TB Flashcards
pathophysiology of mycobacterium TB
- 98% of cases are airborne transmission
- M.TB access the lower airways
~ no infection if: consumed by macrophages
~ with cellular immunity: replication in the lungs can be asymptomatic (latent) OR can become symptomatic (active)
obligate aerobic, slow-growing, acid-fast bacilli
waxy cell membrane - doesn’t produce typical gram-stain response (need Ziehl-Neelsen stain)
epidemiology of mycobacterium TB
~2/3 cases in pt > 50yrs
#5 cause of CAP: - any pt in SG with unexplained cough >= 3 weeks should be evaluated for TB
risk factors of latent M.TB infections
- Residents of prisons, homeless shelters, nursing homes
- Close contact with pulmonary TB patients
- Co-infection with HIV
risk factors of active M.TB infections
- Residents of prisons, homeless shelters, nursing homes
- Close contact with pulmonary TB patients
- Co-infection with HIV
- Children <2 yo
- Elderly > 65yo
- Malnutrition
- Immunosuppression
clinical presentation of pulmonary tuberculosis
- usually as a pulmonary infection
- extra-pulmonary TB is possible
~ e.g. bone and joint, CNS
treatment for extra-pul TB is similar to pul TB
- diff is that additional adjunctive therapy and longer duration treatment
clinical presentation of pulmonary TB (the signs and sx, radiological findings)
Signs and symptoms:
- Productive cough
- Hemoptysis (coughing out blood)
- Fever (systemic)
- Fatigue (systemic)
- Night sweats
- Weight loss
Radiological findings:
- infiltrates in the apical region (upper lobe of either lung vs bacterial pneumonia found in the middle/lower lobes)
How to differentiate pneumonia (e.g. CAP) from TB?
- Duration of symptoms
TB - gradual onset (weeks-months)
Pneumonia - acute onset (hours-days)
2 Procedures for LTBI screening
- Tuberculin skin test
- inject 0.1ml of PPD intradermally
- read after 48-72 hours by a trained reader
- read the diameter of induration (NOT area of redness)
- result: most sg’reans are BCG-vaccinated –> >= 10mm of induration
PPD = purified protein derivative
- Interferon-gamma release assay
- blood collection into special tubes
- measure interferon-gamma released by WBCs in response to incubation with M.tuberculosis - specific antigens in the tube
strengths and weaknesses of the 2 LBTI diagnosis screening
Tuberculin skin test (PPD): Strengths: - high sensitivity (95-98%) - low cost - no need to collect blood samples
Weakness:
- false negative = immunocompromised
- false positive = environmental contact with non-tuberculous mycobacteria, BCG vaccination
- no universally accepted standard for interpreting results
- inter-reader variability
Interferon-gamma release assay
Strengths:
- performance good as to PPD
- No false positive in BCG-vaccinated individuals
- Minimal cross-reactivity with non-tuberculous mycobacteria
- results available within few hours
Weaknesses:
- expensive
- need for blood samples
- false negative: immunocompromised
diagnosis of active TB
Suspect based on:
- History (TB is a gradual onset illness)
- Risk factors (immune status - HIV or diabetes, living conditions, nutritional status, age)
- Clinical presentation
- Physical exam findings
- Chest X-ray findings
if sputum obtained for Ziehl-Neelsen stain for acid fast bacilli (AFB) is positive, treatment is initiated
takes 4-8 wks to grow and get confirmation of TB
another 4-6 weeks for drug susceptibility testing results
what are the infection control requirements for TB
for LBTI patients:
- no special infection control precautions
for active TB patients:
- In hospitals: need airborne precautions
- negative pressure rooms
- need to wear PPE (gowns, N95 mask) - treatment decreases infectiousness
- airborne precautions no longer needed after 2 weeks of effective treatment - In community: no need to avoid household members
- take TB med, practice cough etiquette, ventilate homes
Patient-specific therapy for latent TB
monotherapy is ADEQUATE (progression risk from 10% to 1%)
before initiating therapy NEED to:
- exclude ACTIVE TB
- weigh risk vs benefits (if patients have underlying liver disease or risk of hepatotoxicity)
- Isoniazid 5mg/kg PO daily (max 300mg PO daily)
- 6 months or 9 months (HIV)
- to + 10mg/day pyridoxine
- can be used for preg, lactation, HIV - Rifampicin 10mg/kg PO daily (max 600mg PO daily)
- 4 months
- alt therapy for those who cannot tolerate isoniazid - Isoniazid + Rifapentine 900mg PO weekly
- not recommended for HIV pt
- DOT
- 12 weeks
why treatment of active TB is important?
Benefits the patient
- reduces number of replicating and persisting bacteria
- achieves durable cure and prevents relapse
- prevents development of resistance
Benefits public health
- minimised transmission to others
Patient-specific therapy for active TB
- Report to National TB Registry
- Sg TB Elimination Program (STEP): promotes DOT, National Treatment Surveillance Registry, investigate recent contacts
- STANDARD 6-month treatment
- 2 months Daily administration: RIF + INH + PZA + *EMB/STM
after confirming susceptibility to RIF and INH OR
culture negative pulmonary TB (assuming its susceptible to RIF and INH)
- 4 months Continuation Phase (daily or 3x/week administration): RIF + INH
(3x /week more convenient for DOT)
- 9-month treatment if unlikely to tolerate PZA (e.g. elderly, liver disease)
- 2 months intensive phase: daily RIF + INH + EMB
after confirming susceptibility to RIF and INH OR
culture negative pulmonary TB
- 7 months continuation phase: daily or 3x/week RIF + INH
Drugs involved: (1) Rifampicin (a) 10mg/kg daily (b) 10mg/kg 3x/week max per dose = 600mg available preparations: 100mg, 300mg tablets
(2) Isoniazid
(a) 5mg/kg daily
max per dose 300mg
(b) 15mg/kg 3x/week
max per dose = 900mg
available preparations: 150mg, 300mg tablets
RIF and INH no need renal dose adjustment
(3) Pyrazinamide
15-30mg/kg daily
max per dose = 2g
available preparations: 500mg tablets
(4) Ethambutol
15-25mg/kg daily
max per dose 1600mg
available preparations: 100mg, 400mg tablets
(5) Streptomycin IM
10-15mg/kg daily
max per dose 1g
available preparations: 1g vial
PZA, EMB and STM need to be renal dose adjustment
How do we administer the drugs for active TB treatment
- TB med = conc-dependent killing
- Administered once daily
- ALL taken at the SAME time
Look out for DDI:
- INH inhibits CYP2C19, 3A4, 2D6, 2E1
- RIF induces CYP1A2, 2C9. 2C19, 3A4 and PGP
- evaluate ALL medications closely (other prescription/ non-prescription/ supplements)
