invasion, but is not specific to Aspergillus
- 1,3-β-D-glucan serology effective
- Galactomannan serology also effective and more specific
Treatment of aspergillosis
- Voriconazole for most cases
- In particularly bad cases, liposomal amphotericin B and echinocandins used
- Because mortality rate is high, treatment should be started immediately based on clinical symptoms and CT scan
Mucorales / Zygomycetes
- Molds that differ from Aspergillus in that their hyphae are broader and aseptate
- Angioinvasive in similar manner to Aspergillus
- Major groups are Rhizopus and Mucor
Source of Mucorale infection
Similar to Aspergillus, common environmental organisms
Mucorale-mediated disease
- Acquired by inhalation or through skin lesions
- Risk factors: hematologic malignancies, neutropenia, corticosteroids, diabetes mellitus
- Presents in diabetics as rhino–orbital–cerebral mucormycosis: fungi spread from nares and sinuses into the palate, orbit, and soft tissues of the face, then invade the cavernous sinus and brain.
- Pulmonary and disseminated zygomycosis occur more often in leukemics who are neutropenic and mimic invasive aspergillosis.
Diagnosis of Mucorales
- Detected by culture
- Do NOT produce 1,3-β-D-glucan
Treatment of mucormycosis
- Liposomal amphotericin B
- Aggressive surgical debridement of infected or necrotic tissue
Pneumocystis carinii
- Has never been grown in culture, resulting in a lot of confusion and unknowns
- Sequence analysis reveals that the organism is a fungus
Source of Pneumocytsis infection
- Presumably inhaled from environment
- No known ecological niche
- Most people asymptomatically infected early in life, symptoms only occur in immunosuppressed individuals
Pneumocysis-mediated disease and damage
- Pneumocysis pneumonia is the single most common disease in untreated AIDS patients
- Organism rarely ever found outside of the lungs
- Alveoli filled with foamy proteinaceous material, desquamated alveolar epithelial cells, and small organisms
- Dyspnea, dry cough, fatigue, mild or absent fever, hypoxemia
- Bilateral diffuse lung infiltrate on chest X-ray
Diagnosis of pneumocystis pneumonia
- Demonstration of organism on silver stain or immunofluorescence in respiratory samples (lavage, sputum, biopsy)
- PCR for known Pneumocystis genes
- 1,3-β-D-glucan serology
Treatment of pneumocystis pneumonia
Trimethoprim/sulfamethoxazole
Also a highly effective prophylactic measure in at-risk populations (basically AIDS patients)
