Opportunistic Fungal & Filamentous Bacterial Infections Flashcards
What 3 filamentous bacteria cause indolent pneumonia in immunocompromised hosts and superficially resemble fungi in their slow clinical course?
Actinomyces
Nocardia
Rhodococcus (less important bc so rare)
What are the 2 most pertinent opportunistic yeasts? Fungi?
Yeasts:
- candida
- cryptococcus
Moulds:
- Aspergillus
- Zygomycetes
___________ is the most common cause of invasive mould infections in transplant and cancer patients..
____________ are classically associated with fungal sinusitis with brain invasion in patients with diabetes.
Aspergillus = most common in cancer/transplant
Zygomycetes = diabetes
Filamentous bacteria, like all bacteria are __________. They grow as thin ____________________ when in the exponential growth phase but revert to __________ single cells when in the plateau phase.
Prokaryotes that grow as thin branching filaments in the exp. growth phase, but revert to coccobacillary single cells in the plateau phase
What are the 3 main morphologies of fungi?
Give examples of each.
Yeast- cryptococcus, candida
Mould- aspergillus, zygomycetes
Dimorphic- histoplasma, blastomyces, coccidiodes
What are the 3 main drug options for fungi?
- Ergosterols- fungal cell membrane are inhibited by polyenes like amphotericin
- Azoles- inhibit fungal p450 14a demethylase that makes ergosterols
- eichinocandins- inhibit 1,3 B glucan synthase so targets cell wall of fungi
How can you differentiate growing bacterial filaments from fungal hyphae?
The fungal hyphae are thicker microscopically
Describe the most common actinomyces strain. Is it aerobic or anaerobic? Gram + or Gram - How does it grow? What differentiates them from nocardia?
Actinomyces israelii
- anaerobic/ aerotolerant
- G+ but stain irregularly
- branching filamentous rods
- different from nocardia because it does NOT have mycolic acid and is NOT weakly acid fast
Where is actinomyces found?
How does it cause disease in immunocompetent hosts?
In the normal oral flora and the female genital tract
- Trauma
- foreign bodies (like IUDs)
- injury/poor dentition
Why is actinomyces often mistaken for malignancy?
The infected tissue contains relatively few organisms and is a slowly growing mass of fibrous and inflammatory tissue that forms sinuses and fistulae
What are the 3 main syndromes associated with actinomyces?
- orocervicaofacial
- pulmonary disease
- abdominal/pelvic infections
____________ infection is the most common presentation of actinomyces. It is the result of _____________ and/or __________________.
Orocervicofacial infection is the result of:
- poor dental hygiene
- invasive dental procedures
A patient comes in to your office with a soft-tissue mass near the mouth that is painless, but shows fibrosis and scarring. He says he was at the dentists office last week getting a root canal.
What is the likely culprit of his infection?
His infection is likely to spread to _______ or _____ that drain from the original site of infection.
What are you likely to find on a stain of this?
Actinomyces- orocervicofacil infection
His infection spreads to sinus tract and fistula and you will see “sulfur granules”
A patient comes in with subacute chronic fever, chills, cough, night sweats and weight loss. You are suspicious of TB, but note that he has terrible dentition and extremely foul halitosis.
What should DEFINITELY be on the differential with TB?
Actinomyces
How does actinomyces appear on CXR.
Can be single lesion or multifocal
A distinguishing feature is that it does NOT respect anatomical boundaries so it can cross the pleura, lobes of the lung, extend through the thoracic wall, etc
A woman comes in complaining of abdominal pain, fever, night sweats and weight loss. When taking her history she tells you that she recently had an IUD put in. What is your #1 suspicion?
What are 2 other things that should be put on the differential?
What is treatment?
Actinomyces causing abdominal/pelvic syndrome
Consider:
Crohn’s
ulcerative colitis
Treatment is surgical resection of the infected tissue and a long course of antibiotics.
What are the 2 critical clues to the diagnosis of actinomyces on histopathological examination?
