Tuberculosis Flashcards
Pathophysiology of M.TB infections
- How is it transmitted
Airborne transmission
- M.TB access lower airways
If consumed by macrophages –> No infection
If replicates in lungs –> Activates cellular immunity
Epidemiology of M.TB infections
In SG:
- Mostly foreign-born indvs
- # 5 cause of CAP (if unexplained cough for >= 3 weeks, should be evaluated for TB)
Risk factors for M.TB infections
Latent & Active
Latent & Active:
- Residents of prisons/homeless shelters/nursing homes
- Close contact with pulmonary TB patients
- Co-infection with HIV
Only Active:
- Child <2yo
- Elderly > 65yo
- Malnutrition
- Immunosupression
- Co-infection with HIV
Clinical presentation of M.TB
Primarily a PULMONARY infection
- If extra-pulmonary, treat longer + may need adjunctive therapy
Signs & Symptoms:
- Productive cough
- Hemoptysis (Cough out blood)
- Fever
- Fatigue
- Night sweats
- Weight loss
Note: Differentiated from pneumonia (eg. CAP) by duration of symptoms
(TB: Gradual onset; Pneumonia: Acute onset)
Radiological Findings:
- Infiltrates in apical region
- -> TB is an obligate aerobe, will likes where O2 is in (apical region)
- Cavitary lesions
Diagnosis of Active TB
Suspect based on:
- History
- Risk factors
- Clinical presentation
- Physical exam findings
- Chest X-Ray findings
If sputum for Ziehl-Neelsen stain for AFB is (+), treatment is initiated:
- 4-8weeks to grow & get confirmation of TB
- Another 4-6 weeks for drug susceptibility testing results
Diagnosis of Latent TB
Indication for latent TB screening
1) High risk group (Children with recent TB contact, HIV indvs, Pts considered for tumour necrosis factor antagonist therapy, transplant pts, dialysis pts) AND
2) Intent to treat if positive
Methods:
1) Tuberculin skin testing
- Read diameter of induration (by trained personnel)
(+) High sensitivity, low $, no need to collect blood
(-) False -ve (immunosuppressed), False +ve (BCG vaccination), Inter-reader variability. No universal acceptable std for interpreting results
2) Interferon-gamma release assay
- Measures interferon-gamma released by WBCs in response to incubation with M.TB specific antigens
(+) No false +ve, minimal cross-reactivity, results within hrs
(-) More $, need blood samples, False -ve (immunosuppressed)
Considerations for Infection Control
For active pulmonary TB patients:
1) Airborne precautions in hospitals
- (-)ve pressure rooms, PPE
2) Treatment to decrease infectiousness
- Generally no need airborne precautions after 2wks of effective treatment
3) Med compliance, cough etiquette, ventilate homes in community
- No need to avoid household members
Treatment of Latent TB
Prior to initiation need to:
- Rule out active TB
- Weigh risk vs benefit
Options:
1) Isoniazid: 5mg/kg PO daily (Max: 300mg)
- To co-administer with Pyridoxone (at least 10mg/day) to minimise neuropathy
- Duration: 6mths/9mths (HIV)
- Preferred regimen esp in pregnancy/lactation/HIV
- Don’t take with foods rich in tyramine/histamine
2) Rifampicin: 10mg/kg PO daily (Max: 600mg)
- Duration: 4mths
Alternative (but less evidence)
1) Isoniazid + Rifapentine: 900mg PO weekly
- Duration: 12 weeks
- MUST be given under DOT
- Not recommended for HIV patients
Treatment of active TB in SG
- Mandatory reporting to the National TB Registry
- STEP
- -> Promotes DOT
- -> National treatment surveillance registry
- -> Contact investigations
Which TB drugs require renal dosing adjustments?
Pyrazinamide, Ethambutol, Streptomycin
Standard treatment for PuLmonary Active TB
Standard: 6mth treatment
Intensive phase: 2mths daily
i) RIF (10mg/kg; 100/300mg tablets; Max: 600mg)
ii) Isoniazid (5mg/kg; 150/300mg tablets; Max: 300mg)
iii) PZA (15-30mg/kg; 500mg tablets; Max: 2g)
iv) EMB (15-25mg/kg; 100/400mg tablets; Max: 1600mg) OR STM IM (10-15mg/kg; 1g vial)
Confirm susceptibility to RIF & Isoniazid OR
Culture -ve pulmonary TB
Continuation phase: 4mths daily or 3x/week
i) RIF ( “ or 10mg/kg 3x/week)
ii) Isoniazid ( “ or 5mg/kg 3x/week)
9mth treatment
[If unlikely to tolerate PZA eg. elderly/liver disease]
Intensive phase: 2mths daily
i) RIF (10mg/kg; 100/300mg tablets; Max: 600mg)
ii) Isoniazid (5mg/kg; 150/300mg tablets; Max: 300mg)
iii) EMB (15-25mg/kg; 100/400mg tablets; Max: 1600mg)
Continuation phase: 7mths daily or 3x/week
i) RIF ( “ or 10mg/kg 3x/week)
ii) Isoniazid ( “ or 5mg/kg 3x/week)
Why can TB meds be given once daily?
Conc-dependent killing, all taken at same time
DDI of TB meds
Isoniazid: INHIBITS CYP2C19, 3A4, 2D6
Rifampicin: INDUCES CYP2C9, 2C19, 3A4 & PGP
Which TB meds can cause hepatotoxicity?
RIF, INH, PZA
Risk factors: Age > 35yo, female, underlying liver disease, concurrent alcohol use, HIV
Symptoms:
N/V, Unexplained fatigue, abdominal discomfort/pain
What to monitor for TB therapy
1) Monitoring of LFTs for hepatotoxicity
No risk factors: Not needed
> = 1 risk factor:
Before treatment: Check baseline LFTs
During treatment: Check LFTs every 2-4weeks
2) Monitor visual toxicity for Ethambutol
- Monitor visual acuity & colour discrimination tests @ baseline for all pts
- Monthly monitoring if patient:
i) Taking EMB for > 2mths OR
ii) Has renal insufficiency
