Tuberculosis Flashcards
Describe the morphological characteristics of Mycobacterium tuberculosis.
Slow-growing, obligate aerobic, acid-fast bacilli with thick, waxy cell membrane that does not produce a typical Gram-stain response
- Makes diagnosis of TB particularly challenging since it takes 4-8 weeks to confirm growth
Explain the pathophysiology of tuberculosis.
98% of TB cases are via airborne transmission.
M. tuberculosis access the lower airways & are consumed by pulmonary macrophages, which usually results in no infection.
However, in some instances, it can replicate in the lungs, resulting in cellular immunity.
Presents as either asymptomatic (i.e. latent TB) or symptomatic TB (i.e. active TB).
What is your recommendation when an individual is presented with an unexplained cough for more than 3 weeks at the community pharmacy?
Refer for evaluation of TB.
What are some risk factors associated with TB?
Latent & Active:
- Residents of nursing homes, prisons, homeless shelters due to frequent contact with healthcare system
- Close contact with pulmonary TB pt
- Co-infection with HIV
- Living in urban areas
Active:
- Children < 2 y/o
- Elderly > 65 y/o
- Malnutrition -> weakened immune system
- Immunosuppression
What are some clinical presentations in a patient with a likely tuberculosis infection?
Primarily pulmonary infection; extrapulmonary TB is possible (identical to pulmonary TB Tx but longer) e.g. bone & joints, spine, CNS etc.
Signs & symptoms include:
Local - Productive cough, hemoptysis
Systemic - Fever, fatigue (generalised; malaise), night sweats, weight loss
Night sweats & weight loss are classical smx of TB.
Radiological findings (classical):
Infiltrates in apical region (obligate aerobe)
- vs pneumonia: usually lower/middle lobes
Cavitary lesions
How do the symptoms of pneumonia compare with those of TB?
TB: Gradual onset (weeks - months); apical infiltrates in CXR
Pneumonia: Acute onset (hours - days); dense infiltrates in middle/lower lobes usually in CXR
What are the conditions in which an individual is indicated for latent TB infection (LTBI) screening?
High-risk group AND intent to treat if positive
High-risk group includes:
- Children w/ recent TB contact (lifelong with increasing risk with age)
- HIV infected individuals
- Pt considered for tumour necrosis factor antagonist Tx
- Transplant pt
- Dialysis pt (frequent encounter w/ hospital settings increase TB risk)
Why is LBTI NOT empirically treated for non-high-risk groups, despite being positive for LTBI?
1) RIPES have multiple side effects which have risks outweighing the benefits of Tx.
2) Reactivation of latent TB happens over time; pt w/ life-limiting diagnosis (e.g. end-stage cancer) may not need LTBI Tx due to significant toxicity.
What are the tests available to diagnose a patient with LTBI?
1) Tuberculin skin test (e.g. Mantoux test, tuberculin purified protein derivative [PPD] test)
- Inject 0.1 mL of PPD intradermally & read after 48-72h by a trained reader/nurse.
- Read diameter of induration (NOT redness)
- Positive PPD >= 10mm since most SG are BCG-vaccinated
2) Interferon-gamma release assay (e.g. QuantiFERON-TB Gold, T-SPOT.TB)
- Blood collection into special tubes
- Measures interferon-gamma released by WBC in response to incubation of M. tuberculosis-specific agent
What are some advantages of using interferon-gamma release assay over tuberculin skin test for the clinical diagnosis of LTBI?
Results available w/in few hours vs 48-72h
No false positives in BCG-vaccinated individuals, unlike tuberculin skin test
Minimal cross-reactivity w/ non-TB mycobacteria, thus no false positives in interferon-gamma release assay
What is a common limitation between the use of interferon-gamma release assay and the tuberculin skin test for the clinical diagnosis of LTBI?
False negatives due to immunosuppression in patients; unable to mount sufficient immune response for significant results.
How is active TB clinically diagnosed?
Suspect based on:
- History
- Risk factors
- Clinical presentation
- Physical exam findings
- CXR findings
If sputum obtained for Ziehl-Neelsen stain for acid-fast bacilli is positive, Tx is initiated before confirmatory microbiological test results are obtained.
- Takes 4-8 weeks to grow & confirm TB
- Takes another 4-6 weeks for Abx susceptibility test results
What are some infection control precautions to be taken when treating pt with LTBI & active TB?
LTBI: No special infection control precautions since asymptomatic
Active TB:
- Airborne precautions in hospital w/ negative pressure rooms & compulsory donning of PPE
- Tx decreases infectiousness; thus, after 2 weeks of effective Tx, can drop airborne precautions
- No need to avoid household members in community, since already exposed; take TB medications, practice cough etiquette, ventilate homes
What are some considerations in the treatment approach of LTBI?
Monotherapy is adequate.
