MTB, NTM and Fungal Infections Flashcards
How long does it take to culture mTB to visible levels?
3 to 8 weeks on solid media
The term “acid fast bacillus” is practically synonymous for what bacteria?
mTB
What are 3 ways of staining for mTB?
Ziehl-Neelson
Kinyoun
fluorochrome (auramine-rhodamine)
Where is initial primary TB infection localized?
mid lung
What is responsible for the spread of mTB throughout the body?
ingestion by alveolar macrophages, where they carry bacterial to the lymph nodes and through blood
How many weeks after infection is tuberculin positivity seeN/
3 to 8 weeks after
If you have tuberculin positivity, what does that mean from an immune perspective?
cellular immunity and tissue hypersensitivity
Define the Ghon Complex
A marker of TB infection, where antigen concentration in the lung and draining lymp nodes are seen as visible calcification on the CXR
What are epithelioid cells?
they make up granulomas, and are actually stimulated macrophages
What are Langhans giant cells?
fused macrophages surrounding TB antigens - multiple nuclei
A very successful host tissue response
What type of necrosis is typically seen in mTB?
caseating
Define bronchogenic spread in mTB
when caseous necorsis liquefies and discharges, spreading infection throughout the lung
In the first year, what percentage of infected individuals develop active TB?
3 to 4 %
after the first year, what percentage of individuals develop active TB?
5 to 15%
What are the 2 most important determinants of transmission in TB?
close contact
level of infectiousness of the source
What determines source infectivity in TB?
number of TB bacilli
frequency and magnitude of cough
What are typical CXR findings in reactivated TB?
apical infiltrates with cavitation
What is one of the strengths of interferon gamma release assays for mtB diagnosis, compared to the TST?
ESAT-6 and CFP-10 antigens are very specific to mTB, don’t cross react with BCG vaccine or environmental mycobacteria
What is the main drawback of IGRA testing for mTB?
cost
What groups are most at risk for primary active mTB?
young children, elderly and immunosuppressed
Where does primary active TB infection tend to show?
lower or middle lob with hilar or mediastinal lymphadenopathy
Diffuse reticulonodular infiltrates on CXR for someone with mTB are concerning for what?
miliary TB that has spread to extrapulmonary areas
what are 3 kinds of media that can be used to grow mTB?
solid egg based (lowenstein jensen)
solid agar
liquid broth * fastest*
What is the incubation time to detection for growing mTB in liquid broth?
1 to 3 weeks (compared to 3 to 8 weeks)
What is the most sensitive and specific way to detect mTB?
PCR
For latent TB, what is the treatment regimen?
isoniazid x 9 mos
rifampin x 4 months
isoniazid + rifapentine weekly x 3 mos
What is the key drug for treating active mTB?
rifampin - it shortened therapy from 18 mos to 6 mos
What is the standard regimen for susceptible active TB? (remember the catchy little mneumonic)
2 for 4 (2 months of 4 drugs IREZ) or 4 for 2 (4 months of 2 drugs IR)
What is primary v. acquired MDR TB?
primary: patient initially infected with MDR
acquired: poor adherence selects for resistant TB in previously susceptible individual
How is MDR TB defined?
resistant to at least INH and rifampin
how is XDR TB defined?
Resistant to INH and rifampin (MDR) + 3 or more of the 6 second line drugs
What does the BCG vaccine protect against in TB?
fatal TB in children (ie. meningitis)
Does BCG prevent infection with TB?
nope - just the really bad complications, in children, for a limited time that is not extendable by booster shots
How long does the BCG vaccine last?
10 to 20 years
A 24 year-old medical student tests positive on her tuberculin skin test (22 mm of induration). She feels well and denies fever, sweats, cough or weight loss. She reports her tuberculin skin test was negative on entry to medical school 2 years ago. She was born and raised in Vietnam and received the BCG vaccine as a child. Would you recommend any additional evaluation? What is her risk of developing active tuberculosis? Would you recommend treatment?
