ID Flashcards
Neutropenic patient with hemoptysis?
Think about aspergillus, which is the most common cause of hemoptysis in neutropenic patients
Clinical subtypes of invasive aspergillus?
Pulmonary
Rhinosinusitis - can get necrotic areas, epistaxis, facial pain
Tracheobronchitis - obstructive plugs, ulceration, pseudomembranes
Disseminated
Describe the schematic breakdown for aspergillus complications
See evernote on aspergillus in ID section
Risk factors for invasive pulmonary aspergillosis?
- Prolonged neutropenia (<500 for >10 days)
- Transplantation - in particular lung transplant and HSCT
- > 3 weeks (prolonged) high dose corticosteroid therapy
- Hematological malignancy
- chemotherapy
- Advanced AIDs
- CGD
Treatment for invasive pulmonary aspergillosis
Voriconazole
Causes of false negative TST?
Non-technical: Infections: - Bacteria: active TB, pertussis - Viral: HIV, VZV - Fungal (blastomycoses) - live virus (measles, mumps, polio, varicella) - Chronic kidney disease - lymphoma - Drugs - corticosteroids, TNF alpha inhibitor - Age - newborn, elderly patients - Stress--surgery, burn, mental illness
Technical:
- Related to tuberculin: improper storage, improper dilution, chemical denaturation, contamintion
- Method of administration: too little antigen, subcutaneous injection
- Factors related to reading: inexperienced reader
Causes of false positive TST?
- Other mycobacterial infection
- BCG vaccination
- Allergic reaction
For TST of 0-4 mm, in which group is this defined as positive?
Less than 5 years of age AND high risk for TB infection (Because of exposure)
For TST of 5-9 mm, in which group is this defined as positive?
- In many of the groups where there is risk of false negative, we have a lower cut off for defining positive test
- Immunodeficiency:
- HIV and well
- Corticosteroids (>=15 mg/day x >=1 month)
- TNF alpha inhibitor
- Organ transplant
- Close contact of active contagious disease in the last 2 years
- End stage renal diseaes
- Fibronodular disease on CXR (healed TB)
What is the typical cut off for defining a positive TST?
> = 10 mm
Categories:
0-4 mm
5-9 mm
>=10 mm
If you find a non-tuberculous mycobacterium on a sputum or BAL for a patient, then is that bacteria the cause of the patient’s respiratory symptoms?
- It very likely is NOT the cause of the patient’s respiratory symptoms.
- Thought of as an opportunistic bacteria with low pathogenic potential, so it’s not enough to just identify NTM and label it as the cause of disease
- Challenges with labelling NTM disease just based on positive sample:
- Environmental contamination
- Transient recovery
- Colonizer
- Or could be truly pathogenic
Treatment of PJP?
septra 15-20 mg/kg/day IV or po in 3-4 divided doses x 3 weeks (high dose IV septra x 21 days, but can finish with oral if patient is improving)
If PJP + moderate to severe hypoxemia (PaO2<70 on room air), then glucocorticoids
Imaging findings of invasive pulmonary aspergillosis?
CXR: peipheral lung nodules
CT: halo sign, air crescent (necrosis within lung nodule)
If suspecting fungal pulmonary infection, what cell wall antigens can be tested for?
- Galactomannan –>released by growing aspergillus
- Beta-D glucan
How is TB infection defined?
How do you differentiate the types of TB infection–>latent TB versus TB disease?
- TB infection = positive TST
- Symptoms and radiographic findings on CXR are the key things that differentiate latent TB versus disease
- It’s no sputum culture which make that differentation
- TB disease: symptoms or signs or radiographic manifestations + positive TST
- Latent TB: positive TST, but no symptoms or signs or radiographic features
Child >=5 years of age with exposure to TB. What is the management?
- Evaluate as soon as possible with physical exam, CXR, TST or IGRA
- If TST/IGRA is negative, then repeat at 8-12 weeks since the initial test could have been a false negative with early TB infection
- Unlike for children <5 years, there is no need for a window of prophylaxis
Child <5 years of age with exposure to TB. What is the management?
