Tuberculosis Flashcards
What kind of bacteria is Mycobacterium tuberculosis?
Obligate aerobic, slow growing, acid fast bacilli
Why is it challenging to diagnose Mycobacterium tuberculosis under a microscope?
It has a thick waxy cell membrane, therefore it does not produce a typical gram stain response
It is slow growing
Requires acid fast staining for visualisation
Describe the pathophysiology of tuberculosis
M tuberculosis spreads via airborne respiratory droplets. Most of the time, the TB that accesses the lower airways are consumed by macrophages. However, some is able to replicate in the lungs, which then activates our cellular immunity.
What is the difference between latent and active TB?
Latent - cellular immunity takes control of TB replication and therefore patients do not develop any active symptoms
Active - in immunocompromised patients who do not have a robust cellular immune response system, patients develop symptoms of active TB
What are the risk factors for latent and active TB?
Residents of prisons, nursing homes, homeless shelters
Co-infection with HIV
Close contact with pulmonary tuberculosis patients
What are risk factors for active TB?
Children < 2 years Elderly > 65 years Co-infection with HIV Malnutrition Immunosuppression
Where are possible sites of extra-pulmonary tuberculosis infection?
Bone, joint, spine, CNS
What are the signs and symptoms of tuberculosis?
Productive cough, hemoptysis, fever, fatigue, night sweats, weight loss
What are the radiological findings in a tuberculosis patient?
Infiltrates in the apical region
Cavitary lesions
How do you differentiate a tuberculosis patient from a pneumonia patient?
Differentiated from pneumonia by duration of symptoms: Tuberculosis - gradual onset (over weeks - months); pneumonia - acute onset (over hours - days)
Why does TB tend to produce infiltrates in the apical region?
M tuberculosis is an obligate aerobe, therefore they are oxygen loving and there is higher concentration of oxygen in the apical region of the lungs
(other bacteria tends to produce infiltrates in the middle or lower lobes)
Which high-risk groups are indicated for LTBI screening?
Children with recent TB contact HIV-infected individuals Patients considered for TNF antagonist therapy Transplant patients Dialysis patients
What are the two types of screening tests used to diagnose patients with latent TB?
Tuberculin skin test and interferon-gamma release assay
Describe the tuberculin skin test
Inject 0.1mL of tuberculin purified protein derivative (PDD) intradermally, read after 48-72 hours by a trained reader and read the diameter of induration (not area of redness)
Describe the interferon-gamma release assay
Blood collection into special tubes. Measures the interferon-gamma released by WBCs in response to incubation with M tuberculosis-specific antigens
In Singapore, what is the minimum positive tuberculin skin test
> =10mm
What group of patients lead to false negatives in both the tuberculin skin test and the interferon-gamma release assay?
Immunosuppressed (unable to mount an immune response)
What group of patients lead to false positives in the tuberculin skin test?
Those in contact with non-TB mycobacteria, and those with prior BCG vaccination
Advantages of interferon gamma release assay?
No false positive in BCG-vaccinated individuals, minimal cross-reactivity with non-tuberculosis bacteria, results available within few hours
What are the infection control considerations for LTBI patients?
None, as they do not have active disease and hence have no ability to transmit infection to others around
What are the infection control considerations for active pulmonary TB patients?
Need airborne precautions - negative pressure rooms, PPE
Airborne precautions are no longer needed after 2 weeks of effective treatment
In community, no need to avoid household members. Take TB medications, practice cough etiquette, ventilate homes
Prior to initiation of treatment for LTBI, what needs to be done?
Exclude active TB
Weigh risks vs benefit
What is the treatment options for patients with LTBI?
Isoniazid: 5mg/kg PO daily (do not exceed 300mg) for 6 months or 9 months (HIV) used with pyridoxine (10mg/day)
Rifampicin: 10mg/kg PO daily (do not exceed 600mg) for 4 months
Treatment of active TB in Singapore involves?
Mandatory reporting to the National Tuberculosis Registry
Singapore TB Elimination Program (STEP)
- Promotes DOT
- National Treatment Surveillance Registry
- Contact investigations
What does Singapore Tuberculosis Elimination Program comprise of?
- Direct Observed Therapy
- National Treatment Surveillance Registry
- Contact investigations
What are the tablet sizes for Rifampicin?
100mg, 300mg
What are the tablet sizes for Isoniazid?
150mg, 300mg
What are the tablet sizes for Pyrazinamide?
500mg
What are the tablet sizes for Ethambutol?
100mg, 400mg
What is the dose and maximum per dose for Rifampicin?
10mg/kg/day PO or 10mg/kg 3x/week PO
maximum: 600mg
What is the dose and maximum per dose for Isoniazid?
5mg/kg/day PO or 15mg/kg 3x/week
maximum: 300mg or 900mg
What is the dose and maximum per dose for Pyrazinamide?
15-30mg/kg/day PO
Maximum: 2g
What is the dose and maximum per dose for Ethambutol?
15-25mg/kg daily PO
Maximum: 1600mg
Which drugs in RIPE do not need renal dose adjustments?
Rifampicin, isoniazid
What needs to be considered before stepping down patient from intensive phase to continuation phase?
Confirmed susceptibility to RIF and INH
Culture negative pulmonary tuberculosis
Which medication is dropped in the 9 month regimen?
pyrazinamide (highly hepatotoxic)
Why is TB medications administered once daily?
TB medications exhibit concentration-dependent killing
Is rifampicin an inducer or inhibitor of CYP2C9?
Inducer
What are the risk factors for hepatotoxicity?
Age > 35 years, female, underlying liver disease, concurrent alcohol use, HIV
Which drugs in the RIPE treatment are known to cause hepatotoxicity and thus require monitoring?
RIP
How often do you need to check LFTs for a patient with >=1 risk factors for hepatotoxicity during treatment?
every 2-4 weeks
If a patient has no risk factors for hepatotoxicity, how do we monitor LFTs before and during treatment?
No need to monitor baseline LFTs before treatment and no need monitor LFTs during treatment
What is the lab findings of hepatotoxicity?
ALT > 3x ULN with symptoms
ALT >5x ULN with no symptoms
What is the management in LTBI treatment if hepatotoxicity develops?
Stop treatment immediately
Monitor LFTs
Re-challenge with INH when ALT improves to < 2x ULN
If patient can’t tolerate INH, switch to RIF x 4 months
What is the management in active TB treatment if hepatotoxicity develops?
Stop treatment immediately
Monitor LFTs
Re-challenge sequentially when LFTs normalised and symptoms resolved
If re-challenge fails, may need non-hepatotoxic regimen (EMB+FQ+STM)
How often to monitor visual acuity for patients started on ethambutol?
At baseline for all patients
Monthly monitoring in patients taking ethambutol for more than 2 months, or has renal insufficiency
