Unit 4 - Pulmonary Fungal Infections; Opportunistic Mycoses Flashcards
what do opportunistic mycoses diseases and severity depend on
depend on patient’s condition
- key one is prolonged neutropenia
- must treat underlying problem and infection itself
what is the organism associated with Cryptococcus?
Cryptococcus neoformans (esp. causes meningitis)
- environmental, found worldwide in soil contaminated with bird droppings (esp. pigeon)
- oval, budding yeast
- not thermally dimorphic
- narrow-based bud and wide polysaccharide capsule (diagnostic)
- no human-to-human transmission
what are the 5 serotypes of Cryptococcus?
A, D, AD = neoformans
B, C = gatti (in litter under eucalyptus –> severe disease, esp. if immunocompetent in west coast)
what is the sexually reproducing form of C. neoformans?
mold-like form in environment
what is the pathogenesis of Cyrptococcus?
transmitted by inhalation?
- lung infection may be asymptomatic or lead to (rare) pneumonia
- immunosuppression (esp. AIDS) is predisposing, but not required for hematogenous dissemination (via alveolar MP)
- dissemination leads to cryptococcal meningitis w/ skin nodules (esp. if AIDS)
- combo of host immunosuppression and fungal immune modulation blunts inflammatory response to infection
what happens if immunocompetent person is infected with Cryptococcus?
keep it in lungs, raise successful immune response
what are virulence factors of C. neoformans?
capsule, melanin in cell wall (antiphagocytic), phospholipase B for invading tissue
how does one diagnose cryptococcus?
- history: steroids, malignant disease, transplant, HIV+
- skin: take biopsies of nodules
- pulmonary: range from asymptomatic to ARDS, cough and chest pain common
- cryptococcus + HIV: fever, cough, headache, weight loss, +cultures (CSF, blood, urine)
- CNS: subacute meningitis or meningoencephalitis, antifungal therapy to survive (do CT or MRI)
- misc: prostrate, eyes, medullary cavity of bones
what does meningitis from cryptococcus usually show?
- headache
- altered mental status
- nausea, vomiting
- fever/stiff neck less common (arise from inflammation)
- sensory issues w/ ears/eyes
- if not acute pyogenic, may wait for CT/MRI before lumbar puncture
what are cryptococcomas?
focal neurologic defects due to cryptococcus
what does blunted inflammatory response mean in cryptococcus?
presentation is late in disease; complicates diagnosis
what does labwork show in cryptococcus?
- CSF: stain w/ India ink to observe yeast w/ wide capsule
- other stains (from biopsy): methenamine silver, period acid-Schiff, mucicarmine
- culture from spinal fluid for mucoid colonies on agar
- serologic tests: “crag” for soluble cryptococcal Ag in blood and CSF
- routine bloodwork may be normal (low inflammation)
what is treatment for cryptococcus if you have meningitis or cyrptococcoma?
amphotericin B (liposomal if kidney issues) plus flucytosine for 2 weeks + 10+ weeks of fluconazole -in AIDS patients, use fluconazole for long-term suppression; clearance may not be an option
what is treatment for cryptococcus if you have prostate problems?
fluconazole
what is treatment for cryptococcus if you have AIDS?
fluconazole for long-term suppression; clearance may not be option
what is treatment for cryptococcus if you have pulmonary cryptococcosis?
if immunocompetent, may not need treatment; can use 6-12 mo fluconazole or itraconazole
what is treatment for cryptococcus if you have skin/bone/other involvement?
amphotericin B
what should you do during treatment of cryptococcosis?
examine CSF weekly to determine progress
- glucose and cell count will return to normal, but PRO anomalies may persist for years
- don’t discontinue therapy until cultures consistently fail
what is the organism involved in Aspergillosis?
Aspergillus fumigatus, niger, flavus, clavatus
- ubiquitous environmental molds (not dimorphic), thus have trouble getting into bloodstream
- septate hyphae with V-shaped branches (diagnostic)
- walls are nearly parallel
- conidia form radiating chains
what are the 4 syndromes that aspergillosis causes?
all caused by the same group of organisms
- allergic bronchopulmonary aspergillosis (ABPA)
- aspergilloma or colonizing aspergilliosis (fungus ball in lung)
- chronic necrotizing pulmonary aspergillosis (CNPA)
- invasive aspergillosis
explain the pathogenesis of aspergillosis?