- Evaluate as soon as possible with physical exam, CXR, TST or IGRA
- If there is no evidence of TB infection, then give a window of prophylaxis with INH
- Repeat TST/IGRA in 8-12 weeks. If the repeat test is negative and no concern about this results, then the window of prophylaxis could be stopped. If you are concerned that it’s a false negative (Eg. age, malnutrition, immunocompromised), then complete a course of treatment for latent TB (if there is no evidence of TB disease)
Who should be tested for latent TB?
(We don’t indiscriminantly test everyone for latent TB. Testing for latent TB is based on the risk factors for progressing to TB disease). Latent TB matters if there is a high risk for developing active TB
- Recent infection, within the last 2 years
- Organ transplant
- HIV
- Immunosuppressive medication - TNF alpha, prolonged steroids
- primary immunodeficiency
- malignancy
- malnutrition
- Age:
- <2 years
- Adolescence
(in the absence of risk factors, the risk of progressing from latent TB to active TB is 5-10%)
How do we treat for latent TB?
- In a child >=2 years of age: rifampin x 4 months (better adherence compared to other treatment regimens).
- I would assume that for a child <2 years of age–>INH x 9 months
How does active TB usually develop?
- It’s usually due to reactivation of latent TB
What are the investigations for a patient with suspected active TB?
- CXR
- 3 gastric aspirates or sputum sample: smear, AFB culture, drug susceptibility testing
- HIV
- Xpert MTB/RIF–>can test for rifampin resistance
Advantage of IGRA over TST?
- Doesn’t cross react with most non-tuberculous mycobacteria
- Doesn’t cross react with BCG
- Doesn’t require follow up in 48-72 hours
How do you practically decide between TST or IGRA?
- Kendig’s has a nice alogirthm
- For a child <5 years of age, the preferred test is TST. But if don’t believe results of TST (Eg. TST is negative but you are very suspicious or TST is positive but you think it’s a falsepositive), then do IGRA
- So TST and IGRA can both be used if needed
- For a child >=5 years of age: if they have had BCG, then the preferred test is IGRA. If they will not return for follow up, then preferred test is IGRA. Otherwise, the preferred test is TST.
- If you don’t believe results of TST, then do IGRA
- IGRA is either reported as positive, negative or indeterminate
(uptodate recommends not using IGRA in <2 years of age)
How is TB treated?
- Empiric treatment: INH, rifampin, ethambutol, PZA = RIPE x 2 months, then RI x 4 months (this is while you are waiting to figure out suspcetibility profile).
- If you figure that the TB is fully susceptible, then you can get rid of ethambutol
Treatment Modification after knowing susceptibility profile:
- Fully Susceptible, intrathoracic TB: RIP (rifampin, INH, PZA) x 2 months (initiation phase), then 4 months RI (continuation phase) for minimum total duration of 6 months (It’s handy that ethambutol is not part fo the empiric treatment, since it can be harder to monitor visual symptoms in children)
o Treat for 9 months if cavities on CXR or positive sputum culture after 2 months of treatment
What are side effects associated with TB treatment?
Rifampin: orange discoloration of secretions, hepatitis, drug interactions (especially with drugs metabolized by liver, so can’t take rifampin with ivacaftor containing CFTR modulators), rash (hypersensitivity reaction).
INH: peripheral neuropathy (so need to take pyridoxine = B6)
P: hepatoxicitiy, arthralgia. “Most common cause of drug induced hepatoxicity and rash” (The “a” in the word is for arthralgia)
E: ethambutaol = eyes (optic neuritis), advise patients to report any changes in vision immediately. There should be monthly nursing assessment of vision. If patients are on ethambutol for more than the initial phase, then they should have periodic check ups with opthalmologist. Ethambutol should be used with caution in children, who are too young for monitoring.
(If you can’t think of a drug side effect, then say hepatotoxicity or rash)
- Apart from asking about side effects and periodic visual assessments, there’s no other particular monitoring of side effects, no routine monitoring of liver enzymes (only if pre-existing liver disease or other hepato-toxic drugs)
TB disease versus infection?
