1. ANTI-TUBERCULAR DRUGS
Presented by –
Dr.Sushrut Varun Satpathy
3 rd year PG
Deptt.of Pharmacology,SMIMS
Moderator –
Dr.Supratim Datta
Assoc.Prof.
Deptt. Of pharmacology

2. • CHRONIC GRANULOMATOUS DISEASE
• MAJOR HEALTH PROBLEM ( DEVELOPING
COUNTRIES)
• 1/3RD OF WORLD’S POPULATION INFECTED
WITH MYCO. TUBERCULOSIS
• 9.4 MILLION ACTIVE TB CASES GLOBALLY ( 2.3
MILLION CASES – INDIA – HIGHEST
CONTRIBUTOR)-WHO-2010
• G.O.I 2012 DECLARED TB – NOTIFIABLE
DISEASE

3. EVERY DAY IN INDIA ,
More than 900 people die of
TB
( ~ 2 deaths every 3 minutes )

4.  CONTROL AND TREATMENT OF TB –COVERED
UNDER NATIONAL PROGRAMME (RNTCP)
 Goal of RNTCP –
Decrease mortality and morbidity due to TB
Cut transmission of infection until TB cases ceases to be
major public health problem – detecting and curing
sputum smear positive patients
Achieve and maintain a cure rate of atleast 85% among
new sputum smear (+) and maintain detection of atleast
70%
Only effective means to achieve the goal of RNTCP is
the application of DOTS strategy

5. Components of DOTS – systematic strategy
having 5 components
 Political and administrative commitment
 Good quality diagnosis, primarily by sputum smear
microscopy
 Uninterrupted supply of good quality drugs
 Directly observed treatment (DOT)
 Systematic monitoring and accountability

6. Diagnosis of tuberculosis
 Identification of TB suspects –
m/c symptom –
Persistent cough , usually with expectoration
Others – weight loss , tiredness , fever with evening
rise , night sweats , chest pain , shortness of breath ,
anorexia and haemoptysis

7.  Sites of
extra-pulmonary
tuberculosis

8. A pulmonary TB suspect is defined as :
 An individual having a cough of 2 weeks or more
 Contacts of smear positive TB pts having cough of
any duration
 Suspected/confirmed extra-pulmonary TB having
cough of any duration
 HIV pts having cough of any duration

9.  1specimen (+) out of 2 - smear positive TB
 Smear (+) TB is further classified as new or re-
treatment cases based on their previous treatment
history
 Both specimens are smear (-) - prescribed
symptomatic treatment and broad spectrum anti-
biotics as Co-trimoxazole for 10-14 days
 Antibiotics such as FQs ( ciprofloxacin, ofloxacin,
levofloxacin etc), rifampicin or streptomycin, which
are active against TB , should never be used

10. According to clinical utility – Anti-TB drugs
can be divided into first line and second line
 First line drugs –
1. ISONIAZID (H)
2. RIFAMPIN (R)
3. PYRAZINAMIDE (Z)
4. ETHAMBUTOL (E)
5. STREPTOMYCIN (S)
 Second line drugs –
 Ethionamide (Eto)
 Prothionamide (Pto)
 Cycloserine (Cs)
 Terizidone (Trd)
 Para-Amino salicylic acid (PAS)
 Rifabutin
 Thiacetazone (Thz)
 FLUOROQUINOLONES
 Ofloxacin (Ofx)
 Levofloxacin (Lvx)
 Moxifloxacin (Mfx)
 Ciprofloxacin (Cfx)
INJECTABLE DRUGS –
 Kanamycin (Km)
 Amikacin (Am)
 Capreomycin(Cm)

11. Alternative grouping of Anti-tubercular
drugs
GROUP 1 First line oral anti-TB drugs Isoniazid,Rifampin,Pyrazina
mide,Ethambutol
GROUP 2 Injectable anti-TB drugs Streptomycin , Kanamycin,
Amikacin,Capreomycin
GROUP 3 Fluoroquinolones Ofloxacin,Levofloxacin,Moxi
floxacin,Ciprofloxacin
GROUP 4 Second line oral anti-TB drugs Ethionamide
,Prothionamide,Cycloserine,
Terizidone,PAS
GROUP 5 Drugs with unclear efficacy Thiacetazone,
Clarithromycin,
Clofazimine,Linezolid,Amoxi
cillin/clavulanate,Imipenem/
cilastatin