Yes - BCG is not enough reason to ignore a positive TST.
A confirmatory IGRA would be the next, more specific test that can rule out m Bovis or BCG
If the IGRA is positive, then a CXR and latent TB therapy should be done
A 34 year-old man presents with low-grade fever, sweats, cough and hemoptysis for the past several weeks. He reports a 12-pound weight loss. Empiric treatment with azithromycin provided no benefit. He moved to Chicago from the Philippines 3 years ago and works as an aide at a preschool. A chest x-ray shows bilateral upper lobe cavitary infiltrates. What diagnostic testing do you recommend? Would you start empiric therapy and if so, what? Can he go home and continue his work-up as an outpatient? When can he return to work?
You should send for a sputum AFB smear, mycobacterial culture, and PCR assay for mTB and rifampin susceptibility.
If PCR is not available and your suspicion is high, you can begin empiric therapy for active mTB infection.
You need to hospitalize patients who are very sick or have no stable housing.
If someone is proven to have TB and starts therapy, how long should they wait to resume working etc?
clinical improvement of symptoms plus 3 smear negative sputum samples
What are two common respiratory presentations of NTM pneumonias?
chronic granulomatous pneumonia or bronchiectasis
What are the 3 class of NTM according to the runyon systeM?
rapidly growing
intermediately growing
slowly growing
What is the timeline for rapidly growing NTM?
< 7 days on the plate
What are 3 pathogenic species of rapidly growing NTM?
fortuitum, abscessus, chelonae
What is the timeline for intermediate growing mycobacteria?
7 to 10 days
Which of the intermediate growing mycobacteria grow at lower temperatures?
marinum
Which intermediate growing mycobacteria grow at higher temperatures?
gordonae
which class of mycobacteria (NTM) may need nutritional supplementation to grow?
slowly growing
What are the main pathogenic organisms in slowly growing NTM?
MAC and kansasii
What temperatures do slowly growing mycobacteria grow at?
higher temps (35 to 37)
Chronic bronchopulmonary disease is frequently caused by which NTMs?
MAC
Kansasii
chelonae-abscessus
Disseminated infection is frequently caused by which NTMs?
MAC
Skin abscesses are frequently caused by which NTMs?
marinum
abscessus
fortuitum
What is required for diagnosis of NTM lung disease?
multiple positive respiratory cultures or positive deep respiratory swabs (BAL)
What 2 organisms are the main part of the MAC?
avium and intracellulare
What are the 3 main disease syndromes caused by MAC?
lung disease
disseminated isease
cervical lymphadenitis
How are MAC organisms acquired?
inhalation or ingestion
NOT person to person
Define hot tub lung.
hypersensitivity reaction to MAC (Not invasive infection)
Who are most commonly affected by MAC lung disease?
women in their 50s or 60s, with chronic coughs and fatigue
Define lady windermere’s syndrome
MAC pulmonary infection in tall thin women with chest wall abnormalities and cystic fibrosis tansmembrane conductance regulator mutations
What genetic feature is seen in Lady Windermere’s syndrome
CFTR mutations
How is invasive MAC treated?
multiple agents for 12 to 18 months
What are the most important ABX to include in MAC treatment?
azithromycin and clarithromycin in a 3 - 4 drug regimen
How is m Kansasii acquired?
inhalation from environment, not person to person
how is m kansasii treated? how does it do compared to MAC?
rifampin + other drugs for 18 months (or min. 12 months after negative culture)
typically easier to treat
Funguses such as blastomyces, histoplasma, or coccidioides are normal parts of the human flora, in part because they are so common to our environments, true or false.