TB disease = active TB
Infection could be latent TB or active TB
Fully susceptible intrathoracic TB is treated for 6 months. When would you decide for a longer duration of treatment?
- patients with cavities on initial chest x-ray or cavities on CXR within first 2 months of therapy (then treat for total of 9 months minimum)
- positive sputum cultures after 2 months of treatment = culture positive after 2 months (the minimum duration of therapy should be 9 months)
- Discontinuing RMP or PZA due to side effects. (Rifampin is considered a cornerstone of TB therapy and should not be stopped for minor side effects)
- Having cavity on CXR at the end of therapy (extend total treatment duration to 9 months)
Extrapulmonary TB such as CNS, Disseminated/miliary, bone and joint:
- Treatment duration of 9-12 months
Pulmonary TB in patients with HIV:
- optimal treatment duration is not known
What are the features to consider when deciding if a patient with active TB is infectious?
- Sputum status: smear positive, culture positive
- symptomatic
- treatment for <2 weeks
- if treatment for >2 weeks with no evidence of treatment response (eg. no clinical improvement, no sputum conversion from smear positive to smear negative)
-multi-drug resistant TB and not receiving adequate treatment
(this assessment of infectiousness does not impact the approach to dealing with an exposed individual)
What is the treatment of latent TB?
- rifampin x 4 months, as per 2018 NEJM article, which specifically studies children 0-18 years ofa ge
- for a child <2 years of age–>I might be a bit more conservative and go with INH x 9 months (I think uptodate mentioned this), but I think either option is fine as long as source is mentioned
When a child is the first identified case of TB, what is important to remember in terms of finding the original case?
- Kids usually get infected by adults
After inhalation of TB bacilli, how does primary infection progress in children?
- Either form a caseating granuloma
OR - Primary complex = primary focus, local tuberculous lymphangitis, enlarged lymph nodes
What are the manifestations of intrathoracic TB and how is this different adults?
- Most TB disease in children is from the primary infection, as opposed to from reactivation, which is more common in adults (and more common if primary infection is after puberty)
- Isolated lymphadenopathy (most of these kids are relatively well)
- Progressive primary infection–>looks like an airspace infiltrate on CXR. Can rupture into airway–>endobronchial disease or into pleura–>pneumothorax
- Bronchial disease–>airway narrowing, distal hyperinflation, atelectasis, secondary pneumonia
- Complicated lymph node disease (various consequences of lymph node obstruction)
- Acute pneumonia
Where does reactivation TB tend to happen?
- Posterior segment of upper lobes > superior segement lower lobes due to higher oxygen tension
(The primary infection such as with development with Ghon complex equally affects all regions of the lung, since the primary infection is from inhaling bacilli, as opposed to hematogeneous spread)
What are the features of a ghon/primary complex?
primary focus, local tuberculous lymphangitis, enlarged lymph nodes
Radiographic features of TB disease?
Primary disease:
- Can be seen in any lung zone. (This is the more common subtype in children. Therefore I would not use lung zone as a way to discriminate likelihood of TB).
- Lymphadenopathy
- Infiltrate, which could be lobar infiltrate
- Calcified lesion where granuloma or Ghon complex formed (tuberculoma)
- Can have cavitation, though this less likely than with reactivation TB
- calcified lymph nodes
- pleural effusion
- hyperinflation or atelectasis from airway disease
Reactivation:
- cavitation
- patchy consolidation
- location
- posterior segments of the upper lobes
- superior segments of the lower lobes
- posterior segments of the upper lobes
Radiographic features of latent TB?
- Most patients with latent TB have NORMAL CXR
Radiographs demonstrating stable upper lobe fibro-nodular disease or calcified granulomas are considered to demonstrate evidence of previous active TB and indicate the patient is at increased risk of reactivation–>it may be hard to make this differentiate that a particular lesion is stable, would need sputum cultures to help differentiate
