3. Contents…..
• What is tuberculosis?
• Epidemiological details: Incidence, prevalence, causative agent, host, risk factors
• Pathophysiology of tuberculosis
• Clinical outline: Symptoms & Sign, type to tuberculosis, approach towards
diagnostic confirmation,
• Antitubercular drugs: first line AKT, 2nd line AKT
• Management of tuberculosis: RNTCP program for different types of tuberculosis
• Special consideration: Pediatric Tb, Tb in pregnancy
3
4. What is tuberculosis??
Tuberculosis (TB) is a chronic granulomatous disease caused by mycobacterium
tuberculosis.
It can affect almost any part of the body but primary site is lungs.
As per “WHO” Tuberculosis also called as “ Wasting disease” (pronounced weight loss)
and the “White plague.”
• Neo-latin word : - Round nodule/Swelling
- Condition
“Tubercle”
“Osis”
4
5. TUBERCULOSIS….Epidemiology…..
• TB is the 13th leading cause of death and the second leading infectious killer after COVID-19
(above HIV/AIDS).globally (2018 WHO report)- 2.2 million from India- highest contribution.
• Govt: RNTCP- Revised National Tuberculosis Control Programme: provide free treatment by
government to all TB cases
• On December 30,2019 National Tuberculosis Elimination Program (NTEP) with commitment to
eliminating TB in the country by 2025.
• 2012- NOTIFIABLE disease
• New challenges: HIV- TB infection, MDR TB cases, XDR TB
5
7. 1. Causative Organisms:
it is caused by mycobacterium tuberculosis
Mycobacteriumtuberculosis
Human
Mycobacterium Bovis
Animals
Myco- waxy
appearance- due to
highly lipid
containing cell wall
Bacterium- slender
shape bacillus
7
8. Other causative organisms……..
Mycobacterium africanum
Mycobacterium microti
Non-Mycobacterium Genus
Mycobacterium leprae
Mycobacterium avium
Mycobacterium asiaticum M.
africanum
M. Bovis
M. Canetti
M. microti
M. tuberculosis complex
8
9. 1. Mycobacterium tuberculosis Characteristics…….
Obligate aerobic – grows successfully in oxygen rich tissue like lung,
Non spore forming, Non motile
Facultative intracellular pathogen: usually affect mononuclear
phagocytes( macrophage)
Very slow dividing bacteria – 15-20 hrs
Gram positive rods:
Hydrophobic : Lipid rich cell wall –contain mycolic acid- 50% of
dry weight of cell - Confers many bacterium’s characteristic
- impermeable to dye/stain
- Acid fast- retain acidic stain
- Responsible for resistant to antibiotics
- Resistant to oxidation & survive inside macrophage
- Resistant to lysis by complement system 9
10. • 2. Risk factors
• Immune system can often successfully
fight TBbacteria.
Diseases and medications can weaken
your immune system, including :
• Malnutrition
• Advanced age
• Alcoholism
• Diabetes
• Immunosuppressive medications
• HIV/AIDS & Chemotherapy
• Immigrant (From area with high TB
incidence )
• 3. Transmission & Spread……
• Airborne infection….
• spread by Droplet Infection/
inhalation/ingestion/ placental transfer
10
11. Pathophysiology of tuberculosis…
M.Tuberculosis in inhalation
Enters Host
Lung
Utilizes
Alveoli
Cholesterol in cell membrane (Highly oxygenases amount involved in
metabolism of cholesterol into)
e-
Engulfed by alveolar macrophages and converted into phagosome-
Phagolysosome – M. TB inhibit fusion of Phagosome to lysosome –don’t undergo
degradation
ATP
In lungs- high O2 rich and
oxygenase and best thrive at apex as
have high Oxygen tension.
11
12. Some of Macrophages with I/c MTB express Antigen presenting cell (APC)
APC containing expressed MTB antigen enters lymphatic system and reaches lymphatic
organs.