- widespread on decaying vegetation worldwide
- infectious conidia are airborne
- -colonize abraded skin, burns, cornea, ear, sinuses, lung
- healthy MP can neutrophil response eradicates fungus, but some Aspergillus produce toxic metabolites that inhibit it (as corticosteroids would)
explain what ABPA is
allergic bronchopulmonary aspergillosis
- hypersensitivity to infection of bronchi by aspergillus
- exacerbates asthma, CF (pre-existing)
explain what aspergilloma is?
fungus ball forms at site of cavitary lesion left by past TB, pulmonary mycosis, CF
-can cause lethal pulmonary hemorrhage, life-threatening hemoptysis
what are virulence factors for aspergillus?
- gliotoxin (immunosuppressive)
- toxic metabolites (interfere w/ immune response)
- proteases (invade tissue)
explain what CNPA is?
chronic necrotizing pulmonary aspergillosis; mostly in immunocompromised
-rare, hard diagnosis, best sample is lung fluid aspirate
explain what invasive aspergillosis is?
rapidly progressive invasion of blood vessels in severely immunosuppressed patients or COPD + long-term corticosteroids
- involves infarction, hemorrhage, necrosis (often fatal 30-95%)
- cough, fever, pleuritic chest pain, worsening hypoxemia
- relatively common in severely immunosuppressed patients (5-20%)
what does ABPA show on exam?
- +skin test for aspergillus allergy with asthma or CF
- coughing up brownish bronchial plugs with hyphae
- fever, wheezing, pulmonary infiltrates unresponsive to antibiotics
- hemoptysis
- uncontrolled asthma
- purulent sinus drainage
- X-ray or CT may show “grape bluster” or “hand in mitten” clusters of mucous-clogged bronchi
what does aspergilloma show on exam?
- fungus ball on CXR or CT (mass in cavity) that changes position when sitting up or laying down (air crescent sign)
- doesn’t invade tissue, but can cause dangerous hemoptysis
- cough, fever
- may appear as complication of CNPA or invasive aspergillosis
what does CNPA show on exam?
- subacute pneumonia unresponsive to antibiotics-subacute pneumonia unresponsive to long term antibiotics, ineffective treatment for TB
- history of alcoholism, collagen-vascular disease, chronic granulomatous disease (may find hyphae), COPD, long-term corticosteroids
- fever, cough, night sweats, weight loss
- history of ineffective emperic treatment for TB
- needle biopsy, aspirate fluid if present, for histo and culture
what does invasive aspergillosis show on exam?
- in severely immunosuppressed patients or COPD + long-term corticosteroids
- CT scan abnormal, but variable shows “halo sign” and “ground glass attenuations” –> represents hemorrhage
- fever, cough, dyspnea, pleuritic chest pain, neutropenia, sometimes hemoptysis or worsening hypoxemia
- bronchoscopy, needle biopsy, or open lung biposy for culture and histology
what do aspergillosis cultures show?
from sputum, needle biopsy or bronchoalveolar lavage fluid
- visualize with silver stains
- colonies w/ radiating chains of conidia
what does specifically invasive aspergillosis show on culture?
- septate hyphae branching at acute angles invading tissue
- acute inflammatory infiltrate
- tissue necrosis
- blood vessel invasion
- high serum levels of glactomannan Ag
what does specifically ABPA show on culture?
- high levels of aspergillus-specific IgE
- eosinophilia
- hyphae in mucus w/ degenerating eosinophils
what is treatment for ABPA?
- oral corticosteroids and itraconazole
- consider sinus surgery and/or omalizumab (inhaled steroids, which is unique out of all the apsergilloses)
what is treatment for aspergilloma?
- remove surgically if hemoptysis
- oral itraconazole
what is treatment for invasive or CNPA?
- voriconazole and/or amphotericin B
- -liposomal if kidney issues
- capsofungin may not work
- decrease immunosuppression if possible
- surgical resection considered
what are organisms that cause mucormycosis?
Mucor, Rhizopus, and Absidia
- very rare and lethal; sinus infections may invade brain
- widespread in environment, but not dimorphic
what are underlying risk factors for mucormycosis?
diabetes and neutropenia
what is the pathogenesis of mucormycosis
transmitted by airborne asexual spores; disease only if vulnerable
- invades tissues of patients with reduced immunity (burns, diabetics, leukemia, IV steroids, TNF deficiency, Fe overload)
- neutrophils (innate immunity) are main host defense
- not highly associated with AIDS (CMI may not be critical)
where does mucormycosis proliferate?
walls of blood vessels
- paranasal sinuses, invading brain: poor prognosis, even when cured requires disfiguring surgery
- lungs: harder to diagnose, higher mortality
- gut: harder to diagnose, higher mortality, plus risk of extreme malnutrition
skin: 15% mortality - disseminated: near 100% mortality
- cause infarction and necrosis of tissue downstream from blocked vessel
what is rhinocerebral mucormycosis? exam results?