False - when found in clinical cultures, they are almost always true pathogens
What are the 3 main presentations of fungal respiratory infection by endemic fungi?
acute pneumonia
chronic pneumonia
disseminated infection
What are 2 opportunistic fungi seen in persons with severe immune defects?
aspergillus and pneumocystis jiroveci
Where is histoplasma found?
river valleys of the Eastern US
What two animals correlate strongly with histoplasma?
bird and bat guano
What is the most comon way that histoplasma is released into the environment, causing infection?
disruption of the soil by excavation or construction
What is the most critical part of establishing infection by histoplasma?
transition from the mycelial to the yeast phase
What is the hallmark tissue response to histoplasma?
caseating or non caseating granuloma
Ghon complex or pulmonary calcifications are seen in which diseases?
histoplasma infection
MTB
What are 2 mediastinal complications of histoplasma infection?
mediastinal lymphadenitis or fibrosis
How is histoplasmosi visualized?
PAS or gomori methanamine
What is a way of rapidly diagnosing histoplasmosis?
serum or urine antigent testing
How is histoplasmosis treated?
amphotericin B and itraconazole
Where is blastomyces endemic to?
Southeastern and south central US (especially great lakes, mississipi and ohio river)
Where is blastomyces found in the environment?
wooded areas
How does pulmonary infection of blasto occur?
inhalation of conidia, which convert to the yeast phase in the warmer lung
What is the typical inflammatory response to blastomyces?
neutrophils and non caseating granulomas with epithelioid and giant cells
What are the most common extrapulmonary lesions found in blastomyces infection?
bone or skin lesions
HOw is blasto diagnosed?
with cytology or histopathology (gomori methenamine silver stain)
Culture
urine antigen
How is blastomyces treated?
amphotericin B and itraconazole
Where is coccidioides found?
southwestern US (four corners, valley fever)
What is unique about coccidioides structure?
they are spherules in the lungs, which convert to endospores
What is a histological sign of mature coccidoides?
alternating mycelial cells with autolysis and true septa
How are cocci infections acquired?
inhaling arthroconidia
How is cocci infection controlled by the body?
T cell immunity
Diabetes or pre existing pulmonary fibrosis can contribute to what complication of cocci infection?
chronic fibrotic pneumonic process with infiltrates and cavitation
Where is cocci most commonly disseminated to?
joints, bones and skin
What is a serious complication of cocci infection?
coccidioidal meningitis
HOw is cocci diagnosed?
by cytology stains, Hand E stains, or silver and acid-schiff stains
Serology is most common
What is an important safety measure to take when diagnosing cocci infection?
Telling lab personnel that cocci is suspected, so that they do not open the culture container and inhale it
How is cocci meningitis diagnosed?
by serology! CSF fungal cultures are frequently negative
HOw is persistent cocci pneumonia treated?
itraconazole
How is cocci meningitis treated?
lifelong fluconazole
How is aspergillus infection acquired?
inhalation of the conidia
What cell type plays an important role in controlling aspergillus infection?
neutrophils
A patient presents with fungal infection that progresses across tissue planes, has vascular invasion and infarct of tissue distal to those vessels. What do they have?
aspergillosis
What is unusual about the presentation of patients with aspergillosis who have severe neutropenia?
absence of fever or localized pulmonary symptoms
What imaging is used to diagnose aspergillus?
CT
CXR is not sensitive
How does pulmonary aspergillosis present on CT?
Pulmonary aspergillosis typically presents as single or multiple nodules with or without cavitation, patchy consolidation or peribronchial infiltrates.
Halo sign is common
What is the halo sign?
A nodule with surrounding ground glass infiltrate reflecting hemorrhage. common with aspergillosis
a patient has a pulmonary infection. On histopathology, they have septate hyphae with acute angle branching. What is it?
aspergillosis
How is aspergillus infection confirmed?
culture of tissue or BAL
What are 3 pathogens that can cause similar diseases to aspergillosis?
mucormycosis
fuasrium
scedosporium
* more for recognition than memorization
How is aspergillosis treated?
voriconazole
What are the 3 morphologic forms of pneumocystis jiroveci?
cysts
sporozoites
trophozoites
at what CD4 count does PJP (pneumocystis jiroveci) pneumonia occur?
with a CD4 count less than 200
What is the typical PJP presentation in HIV patients?
gradual onset
fever, cough, progressive dyspnea
crackles and rhonchi maybe
HOw is PJP diagnosed?
elevated LDH (exudative pleural effusions), hypoxemia, diffuse infiltrates, BDG assay
How is a PJP diagnosis confirmed?
immunofluorescent antibody staining of sputum or BAL fluid
how is PJP treated?