Activation of TH1cells(Cell mediated Immunity)- Activation of INF-γ on endothelial cells of
blood vessels
Monocyte Adherent Protein (MAP) on endothelium --adherence of monocyte
Squeezing of monocytes from blood to site of injury –converted to Macrophages and increases
in number at alveoli
Granuloma (A group of cluster of epithelioid cells surrounded by rim of lymphocytes
around them Multinucleated giant cells by fusion of adjacent cells (Langhans type)
12
13. 13
1. M.TB entry in lung
2. Inside macrophage
3. Inside lymphatic syste &
Activation of TH1 cells
4. INF on endothelial cell –
MAP – adhesion of monocyte
to endothelium
4a. Squeezing of monocyte
from blood vessels to site of
injury
4b. Monocyte converted into
macrophage – epithelioid cells –
Giant cells
5 Granuloma formation
6 Granuloma located at alveoli
7 Sputum
14. Granuloma consist of macrophage and
Surrounding by the epithelioid cells and giant cells there is a zone of
lymphocytes, plasma cells, and fibroblasts. Hard tubercle: (due to
absence of central necrosis)
Within 10-14 days, the center of the cellular mass undergoes necrosis
CASEATION NECROSIS (soft tubercle)
Wide spread of Soft tubercle over various parts of alveoli and lungs
causes -PULMONARY TB.
Newly formed granulomas damages tissue and degenerates tissue
surrounding
Extensive spread and damage of various parts of body occurs. This
condition is called MILIARY TUBERCULOSIS.
14
15. When infected person coughs or sneezes, the granulomas that may be present
in sputum comes in contact with air.
Lymphocytes, fibroblasts surrounding the cluster of epitheloid cells become inactivated.
And Mycobacterium tuberculi gets free from epitheloid cells
Comes in contact with another person
Through inhalation
New person develops TB
15
17. Type of tuberculosis..
Pulmonary TB Extra pulmonary TB
Less common forms
i. Lymph node TB
ii. Pleural TB
iii. Skeletal- bone TB
iv. Genitourinary TB
v. Miliary TB
vi. Pericardial TB
vii. Gastrointestinal TB
viii.Tuberculous Meningitis
17
21. Specimen
Fresh Sputum
Pleural Fluid
Cerebrospinal Fluid
Urine
Biopsy Material
Gastric Washing
Blood.
21
• 1.Smear test:
a. Zeihl-Neelsen stain
b. Auramine stain(fluorescence microscopy)
• 2. Sputum culture test:
a. Lowenstein –Jensen(LJ) solid medium: 4-
14days
b. Liquid medium : 8-14 days
c. Agar medium : 7 to 14 days
Gold
Standard for
diagnosis
23. Tuberculin skin test (PPD)
Injection of fluid into the skin of the lower arm.
48-72 hours later –checked for a reaction.
Diagnosis is based on the size of the wheal.
1 dose = 0.1 ml contains 0.04µg Tuberculin PPD.
23
28. How to describe any antitubercular drug????
• Action of drug –Bacteriostatic/ Bactericidal
- Extracellularly-E/C (fast multiplying) , Intracellularly –
I/C, (Slow multiplying), Dormant
- Effective against Acidic (active lesion) / alkaline
medium (in Caseous material)
• Mechanism of action:
• Resistant : Incidence, mechanism of resistant
• Pharmacokinetic: tissue distribution, drug drug interaction
• Dose
• Adverse drug reaction
28
29. …So in granuloma, there are
subpopulation need to be affected by
drugs
1. Fast growing- within wall of cavity-
high O2-neutral PH-E/C
2. Slow growing – at inflamed side- I/C –
multiply at low PH (Acidic PH)
3. Spurters- within caseous material – PH
neutral- bacilli grow intermittently -
occasionally active
4. Dormant- inactive for prolonged
period- no drug work on that
Active lesion Neutral PH
Caseous material
I/C – acidic PH
29
31. • Mechanism of resistant:
• 1 in 106 tb bacilli inherently resistant
• Mutation in CATALASE – PEROXIDASE
GENE (Kat G)- most common mechanism-----
stop INH
• Mutation in kasAgene
• Mutation in InHa gene: Over-expression of the
inhA & aphC gene (detoxify organic peroxide)-
Overcome by “High dose INH)
• Global INH resistant- 7.4%, India: 18%
• NO CROSS RESISTANT to other
ANTITUBERCULAR drugs
Mechanism of action
Isoniazide
Catalase peroxidase (enzyme of
mycobacterium) activates
reactive metabolite Adducts with
NAD
InH a Kas a dihydrofolate
reductase
Inhibition of Inhibition of
Mycolic acid DNA synthesis
Bactericidal action
NADP
31
①
②
32. 1. Isoniazid ( Isonicotinic acid hydrazine, H)
• Excellent , Cheapest and essential component of antiTB regimen
• Action on : - Bactericidal
- kill fast multiplying
- inhibit slow multiplying
- E/C, I/C
- Equally effective against acidic/ alkaline media
• Mechanism of action : Mycolic acid synthesis inhibition –unique fatty acid
component of mycobacteria- high selectivity of INH to bacteria
32
33. •P/K
Absorption: Completely absorbed
Distribution: Penetrate all body tissues, tuberculous cavities, meninges, placenta
Metabolism: Liver- N acetylation – Determine ADR but not affect efficacy
• Rate of acetylation depends-
- Slow acetylators (30-40% Indian-(Half life- 3h)- TOXICITY
- Fast acetylators (60-70% Indians- Half life-1h)- THERAPEUTIC FAILURE
- Daily regimen: don’t affect
- But biweekly regimen are less effective in fast acetylator.
