SM 178a - MTB, NTM, Fungal Flashcards
What is the clinical presentation of pneumocystis pneumonia?
- Progressive, exertional dyspnea
- Fever
- Nonproductive cough
- Chest discomfort
- Worsens over days-weeks
Which fungal pneumonias are typically seein in patients with impaired immune systems?
Aspergillosis
Pneumocystosis
Coccidioides exist as _______ in the environment and ______ in tissue
Coccidioides exist as mycelia** in the environment and **spherule in tissue
Which NTM is most likely to cause a pulmonary infection similar to pulmonary tuberculosis?
M. Kansasii
Where is MAC found?
Environemntal sites: Water, soil, animals
Infection is likely acquired by inhalation or ingestion
No person to person spread
Which fungus is this?
- Histoplasma capsulatum*
- Large, rounded, single-celled tuberculate macroconidia w/smaller microconidia
What will you see in a biopsy of somebody infected with NTM?
Possible granuloma
Possible AFB
Describe the clinical presentation of tuberculosis
- Fever
- Night sweats
- Weight loss
- Shortness of breath
- Hemoptysis
- Cough >2 weeks
- History of exposure to infectious TB or positive TST
What is the standard treatment for latent TB infection?
One of the following
- Isoniazid daily for 9 months
- Rifampin daily for 4 months
- Isoniazid + Rifapentine 1x weekly for 3 months
Which x-ray shows primary tuberculosis?
Which one shows reactivation tuberculosis?
- Left = primary
- In the middle lobe
- Right = reactivation
- In the apical, posterior upper lobe
- Granulomas/cavitations
What are the advantages of the Xpert MTB/RIF test?
- Test for tuberculosis presence and antibiotic resistance at the same time
- Can get results on the same day
- Reduces the median time to treatment
Which fungal organism is this?
Blastomyces dermatitidis
A 63 yo woman presents with chronic cough, weight loss and bronchiectasis on chest CT scan. Which of the following supports the diagnosis of nontuberculous mycobacterial infection?
- Household contact with active NTM infection
- Positive tuberculin skin test
- Isolation of Mycobacterium avium complex from 1 of 3 sputum specimens
- Isolation of Mycobacterium gordonae from BAL
- Isolation of Mycobacterium abscessus from BAL
e. Isolation of Mycobacterium abscessus from BAL
What is the treatment for mycobacterium kansasii?
Guided by susceptibility testing
Isoniazid + rifampin + ethambutol for 18 months
(>12 months after respiratory cultures are negative)
Describe the clinical presentation of coccidioidomycosis
Possible presentations
- Asymptomatic/subclinical
- Nonspecific respiratory infection
- Pulmonary nodule
- Chronic fibrotic pneumonia
- Disseminated disease
Which fungal organism is this?
Aspergillus
What stain would you use to visualize MTB?
Acid-fast bacillus stain
- Ziehl-Neelsen stain
- Kinyoun stain
- Fluorochrome stain
What are the limitations of the PPD skin test (TST)?
- Requires follow-up
- Operator error in application and interpretation
- Cross-reactions with BCG and MAI
- Negative in 25% of people with active disease
Describe the clinical presentation of blastomycosis
- Pulmonary blastomycosis
- Acute or chronic
- Mimics other pulmonary infections
- Pyogenic bacteria, tuberculosis, other fungal, malignancy
- Extrapulmonary manifestations
- Cutaneous disease
- Bone infection
How are endemic mycoses infections acquired?
Inhalation of the environmental hyphal form
No evidence of transmission among humans and animals
Endemic mycoses = histoplasmosis, blastomycosis, coccidioidomycosis
Which fungal organism is this?
Blastomycosis dermatitides
Broad based budding yeast
Which species of pneumocystis infects humans?
P. jiroveci
How is aspergillosis treated?
Voriconazole
Recovery of neutrophils in patients w/neutropenia is critical
Name some of the slowly growing mycobacteria (>7 days)
MAC, kan you grow any faster??
- MAC
- M. avium and M. intracellulare
- M. kansasii
Describe the presentation of a Mycobacterium kansasii infection
Pulmonary infection that mimics pulmonary TB
How is aspergillosis diagnosed?
Definitive diagnosis requires recovery of aspergillus in culture of tissue or BAL fluid
- Septate hyphae with acute angle branching
In a person with a concurrent HIV infection, where is latent tuberculosis most likely to reactivate?
Middle lobe of the right lung
Who is at highest risk for progressive primary tuberculosis?
Young children
Elderly people
People with advanced HIV/AIDS
Which NTM is not real, according to Dr. Flaherty?
M. gordonae
Who is at high risk for aspergillosis?
People with prolonged, profound neutropenia
Which fungal organism is this?
Coccidioides immitus
Spherules in the lungs
Which fungus is most likely to cause an infection that crosses tissue planes and invades blood vessels?
Aspergillus
Name some of the intermediately growing mycobacteria (7-10 days)
MG = medium growth
- M. marinum
- M. gordonae
What is the typical inflammatory response in blastomycosis?
Clusters of neurtophils and noncaseating granulomas with epithelioid and giant cells
Which cells contribute to tissue hypersensitivity associated with a TB immune response?