12. • Adopted from : treatment of tuberculosis guidelines ;
WHO, Fourth edition(2010) and RNTCP, DOTS-plus
Guidelines 2010
• Not recommended by WHO for routine use in MDR-TB
patients
Group 1 – are the most potent and best tolerated oral drugs
used routinely
Group 2 – potent and bactericidal , but injectable drugs
Group 3 – include FQs which are well tolerated bactericidal
oral drugs ; all patients with drug resistant TB should
receive one FQ
Group 4 – less effective, bacteriostatic/more toxic oral
drugs for resistant TB
Group 5 – drugs with uncertain efficacy; not recommended
for MDR-TB; may be used in XDR-TB

13. Isoniazid
(Isonicotinic acid hydrazide, H)
Primarily tuberculocidal
Fast multiplying are rapidly killed , but quiescent ones
are only inhibited
Acts on extracellular as well as on intracellular TB
Equally active in acidic or alkaline pH
One of the cheapest anti-tubercular drugs

14. Mechanism of Action -
Inhibition of synthesis of mycolic acids
Two gene products labelled ‘InhA’ and ‘ KasA’ , which
function in mycolic acid synthesis are targets of INH
action
INH enters sensitive mycobacteria which convert it by
a catalase-peroxidase enzyme into a reactive
metabolite
then forms adduct with NAD that inhibits InhA and
KasA

15. INH enters bacilli by passive diffusion
Drug is not directly toxic to the bacillus but must be
activated to its toxic form within the bacillus by KatG
(multifunctionary , catalase –peroxidase)
KatG catalyzes the production from INH of an
isoNicotinoyl radical that subsequently interacts with
mycobacterial NAD and NADP to produce a dozen
adducts

16. A nicotinoyl-NAD isomer, inhibits the activities of enoyl
acyl carrier protein reductase (InhA) and β-ketoacyl
acyl carrier protein synthase (KasA)
Inhibition of these enzymes inhibits synthesis of
mycolic acid -- bacterial cell death
Another Adduct, a nicotinoyl-NADP isomer , potently
inhibits mycobacterial DHFRase ,thereby interfering
with nucleic acid synthesis

18. Other products of KatG activation of INH include
superoxide,H2O2 , alkyl hydroperoxides and NO
radical may also contribute to INH bactericidal effect

19. Resistance of INH
About 1 in 106 tubercle bacilli is inherently resistant to
clinically attained INH concentration
If INH given alone , such bacteria will proliferate
selectively and after 2-3 months , an apparently
resistant infection appears
M/C mechanism which confers HIGH level resistance
– mutation of KatG (single point mutations in heme
binding catalytic domain of KatG , serine to
asparagine change at position 315)
INH resistance may also involve mutation in InhA and
KasA genes
Resistance due to efflux is also possible

20.  Combined with other drugs ,INH has good resistance
preventing action . No cross resistance with other
anti-tubercular drugs occurs ???? (KD tripathi 7th
edition ;767)
 Overexpression of of the genes for InhA – confers
low level resistance to INH and some cross-
resistance to ethionamide
 KatG 315 mutants have a high probablity of co-
occurrence with ethambutol resistance
 Mutation in KatG, ahpC, and inhA have also been
associated with rpoB mutations

21. Absorption , Distribution and Excretion
Bioavailability of oral isoniazid is ~ 100% for 300 mg
dose
INH is completely absorbed orally and penetrates all
body tissues , tubercular cavities, placenta and
meninges
Extensively metabolized in liver
Most important pathway being N-acetylation by NAT2
Acetylated pathway is excreted in urine
Rate of acetylation shows genetic variation

22.  Fast acetylators (30 – 40% of indians)
T1/2 of INH 1 Hr
 Slow acetylators (60 – 70% of indians )
T1/2 of INH 3 Hr
 Acetylator status does not matter if INH is
taken daily,but biweekly regimes are less
effective in fast acetylators
 INH induced peripheral neuritis > common in
slow acetylators
 A hepatotoxic minor metabolite is produced by
CYP2E1 from acetylhydrazine

23. Interactions
 Aluminium hydroxide inhibits INH absorption
 INH retards phenytoin , carbamazepine, diazepam,
theophylline and warfarin metabolism by inhibiting
CYP2C19 and CYP3A4
 Since rifampin is an enzyme inducer, its concurrent
use counteracts the inhibitory effect of INH
 PAS inhibits INH metabolism and prolongs its T1/2