Is culture useful for diagnosis?
- sulfur granules (large ones are macroscopically visible in draining sinuses)
- masses of branching bacterial filaments surrounded by inflammatory debris
Culture would be diagnostic but it takes a minimum of 2 weeks (but often longer) for it to grow. When it does grow, however, it looks like a MOLAR TOOTH with aerial stalks
What is treatment for actinomyces?
- several weeks of IV PenG
- 6-12 months oral therapy of amoxicillin/clavulanic acid
Clindamycin&moxifloxacin in Pen allergic patients
Describe Nocardia.
- aerobic or anaerobic
- G+ or G-
- how does it grow?
- how is it differentiated from actinomyces?
- where is it typically found?
Aerobic
G+, weakly acid fast
It grows as branching filaments
It is differentiated from actinomyces because it has mycolic acid and stains weakly acid fast.
typically found in soil
What 2 major characteristics are similar between mycobacteria and nocardia?
- mycolic acid in the cell wall (mycobacteria is longer chained)
- trehalose dimycolate cord factor- allows for intracellular growth
How long does it take to grow Nocardia on a non-selective laboratory media?
How do the colonies appear?
It takes 5 days or more to grow
Colonies appear waxy and resemble fungal colonies in that they can form aerial hyphae
Which strain of Nocardia is most often associated with pulmonary disease?
With skin infections in countries in South/Central America?
Pulmonary- N. asteroides
Skin- N. brasiliensis
Where is nocardia usually found?
How do humans get infected?
Who is usually infected?
Where does the organism reside in the host?
It is found in soil and humans acquire it by inhalation.
They typically infect people lacking CMI (corticosteroids, immunosuppression, following transplant)
Nocardia lives within macrophages and prevents phagolysosomal fusion, prevents acidification and avoids killing by respiratory burst
What are the 3 main clinical syndromes associated with Nocardia?
- Sub-acute pneumonia
- Disseminated infection
- Cutaneous disease
A patient presents with cough and dyspnea that has been developing over several months. You treated them for multiple bacterial and fungal infections but they have not improved. What is the likely pathogen and what would you see on CXR?
Nocardia- multiple nodules that may cavitate
In nocardia disseminated infection, what does it typically manifest as?
They typically have pneumonia first and then it spreads to the brain.
- brain abscesses
- chronic meningitis
How is nocardia diagnosed and treated?
What should the lab be careful to do if nocardia is suspected?
Diagnosis:
1. direct examination of sputum, pus
2. biopsy material
(should see weakly acid-fast branching rods. MAY contain sulfur granules)
Hold the cultures for several weeks because sometimes growth can be very delayed.
Treatment:
- Sulfonamides- BACTRIM (trimethoprim-sulfamethazole) for 6-12 months
- decreased degree of immunosuppression
What is the most common fungi that causes human disease?
Describe what type of fungi it is and describe size/structure.
Candida- oval single-celled yeast
3-5 microns in diameter
How does Candida reproduce?
Usually budding, but sometimes they are found as elongated pseudohyphae because the daughter cells fail to separate completely
What are the 4 species of Candida isolates in medical practice?
Why is it important to differentiate them?
How are they differentiated?
C. albicans (most common)
C. glabrata
C. tropicalis
C. parapsilosis
They have different antifungal susceptibilities
- C albicans forms yeast tubes after 90 minutes in culture media while the others do not
- Biochemical tests separate the other strains
Where is Candida typically found?
Commensal in the GI tract and female genital tract
What are the 3 ways Candida causes infection?
- overgrowth in normally colonized surfaces (GI, FGU)
- introduction into sterile spaces (usually iatrogenic)
- hematogenous spread
What are the 4 most common syndromes associated with Candida?
Which can occur in immunocompetent patients?