Lymphocytes
Which form of coccidioides is inhaled, causing infection?
Arthroconidia
What qualifies as XDR TB?
Resistance to Isoniazid and Rifampin
AND
Resistance to any fluoroquinolone
AND
Resistance to any one of the second-line anti-TB injectable drugs
Which tuberculosis patients are likely to have hilar adenopathy?
Patients with primary tuberculosis
(Patients with reactivation tuberculosis will not have hilar adenopathy)
Describe the presentation of M. chimaera infection
- Endocarditis
- Vascular graft infections
- Surgical site infections
- Disseminated infection following cardiac surgery
50% mortality despite treatment
Associated with contaminated heater-cooler devices
How is blastomycosis acquired?
Inhilation of conidia of B**lastomyces dermatitides
Converts to yeast phase in the lung
How are endemic fungal infections acquired?
- Aspiration of oropharyngeal colonization
- Inhalation of droplet nuclei generated by the cough of persons with cavitary pulmonary infection
- Inhalation of infectious conidia
- Hematogenous spread from sites of cutaneous inoculation
c. Inhalation of infectious conidia
Where in the lung is primary tuberculosis most likely to occur?
Middle lobe of the right lung
You may also see hilar or mediastinal adenopathy
Can a person with latent TB spread the infection?
No
How is mycobacterium kansasii infection acquired?
From the environment
(no person-person transmission)
What is the characteristic tissue response to histoplasma capsulatum?
Caseating or noncaseating granulomas
Describe the pathogenesis of TB
- Inhalation of airborne droplet nuclei
- Initially, it is focused subpleurally in the midlung zone
- Primary TB infection usuallly occurs in the midlung zone
- It is then ingested by alveolar macrophages, which carry it to regional lymph nodes
- The bacteria can then spread hematogenously
- -> lymph nodes, kidneys, epiphyses of long bones, vertebral bodies, meninges, apical posterior areas of the lung
- Reactivtion TB infection usually occurs in the apical posterior areas of the lung
What is the standard regimen for active TB therapy?
- 2 months of quad therapy (RIPE)
- Rifampin
- Isoniazid
- Pyrazinamide
- Ethambutol
- Follow with 4 months of RI
- Rifampin
- Isoniazid
DOT therapy is recommended
Treatment should continue until sputum cultures are negative for at least 4 months
What are the radiographic findings of pneumocystis pneumonia?
- CXR: diffuse bilateral symmetrical interstitial infiltrates
- Chest CT: patchy ground glass attenuation
Which fungal organism is this?
Aspergillus
Which 3 major disease syndromes are caused by mycobacterium avium complex (MAC)?
- Pulmonary disease
- Disseminated disease
- More common in people with advanced HIV/AIDS
- Cervical lymphadenitis
What kind of tuberculosis is shown in this picture?
Miliary tuberculosis
It is everywhere
What cells are likely to be found near the granulomas associated with TB?
Macrophages and T-cells
The macrophages may have progressed to foam cells
How is blastomycosis diagnosed?
Definitive diagnosis requires recovery in culture
How is coccidioidomycosis treated?
Most infections resolve without treatment
Treat only if serious/symptomatic with amphotericin B, fluconazole, or itraconazole
What defines a latent TB infection?
The presence of M. tuberculosis infection without symptoms or evidence of TB disease
How is histoplasmosis diagnosed?
Culture
Sputum culture (but may not have organisms)
Polysaccharide antigen detection in urine, serum, or BAL
A 57 year-old male presents with fever, cough and a dense infiltrate on CXR; BAL cytology shows broad-based budding yeast.
Where did he likely acquire this infection?
- Ohio and Mississippi River Valley region of the U.S.
- North Central Great Lakes region of the U.S.
- Southwest U.S.
- Martha’s vineyard
- Southeast Asia
b. North Central Great Lakes region of the U.S.
How long after infection does it take for tissue hypersensitivity to develop?
3-9 weeks after infection
In which regions is coccidioidomycosis endemic?
Southwest USA, Mexico
What is the source of NTM infection?
The environment (not other humans)
What is Pott’s disease?
Tuberculosis spondylitis
(Tuberculosis infection of the spine)
Name some of the rapidly growing mycobacteria (<7 days)
FAC = fast!
- M. fortuitum
- M. abscessus
- M. chelonae
Which NTm is likely to cause pulmonary disease, cervical lymphadenitis, or disseminated disease (in non-immunocompetent patients)?
Mycobacterium avium complex (MAC)
MAC = M. avium and Mycobacterium intracellulare
In a previously healthy person, where in the lung is latent tuberculosis most likely to reactivate?
Apical posterior portion of the lung
No hilar adenopathy
What is the primary reservoir of ongoing tuberculosis transmission?
A. Unrecognized spread from individuals with latent tuberculosis
B. Untreated active pulmonary tuberculosis
C. Unpasteurized cow’s milk
D. Untreated drinking water
B. Untreated active pulmonary tuberculosis
Endemic mycoses exist in their __________ form in the environment and their __________ form in tissue
Endemic mycoses exist in their hyphal** form in the environment and their **yeast form in tissue
Endemic mycoses = histoplasmosis, blastomycosis, coccidioidomycosis
Do non-tuberculosis mycobacteria (NTM) cause latent infections?