- ADR- common in slow acetylator
• DI: H- retard absorption of Phenytoin, CPZ, warfarin, theophylline
33
34. INH: ADR
Dose related ADR
1. Peripheral Neuritis:
Dose related- More with higher dose
Due to interfere with inhibition of pyridoxin utilization
More observed in – diabetics, alcoholics, malnourished, pregnant
& lactating mother
Start prophylaxis – pyridoxin -10mg/ day
Treatment - pyridoxin -100mg/ day
2. Hepatotoxicity : Major dose related ADR:
Common in adults/ alcoholics- abdominal symptoms- go for LFT-
Stop drug- reverse on stopping
Non dose related
Rashes,
anemia,
lethargy,
arthralgia
35
Dose: In adult– 300mg O.D or 5mg/kg/day
35. 2. Rifampin (Rifampicin/ R )
• Semisynthetic derivative of antibiotic- Rifamycin- obtain from bacteria- streptomyces
mediterranei
• Spectrum of Action:
Bactericidal
M. TB: Highly efficacious like INH- affect all subpopulation
E/C, best I/C (slow dividing), (intermittently dividing) Spurters
Good sterilizing & resistant preventing action
M. leprae
Gram+Ve (Staph)
Gram-Ve (E/K/Pse/Pr, legionella, N.Meningtidis H. influenzae)
36
36. • Mechanism of action: Rifampicin
Inhibition of R.N.A
synthesis
Tuberculocidal effect
• Don’t bind to mammalian RNA polymerase
• Resistant: less 10-6 Unusual
• rpoB gene mutation – affinity to drug
• Cross resistant to only congeners not to other AKT
Binds to the β subunit of DNA-dependent RNA polymerase
(rpoB) .
• P/K
• Absorption: food
bioavailability- always
taken in EMPTY
STOMACH
• Widely distributed-
Case/I/c, placenta
• Metabolism : Liver –
EHC
37
37. • Rifampicin: Drug Drug interaction
Microsomal enzyme inducer - Increases level of below enzyme and hasten metabolism-
decrease therapeutic concentration and therapeutic failure result
CYP3A4, CYP2D6, CYP450, CYP1A2, CYP2C
Enhances its own metabolism – other drugs like
- warfarin
- OC Pills (failure of contraception)
- Sulfonylureas (hyperglycemia not controlled)
- Corticosteroid (therapeutic failure)
- HIV Protease inhibitors (NNRTIs)
- Theophylline, Clarithromycin
- Metoprolol
- Antifungal (fluconazole, ketoconazole)
- Phenytoin
Therapeutic failure
Need to increase
dose
38
38. Adverse drug reaction: Rifampicin
FLU like symptoms: Minor-
don’t require drug withdrawal
Hepatitis- Dose related –
With preexisting condition
Stop drug – Reversible
Cutaneous : Flushing, Pruritus
+Rash on face and scalp, redness –
Don’t require withdrawal of drug
Abdominal symptoms:
Don’t require drug withdrawal
39
39. • Dose: 600 mg OR 10 mg/kg OD Oral
Therapeutic uses of rifampicin
• TB: Standard regimen of RNTCP for sensitive TB cases
• Brucellosis – in combination with doxycycline (first choice combination)
• Leprosy – in combination with dapsone
• Prophylaxis of meningitis caused by meningococcus(600mg B.D
for 2 dayz) by H.influenza (600mg/day for 4 days)
• Rifampicin can also be used for prosthetic valve endocarditis.
