Anti-tubercular therapies Flashcards
What is the only evidence of tuberculosis?
a tiny, fibrocalcific nodule at the site of the infection
What is a latent infection?
viable organisms that are capable of infection that can remain dormant for decades
How can you tell if a person has a latent TB infections?
A tuberculin skin test will be positive but there is no disease
How can you tell if a person has an active TB infection?
- clinical signs and sx
- radiographic evidence
- bacteriological evidence
Describe the signs and sx of TB.
- pulmonary cavitation
- mycobacteria dissemination
- presence of bacilli in sputum
- malaise, anorexia, weight loss, fever
- increased sputum
extrapulmonary effects
Which bacteria cause TB?
Give some info about them.
mycobacterium TB - most frequent mycobacterium bovis - rare in developed nations found in TB cows and unpasteurized milk - oropharyngeal and intestinal TB
What are some characteristics of M. tuberculosis?
- acid-fast bacillus
- high lipid content of cell wall –> GM-
- slow growing
- resistant to drying, most antibiotics and host killing.
- intracellular survival
How is TB spread?
- by inhaled droplet nuclei
- once a droplet lands on something it is no longer infectious
What happens when TB droplets are inhaled?
- macrophages with kill the organism
2. macrophages will be unable to kill the organism –> replicates in the macrophage and lead to primary infection
Describe how reactivation happens.
- caused by a loss of balance between immune system and bacilli
- most often occurs in the lungs but can occur in lymph nodes, plural space, kidneys, gut, CNS
- pt will be symptomatic
- infectious if pt has pulmonary TB
Name 2 groups of people who are more likely to have a reactivation of TB
- pts with AIDS
- pts with HIV
What is TB therapy based on?
Stage
- latent or active
TB is primarily treated with antibiotics. Why is there such a higher amount of treatment failure and drug resistance?
- long duration of antibiotics with poor adherence
How long is a standard treatment for TB
- 6 months
- 9-12 months for TB meningitits
Why it the treatment so long for TB?
- a prolonged course of antibiotics is required to kill the semi-dormant and dormant organisms
Why is monotherapy not usually used?
because it allows selective growth of the resistant organisms and gives rise to drug resistance
What are the first line drugs for TB?
Isoniazid
Rifampin
Pyrazinamide
Ethambutol
What is the advantage of using both bacteriostatic and bactericidal drugs?
The bacteriostatic drugs will kill off the active bacteria while the bactericidal drugs will kill the dormant/semi-dormant bacteria
What does isoniazid do?
- bactericidal in extracellular area with high oxygen concentration
- prevents resistance by killing off rapidly growing bacilli
- high early bactericidal activity
What does rifampin do?
- bactericidal in extracellular areas
- ONLY drug that in bactericidal in fibrotic areas
- many drug-drug interactions
- without rifampin –> 18 months of tx required
What does pyrazinamide do?
- important in sterilizing semi-dormant bacteria
- active in acidic environment
- loses activity as inflammation resolves
- no benefit after 2 months
- allows 6 months of therapy when used with rifampin
What does ethambutol do?
- primarily used to prevent resistance to rifampin when primary resistance to isoniazid may be present
- D/C if organism sensitive to isoniazid
- DON’T use in renal failure or children
What are the 2 phases of TB standard tx regimen?
Intensive phase (0-8 weeks) Continuation phase (2-6 months)
What is the goal of the intensive phase?
to quickly kill the rapidly dividing organism to control disease and render the pt non-infectious and prevent emergence of drug resistance
What is the goal of the continuation phase?
- to sterilize the lungs by killing dormant/semi-dormant organisms to prevent relapse
- DOT allows for intermittent therapy
Which drugs are used during the intensive phase?
- all 4
- either 7/7 or 5/7
- ethamburol can be dropped if organism pansensitive
Which drugs are used during the continuation phase?
- isoniazid and rifampin twice a week
How is therapy carried out for pansensitive TB?
- duration = number of doses (tx will be extended in order to get all doses in)
With pansensitive TB, why would 9 months of therapy be needed?
- if pyrazinamide was NOT used in the first 2 months
- if culture results were positive at 2 months
What is the drug therapy used for latent TB?
- isoniazid daily for 9 months
- rifampin daily for 4 months
What are mycolic acids?
Which drug inhibits them?
- unique and essential mycobacteria cell wall components
- isoniazid and pyrazinamide
What happens if a pt develops abnormal LFTs on therapy?
- must hold TB meds until ALT returns to less than 2x the upper limit
What drug therapy do you use once a pt’s ALT level returns to less than 2x the upper limit
- restart rifampin alone or with ethambutol
- repeat ALT on day 3
- if ALT is still consider extending therapy to 9 months)
What is different in the TB treatment for pts with pre-exisiting liver disease?
- should avoid pyrazinamide
What is the TB drug therapy for a pt with cirrhoisis
rifampin + ethambutol +fluoroquinolon
Describe the TB drug therapy phases for a pt with renal insufficiency/ESRD
Intensive
- isoniazid/rifampin 1d after meal
-pyrazinamide/ethambutol 3x per week after meal
Continuation
- isoniazid/rifampin 3x per week after meals
what is the effect of rifampin on HIV medications?
It will decrease levels
How do you deal with decreased protease inhibitor levels in pts with HIV and TB?
- replace rifampin with rifabutin
How do you deal with decreased efavirenz levels in HIV pts with TB?
Increase the efavirenz dose
How do you deal with decreased raltegravir levels in HIV pts with TB
double the raltegravir dose
How does multi-drug resistant TB occur?
What is it defined as?
- course of antibiotics in interrupted
- levels of drug are insufficient to kill bacteria
- defined as resistance to rifampin and isoniazid +/- other drug
Which groups of pts does MDR-TB occur most easily?
- pts with HIV
- immunosuppressant drugs
What is the mortality rate of MDR-TB?
80%
What is extensively-drug resistant TB defined as?
- resistant to rifampin, isoniazid, any quinolon, any injectable 2nd line agent.
- 25% of MDR-TB pts have this
- makes TB essentially untreatable
Describe the drug therapy used in MDR-TB
- treated with a combo of 5-7 drugs
isoniazide + rifampin + pyrazinamide + ethambutol + aminoglycoside + fluoroquinolone + (cycloserine/ethionamide/aminosalicyclic acid)
How are the drugs administered for MDR-TB?
How long is therapy?
- daily injectables for first 2-6 months
- 3x/week injectables for 8 months
- total therapy = 20 months
How does bedaquiline work against TB?
it inhibits mycobacterium ATP synthase
potent against MDR-TB
How is bedaquiline used in MDR-TB therapy?
- used in combo with rifampin and pyrazinamide
- approved for use when other drugs are ineffective
What are the side effects of bedaquiline?
- liver toxicity
- prolonged QT
- chest pain
- hemoptysis (coughing up blood)
- nausea
- headache