No
Which fungi can cause pneumonia in immune-competent people?
(Endemic fungal pneumonia)
Histoplasmosis
Blastomycosis
Coccidiodiomycosis
How is blastomycosis treated?
- Immunocompetent host
- Asymptomatic disease is limited to the lungs in an immunocompetent host - no treatment
- Asymptomatic disease is limited to the lungs in an immunocompetent host - no treatment
- Immunocompromised host
- Progressive or extrapulmonary disease:
- Amphotericin B, Itraconazole
Which media would you use to grow MTB?
Lowenstein-Jensen, but it takes a long time
Middlebrook liquid broth is faster
This liver biopsy shows mycobacterium avium complex infection.
What else is most likely true of this patient?
They are not immunocompetent
There are so many MACs in the biopsy - you would only see this many in a severely immunosuppressed patient
If you see granulomas but no tuberculosis bacteria, can you rule out TB infection?
No!
You won’t always see the organisms because sometimes there are only a couple hundred in the whole body
What NTM is likely to cause endocarditis, vascular graft infections, surgical site infections, or disseminated infection following cardiac surgery?
M. chimaera
Which fungal organism is this?
Coccidioides immitus
Arthroconidia form
What is the natural course of untreated TB disease?
3 years until self-cure or death
Case fatality = 50%
(Higher in people who are HIV positive)
Where is Histoplasma capsulatum most commonly found?
In the soil of river valleys
In the US: think south of Illinois
How is histoplasmosis treated?
No treatment unless symptoms have lasted > 4 weeks
- Acute pulmonary disease w/symptoms > 4 weeks
- Itraconazole 6-12 wks
- Chronic pulmonary disease, disseminated disease, granulomatous mediastinitis
- Amphtericin B then Itraconazole 6-24 mo
What is the treament for Pneumocystis pneumonia?
- Trimethoprim-sulfamethoxazole
- Corticosteroids (severe disease)
What is the treatment for MAC?
Guide with susceptibility testing
Standard:
Clarithromycin or azithromycin
+
rifampin or rifabutin
+
ethambutol
for 12-18 months
+/- streptomycin for 2-3 months
What are the clinical manifestations of histoplasmosis?
Asymptomatic or mild flu-like illness
Gohn complex and pulmonary complications are common in healed pulmonary histoplasmosis
Can cause respiratory complications
What is the mycobacterium avium complex?
Two closely related organisms
M. avium and M. intracellulare
What qualifies as MDR TB?
Resistance to Isoniazid and Rifampin
How is coccidioidomycosis diagnosed?
- Spherules visualized by cytology stains and in tissue
- Growth on media after 5-7 days
-
Serologic testing - most frequent
- Specific for active infection
- Urine or serum antigens
Why is MTB poorly antigenic?
Lots of high-molecular-weight lipids in the cell walls allow MTB to “hide” from our immune system
What are the morphologic forms of pneumocystis?
Which one is transmissible?
-
Cysts
- Transmissible form
- Sporozoites
- Found within cysts – a mature cyst may contain up to 8 sporozoites
- Trophozoites
- Free-floating form which resemble platelets and tend to cluster
What are the findings of aspergillosis on chest CT?
- Single or multiple noduels, +/- cavitation
- Patchy cosolidation or peribronchial infiltrates
- Halo sign
- Nodule with surrounding ground glass infiltrate
Definitive diagnosis requires recovery of aspergillus in culture of tissue or BAL fluid
What is the major vaccine against TB? Is it effective?
BCG vaccine
Effective for a limited period of time in children at preventing systemic TB, but it has little efficacy against respiratory TB
What kind of immunity is most important in fighting TB?
Cell-mediated immunity (lymphocytes)
Which fungal organism is this?
Coccidioides immitus
Arthroconidia form
What would you see in the CSF if a patient is infected with tuberculous meningitis?
- Lymphocytic or mixed pleocytosis
- High protein
- Low glucose (sometimes later in the course)
- Negative cultures
What is a Langhans giant cell?
Fused macrophages oriented around tuberculosis antigens
Multiple nuclei can be seen peripherally
If you see this finding on a chest CT in a patient respiratory symptoms and a neutrophil count of 65 /uL, what is your leading diagnosis
This is a halo sign, characteristic of aspergillosis
Usually not seen in healthy people - especially common in patients with neutropenia (<100 ug/L)
Where is Blastomyces dermatitis found?
Warm, moist soil of wooded areas righ in organic debris
In the US: Think North of Illinois
How is NTM infection diagnosed?
- Multiple positive respiratory cultures
- BAL - only requires one positive sample
Recovery of NTM in a single sputum sample is not proof of an NTM disease - they might just be hanging out there
How doe people become infected with NTM?
Who is at risk?
NTM exist everywhere in our environment
- People who are immunosuppressed are at particular risk for NTM infection
- Prevalence is increasing in immune-competent peole
- Ex: accidental injection into skin