40
40. 3. PYRAZINAMIDE(Z)-Nicotinamide analogue
Mechanism ofAction
PYRAZINAMIDE
Pyrazinoic acid (POA+)
Inhibit the mycolic acid Synthesize
Pyrazinamidase/Nicotinamidase
41
Enter M.tuberculosis
pncA
M/A : Similar to INH-– Cell wall synthesize
Action : Bactericidal
Highly effective in Acidic PH
Lethal to I/C organism & at inflammatory
site -
Best result is seen when used in initial phase
of therapy- Good sterilizing properties
Shorten duration of treatment & Decrease risk
of relapse : So pyrazinamide is added in first 2
initial months of therapy.
Resistance: mutation of pncA, only if used
alone.
41. • P/K:
• Good CSF distribution – useful for meningeal TB
• Dose: 25-30 mg/kg /day
Safe during pregnancy
• ADR:
• Hepatotoxicity (Dose related, C/I –liver disease)
• Hyperuricemia- gout can occur
• Abdominal distress, arthralgia, fever
• Cautious: DM- repeated blood sugar monitoring done.
42
42. 4. Ethambutol
M/A: Inhibition of mycobacterium cell wall synthesis- but target is different
Aarabinosyl transferase inhibition
Inhibit Arabinosyl transferase-Шenzyme –encoded by gene embA
Disrupt the transport of Arabinosesugar
Arbinogalactan biosynthesis impaired
Disruption in mycobacterial cell wall formation
Interreference of mycolic acid incorporation in to mycobacterial cell wall
43
Resistant:
mutation of embA
gene
43. Ethambutol
• Spectrum: M Tb, MAC
Tuberculostatic drug
Fast multiplying bacteria are more susceptible – added to triple drug
regimen hasten the rate of sputum conversion
44
44. • P/K:
• Metabolism: liver & kidney – Caution for patients have kidney disease
• ADR:
• Patient's acceptability is very good: low S/E
• Visual side effect: Dose/ Duration related side effect
• lose of visual acuity/ colour vision, retrobulbar neuritis leads – tubular vision
• Stop medicine- at first complain of impairing vision
• Children are contraindicated as they are unable to report
• Dose: 1000 mg OR 15mg/ kg OD
Safe in pregnancy
45
48. 2nd line antitubercular drugs(ATD)
Lower efficacy- weaker than 1st line ATD
Higher toxicity (even though good efficacy) –poor patient tolerability
Effective against Resistant organism - “M.TB resistant to first line
antitubercular drug”
Used in RESISTANANT TB : only when first line drug failed
Monitoring of ADR is must while using 2nd line ATD
Expensive
50. Bedaquiline
Grouping of ATD drugs according to hierarchy in efficacy and/ priority in use
Rifabutin,
Rifapentine
51. Description of individual group…
• M/A
• Action on type of mycobacteria (resistant/ atypical mycobacteria/
mycobacterium avium complex-MAC)
• Cross resistant
• Adverse effect profile and its monitoring
• Doses of individual drug
• Specific drug selection in group for “management of Resistant TB”
53. Group 2: Injectable drugs: Kanamycin & Amikacin
• M/A: Inhibit protein synthesis
• Spectrum of Action:
• Sensitive to
S resistant strain
MDR (R+H) strain of M.TB
• Resistant: Cross resistant
• ADR- Equally nephrotoxic but produces less
vetibulotoxicity than hearing loss.
Patient should be warned to report if
tinnitus or vertigo occur
Audiometry and RFT monitoring is must.
RNTCP prefer this drug
Kanamycin (Km)
More toxic but LESS
EXPENSIVE
750mg-1000mg/day
Amikacin(Am)
LESS TOXIC but
More expensive
Other country prefer
this drug
54. Capreomycin (Cm)/ – Alternative to aminoglycoside
• Polypeptide antibiotic- chemically differ from aminoglycoside
• Action: same- Mycobecteriocidal
Effective against Resistant to S / Am respond to Cm.
MDR (R+H)- TB
• ADR: Ototoxicity/ Nephrotoxicity
• parenteral administration- I/M- injection site pain, fever, Rash,
eosinophilia additional side effects.