Prior to initiation of LTBI Tx:
1) Should exclude active TB; otherwise, greatly increase risk of developing resistance against TB
2) Weigh risk vs benefit (including SE of RIPES such as hepatotoxicity)
CD is a 38 y/o 70kg male who is required to undergo a purified protein derivative (PPD) test as part of his pre-employment screening. The test was performed on his right forearm which resulted in a 1.5cm induration. CD is otherwise healthy with all labs within normal limits. He is born in Singapore and received all the recommended childhood and adult vaccinations. Recommend the most appropriate treatment to CD for his LTBI.
Isoniazid PO one 300 mg tab (5 mg/kg/day) OD w/ PO pyridoxine 10mg/day for 6 months
- Pyridoxine is co-administered to minimise neuropathy from isoniazid.
Required dose = 5 mg/kg x 70kg = 350mg, but only 150mg & 300mg tablet formulations are available, thus 300mg tablet is given instead.
No HIV, thus Tx duration is 6 months (instead of 9 months for HIV pt).
AB is a 35 y/o 70kg male who is required to undergo a purified protein derivative (PPD) test as part of his pre-employment screening. The test was performed on his right forearm which resulted in a 1.5cm induration. His HIV infection is well-controlled and is otherwise healthy with all labs within normal limits. He is born in Singapore and received all the recommended childhood and adult vaccinations. Recommend the most appropriate treatment to AB for his LTBI.
Isoniazid PO one 300 mg tab (5 mg/kg/day) OD w/ PO pyridoxine 10mg/day for 9 months
- Pyridoxine is co-administered to minimise neuropathy from isoniazid.
Required dose = 5 mg/kg x 70kg = 350mg, but only 150mg & 300mg tablet formulations are available, thus 300mg tablet is given instead.
Tx duration is 9 months instead of 6 months for HIV pt.
EF is a 37 y/o 70kg male who is required to undergo a purified protein derivative (PPD) test as part of his pre-employment screening. The test was performed on his right forearm which resulted in a 1.5cm induration. EF has reported being intolerant of isoniazid but is otherwise healthy with all labs within normal limits. He is born in Singapore and received all the recommended childhood and adult vaccinations. Recommend the most appropriate treatment to EF for his LTBI.
Rifampicin PO two 300mg tabs (10mg/kg/day) OD for 4 months
Required dose = 10 mg/kg x 70kg = 700mg, but only 100mg & 300mg tablet formulations are available, thus two 300mg tablets are given instead.
Max daily dose of rifampicin = 600mg
What are the treatment goals for active TB therapy?
Reduce no. of replicating & persisting bacteria in pt.
Achieves durable cure & prevent relapse
Prevents development of Abx resistance
Minimise transmission to others (protect public health)
Isoniazid + rifapentine 900mg PO weekly for 12 weeks is the preferred therapy for HIV patients diagnosed with LTBI. True or false?
False! Isoniazid + rifapentine MUST be given under directed observed therapy (DOT) & is NOT recommended for HIV patients.
Thus, it is NOT considered as first-line therapy for LTBI.
All active TB patients receiving treatment must be reported to the National Tuberculosis Registry by law. True or false?
True
Explain “directly observed therapy”.
DOT requires direct observation of trained healthcare professionals to enact therapy, and does NOT permit direct supervision by patient’s family members/friends.
Which of the following first-line anti-TB drugs requires renal dose adjustments in patients with chronic kidney diseases who are treated for active TB infection?
Pyrazinamide
Ethambutol
Streptomycin
List the maximum daily (or weekly) dose of all first-line anti-TB drugs.
RIF: max 600mg daily/weekly (for both dosing regimens)
INH: max 300mg daily (for OD administration) OR max 900 mg daily (for x3/week administration)
PZA: max 2g daily
EMB: max 1600mg daily
STM: max 1g daily
List the available preparations of all first-line anti-TB drugs.
RIF: 100mg & 300mg tablets INH: 150mg & 300mg tablets PZA: 500mg tablets EMB: 100mg & 400mg tablets STM: 1g injection vial
List the usual doses of all first-line anti-TB drugs.
RIF: 10mg/kg/day or 10mg/kg 3x/week INH: 5mg/kg/day or 15mg/kg 3x/week PZA: 15-30 mg/kg/day EMB: 15-25 mg/kg/day STM: 10-15 mg/kg/day
RR is a 54-year-old male with weight loss and hemoptysis at home. Upon admission, his CXR shows cavitary lesions and his sputum culture is found to have a positive AFB stain. His weight is 72kg and all labs are normal. Recommend an appropriate treatment to EF for his TB.
Intensive Phase (2 months): RIF 600mg PO OD + INH 300mg PO OD + PZA 1100-2000mg PO OD + EMB 1100-1600mg PO OD + pyridoxine 10mg/day PO OD
Followed by Continuation Phase (4 months):
RIF 600mg PO 3x/week + INH 900mg PO 3x/week + pyridoxine 10mg/day PO OD
- After confirmed susceptibility to RIF & INH OR culture negative pulmonary TB has been confirmed
YY is a 70-year-old male with weight loss and hemoptysis at home. Upon admission, his CXR shows cavitary lesions and his sputum culture is found to have a positive AFB stain. His weight is 72kg and all labs are normal. Recommend an appropriate treatment to YY for his TB.
