TB Flashcards
MDR-TB
multi drug resistant TB
bacteria that causes TB
mycobacterium tuberculosis
What type of bacteria is mycobacterium tuberculosis?
- aerobic (needs O2)
- G+ve
- acid fast (stain not removed by acid)
- bacilli
What does intracellular mean (about mycobacterium tuberculosis)?
able to survive inside macrophages
structure of mycobacterium tuberculosis
- layer of mycolic acid surrounds the cell
- gives it a waxy, waterproof coating
- difficult to penetrate by ABX - resistance
How is TB transmitted?
aerolised droplets from infected patient
inhaled into alveoli of new host
outcomes TB can have
– Primary Tuberculosis (first infection)
– Complete clearance
– Post-primary Tuberculosis (re-infection)
– Active Tuberculosis
– Latent Tuberculosis
first infection of TB
- Mostly affects lungs
- Usually clinically silent in immunocompetent
- Results in an area of granulomatous inflammation, shadow on an x-ray, called Ghon focus.
- 90% will never develop active disease due to good immune response
latent TB
- bacillus can stay trapped inside the granuloma in some patients
- skin prick test to ID latent TB
- can reactivate any time, from abnormalities in cell mediated immunity
- long ABX regimens used to get rid of latent TB
What test to detect latent TB?
skin prick test - tuberculin test
active/post primary active TB
- small no. develop at 1st aquisiton
- more commonly reactivation of latent TB infection
- can occur if become immunocompromised (HIV, cs, chemo)
- aggressive immune system reaction
- large granulomas with ‘cheesy’ contents called caseation
- coughed up (incl live bacteria) leaving large lesions, seen on x-ray
- lesions become pus filled, can exudate
- ideal breeding ground for bacillus and large nos. released
- active = contagious
What is extrapulmonary TB?
- can cause disease at any site of body
- usually from reactivation of latent infection
common sites:
- lymph nodes
- GIT
- bone
- CNS
- eg. Miliary TB
What is disseminated disease? (Miliary tuberculosis)
- bacilli transported in blood or lymphatic system
- can develop as primary infection or post primary reactivation
- can affect many organs
- can cause diagnostic delay, esp if lungs not infected
- more common in children and immunocompromised
- CXR look like small seeds
presentation of active TB
initial Sx vague/non-specific
cough - persistent, productive
weight loss
fever
night sweats
fatigue
dyspnoea
chest pain
haemoptysis
(depends on site of infection, 60% respiratory)
people who are at inc risk of TB
- born in high prevalence area
- immunocompromised
- contact with active TB
- previous TB Tx
- alcohol/drug misusers
- settled migrants in UK
diagnosis of TB
respiratory
- CXR
- acid fast bacilli test
- sputum cultures
- NAAT (nucleic acid amplification test), often PCR
non respiratory
- biopsy/needle aspiration (culture)
- MRI/CT/ultrasouns
- CXR (confirm/exclude respiratory disease)
diagnosis of TB
respiratory
- CXR
- acid fast bacilli test
- sputum cultures
- NAAT (nucleic acid amplification test), often PCR
non respiratory
- biopsy/needle aspiration (culture)
- MRI/CT/ultrasouns
- CXR (confirm/exclude respiratory disease)
INITIAL management of pulmonary TB
- TB specialist
hospital - isolated
- PPE
- -ve pressure room if MDR-TB
community
- advise highly contagious when active
- no work/school/crowded places
- face mask in public during first 2 weeks of Tx
phases of TB Tx
- intensive/initial phase Tx
- continuation phase
intensive/initial phase Tx
lasts 2 months
with 4 drugs
continuation phase Tx
4-7 months
with 2 drugs
drugs in initial Tx
rifampicin
isoniazid (with pyridoxine)
pyrazinamide
ethambutol
-> for 2 months
drugs in continuation Tx
rifampicin
isoniazid (with pyridoxine)
-> for further 4 months
Why is combination of drugs used?
to reduce risk of resistance
MOA of rifampicin
- bactericidal
- blocks RNA polymerase and prevents protein formation
rifampicin and food
- absorbed in the GIT
- reduced if taken with food
- take on empty stomach
s/e of rifampicin
- red/orange disconoration of body fluid (stains contact lenses)
- liver damage (inc liver enzymes, 4x ULN STOP Tx)
- enzyme inducer
s/e of rifampicin
red/orange disconoration of body fluid
- stains contact lenses
liver damage
- inc liver enzymes
- 4x ULN then STOP Tx
isoniazid MOA
- inhibits synthesis of mycolic acids required for cell wall
- bactericidal
- acts rapidly to reduce initaial bacterial load
metabolism of isoniazid
by liver
acetylation
- some people fast metabolisers, some slow
- affects t1/2
Who is more likely to have adverse effects with isoniazid?
slow acetylates
advanced HIV
of isoniazid
- hepatotoxicity
- N&V
- hypersensitivity rxn
- peripheral neuropathy
How to avoid PN with isoniazid?
supplement with vitamin B6 -> pyridoxine
Why does pyrazinamide no longer become effective later in therapy?
- pyrazinamide only works in acidic pH, inside the macrophages in the tubercle (nodules of dead cells filled with TB bacteria)
- no. of these decrease later in therapy
- it no longer becomes effective
Is pyrazinamide bacteriostatic or bacteriocidal?
bacteriostatic
adverse effects of pyrazinamide
hepatotixicity
rashes
urticaria
gout
pyrazinamide and hepatotoxicity
- elevation of LFTs
- regular LFTs
Sx of liver disease
- N&V
- malaise
- jaundice
