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Tuberculosis - Coggle Diagram
Tuberculosis
Treatment
Empiric treatment with 4 first line treatment
- Isoniazid
- Rifampicin
- Pyrazinamide
- Ethambutol
- 2 months of intensive 4 drug therapy
- 4 months of Isoniazid and Rifampicin
- only suitable for suspectibility to isoniazid and rifampicin and pulmonary MTB
- Requires full adherence of daily high pill burden (~ 11 tabs/day)
- 3 times weekly is another regimen but not recommended
Aim of therapy:
- Rapidly kill growing bacteria
- Eradication
- Minimise transmission
- Avoid resistance
- Isoniazid: blocks mycolic acid synthesis in rapidly dividing cells. Good for actively dividing cells
- Side effects: peripheral neuropathy (treated with 25mg pyridoxine) and ance
avoid alcohol due to renal toxicity
- Rifampicin: inhibits bacterial DNA dependent RNA polymerase. Good against less active cells
- Side effects: potential hepatoxicity, red-orange urine and fluids and flu-like syndrome
- Ethambutol: inhibits mycolic acid cell wall formation
- protects isoniazid and rifampicin resistance
- Side effects: well tolerated but a rare potential for optic neuritis especially in children where they do not notice the change in vision.
Pyrazinamide: Works in necrotic conditions thus as tissue heals, it becomes less effective.
- Works by disrupting membrane but MOA is complex with multiple steps of deprotonation and protonation.
- Side effects: high risk of hepatotoxicty and gout
Vaccine and Prevention
Vaccine: a live atteunated M. bovis
- Highly effective in children and teens but lowered effect in adults
- TST prior to vaccine (may react strongly if previously exposed)
- Not recommended for universal use due to low incidence in Aus but recommended for ATSI children, healthcare workers and young children travelling to high incidence countries.
Latent Chemoprophylaxis: for those at high risk of converting to active TB
- Immunocompromised
- Younger than 35 years
- Recently exposed in last 2 years
- Treatment:
- Isoniazid 300mg daily for 6 months
- OR Rifampicin 600mg for 4 months
- OR Rifampicin + Isoniazid daily for 3 months
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Resistance
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Dual Resistance to Isoniazid and Rifampicin: Use Ethambutol or Pyrazinamide + 2 second line options (Levofloxacin + Streptomycin) IV for 20 months
Bedaquiline (Sirturo): New agent inhibits mycobacterial ATP synthesis
- Side effects: Major hepatotoxicity and cardiac toxicity.
Pretomanid: New MOA, Nitro-imidazole like and cell wall inhibition.
- Last Last line therapy in combination with Bedaquiline and Linezolid (BPaL)
- Very effective but very toxic
- Side effects: Potential respiratory poisoning (like cyanide)
Monitoring
Adherence mointoring on non-daily regimen
- orange discolouration for more than 6 hours after rifampicin dose
- Culture sputum monthly until negative
Ethambutol:
- Visual symptoms: changes in vision = cease immediately to prevent permanent damage.
LFTs and Renal Function:
- Those with pre-existing impairments.
- Weight changes
- patient may put on weight as they get better. As dosing is mg/kg, a dose adjustment is required.
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Classification
Organisms of Mycobacterium Tuberculosis complex in the lungs. Most frequent human mycobacterial pathogen.
- Small aerobic and slow dividing (divides every 16-20 hours)
- Gram-positive but stains negative in testing due to high lipid and mycolic acid content in cell wall
High prevalence globally with approximately 2 billion carriers but not all are active cases
- Aus has a notification on new cases
Transmission via sneezing and respiratory droplets
- between 2-6 microns evaporate prior to inhalation thus larger droplets will deposit in the lungs.
- but infects very slowly with 1 new infection per month.
- slow replicationup to 12 weeks
Pathogenesis
5% goes to active form whereas 95% remain latent
- Latent infections have a 5% chance of developing into active form or 50% with co-infection of HIV
- Treatment is 95% effective in curing with 5% relapse
- untreated = 50% death
Latent infections: macrophages presents and T-cells respond to form granulomas. It clamps the bacteria and straves it of oxygen and maintains as acidic environment which reduces its activity.
Active Infections: granulomas don't forms correctly and bacteria escapes.
- Aerobic conditions enhance growth whihc causes lung scarring and cavitation reducing lung function.
- Risk factors: HIV, Alcohol, extremes ages, immunosuppressant therapy
Co-infection (HIV)
Rifampicin: very potent 3A4 inducer, interaction with HIV therapy - PK boosters cancelled.
Rifabutin: Less induction but also less active vs rifampicin
Rifapentine: not used in HIV co-infection
Careful IRIS - Initating ART can restore the immune system function and leads to full body immune response.
- Preventing high HIV load in the first place is key
- If CD4 count is low - we gamble between IRIS and reduced survival due to HIV
- If CD4 count is adequate, we can delay ART, address TB with 2 months of intensive regimen first then start ART.
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