Intensive Phase (2 months): RIF 600mg PO OD + INH 300mg PO OD + EMB 1100-1600mg PO OD + pyridoxine 10mg/day PO OD - Dropped PZA due to elderly who is unlikely to withstand hepatotoxic SE of PZA (liver disease is another reason)
Followed by Continuation Phase (7 months):
RIF 600mg PO 3x/week + INH 900mg PO 3x/week + pyridoxine 10mg/day PO OD
- After confirmed susceptibility to RIF & INH OR culture negative pulmonary TB has been confirmed
As anti-TB drugs exhibit concentration-dependent killing pharmacokinetics, it is recommended to administer all anti-TB drugs at the same time where possible. True or false?
True
Which first-line anti-TB drug is known as a CYP3A4 inducer?
Rifampicin
Which first-line anti-TB drug is known as a CYP3A4 inhibitor?
Isoniazid
YP is a 27-year-old female receiving a standard 4-drug tuberculosis regimen at appropriate doses for her body weight. She has no past medical history and does not consume alcohol. Recommend an appropriate monitoring plan to YP.
Check baseline LFTs & repeat LFTs every 2-4 weeks.
Risk factors to recommend LFTs monitoring for LTBI or active TB include:
- Age > 35 y/o
- Women
- Underlying liver disease
- Concurrent alcohol use
- HIV
Take baseline visual acuity & colour discrimination tests on EMB initiation.
- Monitor for any pt complaints on reduced visual acuity & reduced red-green colour discrimination.
AP is a 23-year-old male receiving a standard 4-drug tuberculosis regimen at appropriate doses for his body weight. He has no past medical history and does not consume alcohol. Recommend an appropriate monitoring plan to AP.
No need to check baseline LFTs nor routine LFTs monitoring.
Monitor only for smx of hepatotoxicity & check LFTs if concerning smx occur.
Take baseline visual acuity & colour discrimination tests on EMB initiation.
- Monitor for any pt complaints on reduced visual acuity & reduced red-green colour discrimination.
Which first-line anti-TB drugs are known to be hepatotoxic?
RIF, INH & PZA
HJ is a 37-year-old male receiving a standard 4-drug tuberculosis regimen at appropriate doses for his body weight. He has no past medical history and does not consume alcohol. Recommend an appropriate monitoring plan to AP.
Check baseline LFTs & repeat LFTs every 2-4 weeks.
Risk factors to recommend LFTs monitoring for LTBI or active TB include:
- Age > 35 y/o
- Women
- Underlying liver disease
- Concurrent alcohol use
- HIV
Take baseline visual acuity & colour discrimination tests on EMB initiation.
- Monitor for any pt complaints on reduced visual acuity & reduced red-green colour discrimination.
What are some symptoms patients should look out for during the treatment period when taking first-line anti-TB drugs for their TB infections?
Symptoms of hepatotoxicity:
N/V, unexplained generalised fatigue, abdominal pain or discomfort
Symptoms of visual toxicity:
Reduced visual acuity & reduced red-green colour discrimination.
If present, stop Tx immediately for ALL anti-TB drugs and seek medical attention immediately.
What laboratory results are used to identify whether a patient has developed hepatotoxicity from anti-TB drugs?
ALT > 3x ULN w/ symptoms OR
ALT > x5 ULN w/o symptoms
Describe how a patient who developed hepatotoxicity while on anti-TB drugs for LTBI is managed.
- Stop Tx immediately.
- Monitor LFTs once to twice a week
- Re-challenge with INH when ALT improves to < 2x ULN
- If pt cannot tolerate INH or develop hepatotoxicity again, switch to RIF 10mg/kg/day PO OD x 4 months
Describe how a patient who developed hepatotoxicity while on anti-TB drugs for active TB is managed.
- Stop Tx immediately.
- Monitor LFTs once to twice a week
- Re-challenge sequentially with one anti-TB drug at a time when ALT normalised & hepatotoxic symptoms resolved
- If rechallenge failed or develop hepatotoxicity again, may need to switch non-hepatotoxic regimen (e.g. EMB + FQ + STM -> last resort)
For patients on EMB, what should we monitor for during the course of Tx?
Monitor for visual acuity & colour discrimination tests
- EMB reduces visual acuity & reduced red-green colour discrimination
- Check baseline for all pt before EMB initiation
- Monthly monitoring in pt w/ following risk factors: taking EMB for > 2 months (unlikely) OR renal insufficiency (e.g. CKD)
Educate all patients to stop TB Tx & seek medical attention immediately if they experience changes in vision.