- Oral thrush- white plaques that can scrape off
- vaginal thrush- discharge, dyspareunia, itching, inflamed with white exudate
- infections of moist macerated skin (like diaper rash)
- esophagitis- dysphagia, chest pain
1,2,3 all can occur in immunocompetent
What is the cause of candidal infection of deep tissue?
Iatrogenic:
- IV lines
- post-op peritonitis
- UTI from bladder catheter
Remove the device, treat the infection, reimplant if necessary
Hematogenous spread of candida occurs under what two situations?
What are the 4 main things candida does when it spreads?
- spread from deep infections- IV line sepsis
- NEUTROPENIA (chemo)
Spread goes to:
- Eyes- edopthalmitis
- septic emboli to lungs/brain
- skin
- hepatosplenic candidiasis (neutropenic)
What typically precedes a candida infection?
Anti-bacterial therapy because it disrupts the normal flora and allows for the growth of candida
How is candida diagnosed for:
- oral and vaginal candidiasis
- deep infections
Diagnosis oral and vaginal :
- appearance alone
- wet smear confirms diagnosis
Diagnosis of deep infection:
1. isolation of organism on blood or other sterile sample culture
What is treatment for oral or vaginal Candida?
Esophageal candida?
Oral and vaginal:
Topical antifungals (nystatin, clotrimazle, miconazole)
Vaginal alone:
**fluconazole - more effective, more expensive
Esophageal:
Systemic fluconazole
EICHINOCANDINS AND AMPHOTERICIN ARE RESERVED FOR RESISTANT STRAINS
For invasive candida infections, what is treatment for non-neutropenic patients?
Neutropenic patients?
Why is treatment different?
Normal -fluconazole
Neutropenic- amphotericin B and/or eichinocandin
Azoles are fungistatic and require functioning neutrophils to help kill the fungus.
Crypto neoformanns is an encapsulated yeast that grows where?
What are the 2 main types?
Grows in soil rich in bird poop.
Neoformans - A, D, AD - bird poop
Gatti- B C - eucalyptus trees
Describe the structure, size and distinguishing properties of cryptococcus neoformans.
It is a unicellular encapsulated yeast.
It is a 2-20micron sphere (much larger than candida which is only 1-5)
The capsule is refractory polysaccharide that reproduces by budding (not pseudohyphae like candida)
What staining is done on cryptococcus? Why?
India ink to visualize the capsule
How do humans get cryptococcus?
What disease does it cause?
People acquire it by inhalation.
In immunocompetent, it is confined to the lungs.
HIV with CD4 <100 it presents as subacute chronic menigitis.
What is the major virulence factor of cryptococcus?
What are its 2 major functions?
What other virulence factor does cryptococcus have?
MAJOR VIRULENCE FACTOR
the surface polysaccharide capsule is the virulence factor. (Unencapsulated variants are avirulent).
1. antiphagocytic
2. survives in inactivated macrophages- this prevents CMI from activating macrophages to promote killing.
MINOR VIRULENCE FACTOR
-the production of melanin
What are the 2 major clinical syndromes associated with cryptococcal disease?
- pulmonary
- asymptomatic
- mild lobar pneumonia
- COIN LESION.
- NO cavitation - disseminated
- meningitis (HIV) with gradual headache, fever, neck stiffness, confusion
- skin nodules with central umbilication
How do we diagnose cryptococcus?
Most common and most diagnostic:
serological assay to detect polysaccharide antigen
- grows readily in blood culture
- Gram stain and India Ink can give PRESUMPTIVE diagnosis
What is treatment for cryptococcal meningitis?
What is treatment for mild to moderate cryptococcal disease?
- Amphptericin B in combo with 5-fluorocytosine for meningitis
- fluconazole for mild/moderate disease
What type of fungi (yeast,mold,dimorphic) is Aspergillus?
Where is is niche?
It is a filamentous mould that is ubiquitous and unavoidable in the environment (although it favors decaying organic material/soil).
Conidia are small, produced in large number and easily airborne
Most human diseases caused by Aspergillus species involve the _____________ or the _____________________.