diabetics may have blocked blood supply to brain
- unilateral retro-orbital headache, facial pain, numbness, fever
- progresses to diplopia and visual loss, reduced consciousness, black pus, necrotic eschars
- CT may be useful to detect sinusitis invading brain
what are wound infections due to mucormycosis important for?
unresponsive to antibiotics
what are lung and GI presentations in mucormycosis?
nonspecific, bronchoalveolar lavage or biopsy are useful
- CT scan of lung for cavitation with air crescent is highly suggestive of fungal infection
- CT scan of gut may show mass
what are cutaneous presentations in mucormycosis?
cellulitis progressing to dermal necrosis and black eschar formation
what does bloodwork show for mucormycosis?
neutropenia, diabetic acidosis, Fe overload
what are useful Ag or CSF tests in mucormycosis?
none
what does mucormycosis biopsy show?
H&E or fungal stains show nonseptate hyphae with broad, irregular walls and branches at right angles, vascular invasion and necrosis, neutrophil infiltration
what does mucormycosis culture show?
colonies with spores contained in sporangium
-hard to culture
what is mucormycosis treatment?
frequently fatal (send to tertiary care facility) b/c diagnostic window is short
- change any pre-existing bandages/splits that could be contaminated
- if diagnosed early, treatment of underlying disorder + liposomal amphotericin B and aggressive surgical removal of necrotic tissue may help
- alternative is posaconazole
- repeated, disfiguring surgery is required for patient survival
what is the mycology of Fusifarium species?
environmentally ubiquitous
- banana-shaped macroconidia
- primarily pathogens of plants (esp. important crops)
- Fusarium solani is most common
what are virulence factors of Fusarium species?
- immunosuppressive mycotoxins
- collagenases and proteases
- ability to adhere to prosthetic material
what are the 3 presentations of Fusarium?
all rare
- mycotoxicosis
- immunocompetent local infection
- immunosuppressed opportunistic infection
explain mycotoxicosis of fusarium?
trichothecene mycotoxins –> alimentary toxic aleukia
-widespread bleeding and immunosuppression with secondary sepsis, often fatal when contaminate wheat
explain immunocompetent local infection for fusarium? treatment?
- skin (burns)
- cornea (contaminated contact lens solution)
- allergic sinusitis (like ABPA)
- colonization of prosthetics and catheters
- treat with amphotericin B, voriconazole, posaconazole
explain immunosuppressed fusarium?
opportunistic infection
- prolonged neutropenia
- long-term use of steroids
- profound T-cell deficiency (hematopoietic stem cell transplant recipients)
- aggressive disseminated infection
what is the pathogenesis of disseminated infection of fusarium?
especially seen if immunosuppressed
- usually invades from sinus or wound site via airborne conidia or nosocomial waterborne transmission
- presents as fungemia with skin lesions
- may seed eye, lung, cause local symptoms there
what are systems commonly affected by disseminated fusarium?
- eye: progress from corneal infection in immunocompetent or seeded from blood in disseminated
- sinus: may be allergic sinusitis in immunocompetent; invasive sinusitis in immunocompromised
- pneumonia: common and resembles aspergillus pneumonia
- skin: localized at wound sites in immunocompetent, but spread and prefer toes if disseminated (gangrenous)
what is fungemia?
positive blood cultures seen more in fusariosis than aspergillosis
- may be seen in immunocompetent patients with central venous catheters
- more commonly in dissemination
how is disseminated disease diagnosed?
combo of skin lesions and positive blood cultures in neutropenic or profoundly T-cell depleted patient
how do you diagnose fusarium?
- take samples from several sites for multiple cultures on fungal media (grows easily)
- since ubiquitous, single positive result is lab contamination and positive from immunocompetent is not concerning
- banana-shaped macroconida with “foot cell” at base
- hyphae in tissue look like aspergillus, but fusarium will have yeast form
- PCR-based tests and mold metabolism
what is treatment for fusarium?
more innately resistant to antifungals than others
- localized infections: surgical care and topical/oral antifungals (natamycin, voriconazole)
- disseminated: amphotericin B and fast immune reconstitution (poor prognosis)
how to prevent Fusarium?
- high risk patients kept in HEPA-filtered rooms at positive pressure, with filtered water supplies and scrubbed-down showers
- pre-op workup for HSCT must include screening for fusarial infection (may be trivial before immunosuppression)