TMP-SMX
What is an additional treatment offered to individuals with severe PJP?
corticosteroids to reduce respiratory failure and inflammation
A 55 year-old female presents with several weeks of malaise, dyspnea on exertion and cough productive of yellow sputum. Chest x-ray and chest CT show patchy ground glass infiltrates and bronchiectasis. Cultures of sputum and from bronchoscopy both show heavy growth Mycobacterium avium complex. An HIV test is negative. Is any further evaluation necessary? Is treatment indicated?
This presentation is consistent with pulmonary MAC infection. The usual treatment regimen is a combination of azithromycin, ethambutol and rifampin for a period of 12-18 months (6 months after repeat sputum cultures are negative for MAC).
A 72 year-old male presents with a history of COPD and chronic cough. He reports a 70 pack year history of tobacco, but quit 2 years ago. CXR shows evidence of emphysema. Sputum culture is positive for moderate growth of Mycobacterium gordonae. An HIV test is negative. Is any further evaluation necessary? Is treatment indicated?
No anti-mycobacterial therapy is indicated based on the available information. M. gordonae is a very unlikely pathogen and the diagnosis of NTM lung infection requires multiple positive sputum culture or a single positive BAL culture. He may benefit from additional treatment for his COPD.
A 44 year-old woman with HIV/AIDS and a long history of poor adherence with antiretroviral therapy presents with fever, sweats, weight loss, abdominal pain and diarrhea. CT scan of the abdomen shows hepatosplenomegaly and enlarged periaortic and mesenteric lymphadenopathy. Cultures of blood and sputum show growth of M. avium complex. Is any further evaluation necessary? Is treatment indicated?
This presentation is characteristic of disseminated MAC infection in the setting of advanced AIDS. Treatment with azithromycin, ethambutol and rifampin is indicated. Patient with advanced HIV/AIDS often defy Occam’s Razor, so although all of these findings may be attributable to disseminated MAC, you should be on the lookout for other opportunistic infections and malignancies if she does not improve with treatment.
A 37 year-old male presents with several days of cough, chest discomfort and low grade fever. He is otherwise healthy. Chest x-ray shows diffuse pulmonary infiltrates. He undergoes bronchoscopy which shows spherules with numerous endospores on cytology. An HIV test is negative. Is any further evaluation necessary? Is treatment indicated?
The presence of spherules and endospores is diagnostic of coccidioidomycosis. The diagnosis should be confirmed by culture. Pending culture results, serology (Coccidioides complement fixation) and urine and/or antigen testing may provide additional support.
A 56 year-old woman with acute myelogenous leukemia undergoes chemotherapy which results in neutropenia (absolute neutrophil count <100). She develops fever and is started on empiric broad spectrum antibacterial therapy. Her fever resolves, and cultures of blood and urine remain negative. Ten days later she remains neutropenic and her fever recurs. She complains of some dry cough and chest pain. Chest CT scan shows a dense nodular infiltrate in the left lung base. Empiric treatment is indicated for what fungal pathogen? Are there any relatively non-invasive tests that might support your suspected diagnosis? How can you confirm the diagnosis?
Empiric treatment is indicated for invasive fungal pneumonia – aspergillosis in particular, but consider also fusariosis and mucormycosis. Appropriate agents include liposomal amphotericin B (Ambisome), or an extended spectrum azoles (voriconazole, posaconazole or isavuconazole). Serum galactomannan antigen and serum beta-d-glucan testing may support the diagnosis of aspergillosis or fusariosis (but not mucormycosis); these tests may also be performed on BAL fluid. Confirmation of the diagnosis requires recovery in culture – typically obtained via bronchoscopy +/- biopsy.