• Used as ALTERNATIVE to aminoglycoside
HRZE
S
Am
Cm
56. 3. Fluroquinolones FQs (Mfx /Lfx /Ofx /Cfx)
• M/A: Inhibit DNA polymerase
• Action : Mycobactericidal
• FQ is best 2nd line drug because…….…
- Potent,
- Bactericidal,
- Orally active
- Sensitive to MAC, M. fortuitum ,
atypical mycobacterium
- Penetrate cell kill microorganism
inside macrophage as well
Well tolerated 2nd line ATD
GIT- abdominal
pain/nausea/
diarrhea
CNS- headache,
insomnia, dizziness,
Tremor, seizure
Hypersensitivity
reaction: rash,
pruritus,
photosensitivity
ADR -FQ
Q-T prolongation
M
M
57. • Most active is Mfx followed by Lfx – Ofx – Cfx
• Cfx- More active on Atypical mycobacteria
• Mfx: Most active but more CNS, CVS side effects
• Lfx: Good pharmacokinetic profile and less side effect
Lfx: Standardized regimen forMDR –
TB management by RNTCP (2016)
Dose: Mfx- 400mg,
Ofx- 800mg
Lfx- 1000mg
59. 4. Ethionamide(Eto) & 5. Proethinamide (Pto)
• Similar to INH, same mechanism (different gene Eto) but LOWER efficacy
• Action on Atypical mycobacteria and MAC
• Frequent ADR : POOR tolerability
Abdominal discomfort
Hepatitis
Peripheral neuritis- pyridoxin prophylaxis needed
Behavioral changes
Endocrinal disturbance
Goiter
So start with lower dose: 250mg/ day- 750mg/day
RNTCP- standardized regimen for
MDR-TB,
MAC infection in AIDS patients
Reserve drug for leprosy
60. 6. Cycloserine (Cs) & 7. Terizidone
• M/A: It is D-alanine analogue and hence it
replaces alanine which is essential for cell
wall synthesis.
• Bacteriostatic
Action on :
- H/R resistant MTB
- MAC
- Gram+Ve, Chlamydia, E.coli
• ADR : Neurological side effects
❶ ❷
62. 7. Terizidone
Two molecule of cycloserine
Same M/A and same antibacterial properties.
Less neurotoxic
A substitute of Cs especially in genitourinary TB as it attain higher and
sustained concentration into urine.
• Dose- 500-750mg/ day
63. 8. PAS- Paraaminosalicyalic acid
• Chemically similar to Sulfonamide
• M/A- Inhibit folate synthesize of MTB
• Action - Static- least active drug –but delays development of
resistant
• ADR:
• Poor acceptability – because
• ADR- GIT disturbance: anorexia, nausea ,epi pain
• Rashes, fever, malaise, Hypokalaemia , Liver damage, goitre
• Used as sodium salt (Na+ overload) and Ca salt (gastric
intolerance),
64. PAS ; Don’t add to efficacy to more active drug that are given with it
but it delays development of resistant.
MDR-TB Standard regimen only
Dose: 200mg/kg
10-20g/day in divided doses
When other 2nd line cidal drugs
(Km, Ofx, Z, Eto) or both static
(E, Cs) cant used.
65. 9. Rifabutin
• Action: More action on- MAC
• Resistant :Cross resistant to R- MDR-TB
• P/K: Weaker enzyme inducer-
• Use:
Treatment of MAC infection in HIV-AIDS
to avoid drug –drug interaction between
antiretroviral drug ( NNRTI,PI) +
antitubercular drug (R)
Prophylactic: Rifabutin- 300mg/ day or
Azithromycin/ clarithromycin
Treatment : Rifabutin is prescribed with 2-3
antiMAC antitubercular drugs.
Dose & ADR : similar to R
10. Rifapentine
Same M/A, spectrum, Potent enzyme
inducer/ drug- drug interaction /cross
resistant
P/K- longer t1/2 (13-15hr)
Only indication is it can be used in
continuation phase once or twice weekly
as rifampicin substitution of TB treatment
Not suitable for intensive therapy
Latent TB Rx : INH + Rifapentine – once
a week regimen
Rifampicin- Drug sensitive
TB RX
Rifabutin MAC infection in
HIV-TB RX
Rifapentine substitute of R in
continuation phase - Drug sensitive
TB RX
66. 10. Clofazimine
• Dye- Antileprosy drug
• M/A: Interfere with template function of DNA
Alteration of membrane structure
Disruption of mitochondrial electron chain
• Antiinflammatory property
• Spectrum: M. Lepre, resistant M. TB
• ADR: Gi uspet, Skin reaction , discoloration of hair and body secretion
• Avoided during pregnancy
• USE: DR tuberculosis: RR/ MDR TB
68. Bedaquiline (Bdq)
• USFDA approval in 2012 – SIRTURO, 2016 in India
• M/A : BDQ inhibit mycobacterial ATP synthetase – limiting
energy production
• Action: Bactericidal– Very low MIC – for MDR TB and XDR-TB strains : DS, MDR, PreXDR,
XDR strain of mycobacteria, M.Leprae
• Resistant – Mutation of ATP synthetase enzyme and efflux
NO cross resistant to any 1st /2nd line ATD
• P/K- CYP3A4- drug inhibitor/ inducer- drug drug interaction
• ADR: Nausea , headache, arthralgia, QT prolongation, hepatotoxicity.