Respiratory tract or paranasal sinuses
What are the 4 main species of aspergillus and what is the most common?
Which one needs to be treated differently?
- fumigatus- most common (gray)
- flavus (yellow)
- niger (black)
- terreus (brown) - is intrinsically resistant to amphotericin because it uses sterol instead of ergosterol
What are the 3 main clinical syndromes of aspergillus?
- colonization of mucousal surfaces without tissue invasion
- invasive infection
- hypersensitivity disease- exuberant response of the host to the organism without tissue invasion
Aspergillus colonization of the respiratory tract is usually ____________ but is relatively common in patients with__________________.
usually asymptomatic but is relatively common in patients with underlying respiratory diseases like:
- COPD
- bronchiectasis
- CF
How does one usually discover the colonization of aspergillus?
growth in a routine culture of sputum
Which bacteria grows out TB and other lung cavities? What is the result?
Aspergillus- this causes a visible ball of mould that can be seen on CXR. It is called:
- aspergilloma
- fungus ball
- pulmonary mycetoma
What is the hypersensitivity disease associated with Aspergillus?
Allergic Bronchopulmonary Aspergillus (ABPA) -
Inhaled spores are the allergen which causes an exuberant Th2 response .
Hyphae–> Th2 response–>inflammation–> scarring–> bronchiectasis–> permanent lung damage
What is the most common and most severe disease caused by aspergillus? Who does it occur exclusively in?
What is the prognosis?
Invasive aspergillosis
-immunocompromised patients (neutropenia)
50-90% case-fatality even with appropriate therapy
Describe the pathogenesis and host factors of aspergillus that contribute to invasive disease.
- Inhale conidia–> not killed by neutrophils in neutropenic patient–> convert to hyphae
- Hyphae grow filamentously within tissue
- hyphae are angioinvasive and get into bloodstream
- Thrombosis and vessel ischemia–> INFARCTION
The most widely recongized risk factor for invasive aspergillosis is ______________.
It is much less common in patients with ________ and on ________.
prolonged and severe neutropenia
- acute leukemias
- cytotoxic chemotherapy
- transplant patients
late stage AIDs and on corticosteroids because this only affects CMI and the conidia of aspergillus are killed by neutrophils
How do you make definitive diagnosis of Aspergillus?
- Histologic evidence of tissue invasion with hyphae elements: thin septal hyphae with acute branching (45degrees)
- culture
- ELISA for galactamannan
What is treatment of aspergillus?
When should it be initiated?
Do NOT wait getting a definitive diagnosis to treat. Recovery of neutrophils is the most important function.
- voriconazole - prophylaxis and treatment
- amphotericin B
Describe how zygomycoses grow in culture?
Describe the structure.
Long-stalk with bulbous swelling on the end that contains conidia
- broad and ribbon-like, NON-SEPTATE
- hyphae are 2x as wide as aspergillus
- BRB (broad root base)
Where are zygomycoses found? How do people acquire them?
They are ubiquitous in soil with dead/dying vegetation.
People acquire conidia via inhalation
Who is most at risk for infection by zygomycoses induced rhinocerebral mucormycosis?
What does this disease do?
- Diabetics with ketoacidosis -
destructive fungal invasion of the nose, palate, sinuses and into the brain
(less commonly: high dose steroids, bone marrow transplants)
You are performing a physical exam and notice black, necrotic areas of the nasal mucosa and hard palate. The patient had fever, sinus pain, discharge,
They have started developing diplopia and neuro deficits.
What is the likely cause?
Zygomycosis
How is diagnosis made for zygomycoses?
Biopsy-
broad based non-septate hyphae branching at 90 degrees is consistent with zygomycosis
*need culture to identify species by looking at differing fruiting bodies
What is treatment for invasive rhinosinusitis or invasive pneumonia caused by zygomycoses?
- Surgical resection
- amphotericin B
- Posaconazole for salvage therapy