69. Week 0–2: BDQ 400 mg (4 tablets of 100 mg) daily (7 days per week)
Week 3–24 BDQ 200 mg (2 tablets of 100 mg) 3 times per week (with at least 48 hours
between doses) for a total dose of 600 mg per week
• USFDA approval in 2012 – SIRTURO, India in 2016 -RNTCP introduced BDQ at
selected centres through “conditional access programme”
• Indication/ Recommendation :
Rx of only pulmonary MDR TB adult (>18yrs) when no optimum regimen
constructed.
Use in combination with 3-4 (Sensitive) anti TB drugs for maximum 24week.
Each tablet should be taken with meal.
Must NOT used for DS-TB OR Extrapulmonary TB, nontubercular mycobacterial
Women receiving BDQ should be nonpregnant.
Dose:
70. Pretomaind
• Bicyclic nitroimidazole- Prodrug
• USFDA 2019- highly resistant TB
• M/A: Inhibit cell wall synthesize, depetion of ATP- direct cell
toxicity
• Act on I/C, Persisters
• Resistant: fgd gene- drug activation
• Dose: 200mg OD
• Use: in Resistant TB only
• ADR: GI upset, headache. QT prolongation
• Pregnancy:?????
71
71. Delamanid
• Prodrug- same as pretomanid
• Gene involved: fgd 1 and fbi A
• Safest and most effective drug for MDR TB patients
• ADR: GI Upset, headache, QT prolongation
• Resistant: mutation to fgd1 and fbi A
• Dose: 100mg BD -24week with OBR (Optimized background
regimen)
• Only used with “ Compansate use” after prior approval form DCGI.
72
72. General criteria for using newer drugs ( Bdq, Dlm)
• Patients of MDR- TB/ RR TB > 6years as follows
age >18yrs : Bdq and Dlm can be given
Dlm can be given to children and adolescenc aged 6-17years
Approval from DCGI required for using Bdq and Dlm for age 3-
6years
Nonpregnant female/ postmenopausal/ on non hormonal contraceptive:
can be used for 2 yrs
Patient with stable arrythmia only after cardiac check up
Exclusion: Pregnancy and lactation, arrhythmia
73
74. 1. Aminoglycoside- Km/ Am- Oto/ nephrotoxicity , S Resistant strain/ MDR TB, Km – used
in RNTCP- MDR –TB Mx
2. Cm- : Alternative to aminoglycoside , used when S/Am resistant
3. FQ (Mfx –Lfx- Ofx- Cfx): Best 2nd line oral drug – effective against MDR / Atypical myco/
MAC- well tolerable, Lfx in MDR TB Mx regimen by RNTCP.
4. Eto/ 5. Pto : INH similar – poor tolerable-GIT/PN/CNS/Endo- use : RNTCP-MDR TB
/MAC infection
6. Cs: D alanine analogue – Static -slow resistant development- NO Cross resistant-
Neurological ADR- use : Mx -RNTCP-MDR TB
7. Terizidone: Less neurological ADR- genitourinary TB
8. PAS: similar to Sulfa drug- Static- Poor tolerable (GIT/hypokelemia/goitre/liver damage),
used when resistant to this drugs (4 cidal+ 2 static -Km, Ofx, Z, Eto, E, Cs) or cant be used.
75. 9. Rifabutin: less d-d interaction- replace Rifampin in Rx of MAC infection in HIV
patients
10. Rifapentine-long t1/2- substitute of rifampin –used continuous phase- once or
twice weekly instead of daily regimen.
11. BDQ: Only in selected cases of MDR TB, XDR- QT prolongation, hepatotoxicity
MDR –TB
Km
Lfx
Eto
Cs
MAC
Cp/Lfx
Rifabutin