24. Drug Daily dose
Mg/kg maximum
3 times per week dose
Mg/kg Daily
Max
ISONIAZID (H) 5 (4-6) 300 10(8-12) 900 mg

25. Adverse effects
 Well tolerated
 Peripheral neuritis and a variety of neurological
manifestations ( paresthesias , numbness , mental
disturbances , mental disturbances , rarely convulsions )
– dose dependent toxic effects
 Interference with the production of the active co-enzyme
pyridoxal phosphate from pyridoxine -- increased
excretion in urine – pyridoxine given prophylactically (10
mg/dl)
 INH neurotoxicity is treated by pyridoxine 100 mg/day
 Hepatotoxicity ( rare in children ), but more common in
older people and in alcoholics ( chronic alcoholism
induces CYP2E1 – generates the hepatotoxic metabolite
)

26. Rifampin (Rifampicin , R)
 Semisynthetic derivative of Rifamycin B obtained from
streptomyces mediterranei
 Bactericidal to M. Tuberculosis and many other gram(+)
and gram (-) bacteria like staph.aureus , N.meningitidis,
H.influenza, E.coli,Kleibsella , Pseudomonas,Proteus and
legionella
 Against TB bacilli , it is as efficacious as INH and better
than all other drugs
 Bactericidal actions covers all subpopulations of TB
bacilli , but acts best on slowly or intermittenly dividing
ones (spurters)
 Both extra and intracellular organisms are affected

27. Mechanism of action -
 Interrupts RNA synthesis by binding to β subunit of
mycobacterial DNA dependent RNA polymerase
(encoded by rpoB gene )

28. RESISTANCE –
 Prevalence of rifampin-resistant isolates are 1 in
every 107 to 10 8 bacilli
 Rifampin resistance is nearly always due to mutation
in the rpoB gene reducing its affinity for the drug
( In 86% cases due to mutations at codons 526 and
531 of rpoB gene)
 No cross resistance with any other anti-tubercular
drug, except rifampin congeners
 Rifampin monoresistance occurs at a higher rates
when pts with AIDS and multi-cavitary TB are treated
with either rifapentine or rifabutine

29. Pharmacokinetics -
 Well absorbed orally
 Bioavailability ~ 70% , food decreases absorption
 Rifampin is to be taken in empty stomach
 Widely distributed in the body;
 penetrates intracellularly , enters tubercular cavities,
caseous masses and placenta
 It crosses meninges , largely pumped out of CNS by P–
glycoprotein
 Metabolized in liver – active deacetylated metabolite –
excreted mainly in Bile , some in urine
 Rifampin and its deacetylated metabolite undergoes
enterohepatic circulation
 T1/2 – 2-5 hrs

30. Interactions
 Rifampicin is a microsomal enzyme inducer – increases
several CYP450 isoenzymes – CYP3A4 , CYP2D6,
CYP1A2 , CYP2C subfamily
 Enhances its own metabolism ( area under the plasma
concentration-time curve is reduced by ~ 35%) as well as
that of many drugs including warfarin , oral
contraceptives, corticosteroids, sulfonylureas,
corticosteroids, HIV protease inhibitors, NNRTIs ,
theophylline, metoprolol, fluconazole,ketoconazole,
clarithromycin, phenytoin etc
 Contraceptives failure have occurred – advisable to
switch over to an OCP containing higher dose ( 50 µg ) of
estrogen or alternative method of contraception

31. Adverse effects -
 Incidence of adverse effects is similar to INH
 Hepatitis , a major adverse effect, generally occurs in
pts with pre-existing liver disease and is dose related
 Jaundice – discontinuation of drug – reversible
 Minors reactions , not requiring drug withdrawal and
more common with intermittent regimes
 Cutaneous syndrome :
 Flu syndrome :
 Abdominal syndrome :
 Urine and secretions may become orange-red but
this is harmless

32. Other uses of rifampin
1. Leprosy
2. Prophylaxis of Meningococcal and H.influenza
meningitis and carrier state
3. Second/third choice drug for MRSA, Diptheroids
and legionella infections
4. Combination of doxycycline and rifampin is first line
therapy of brucellosis

33. Pyrazinamide (Z)
 Chemically similar to INH – Pyrazinamide was
developed parallel to it (1952)
 Weakly tuberculocidal
 more active in acidic medium and slowly replicating
bacteria
 More lethal to intracellular bacilli and at sites
showing inflammatory response
 Highly effective during the first 2 months of therapy
when inflammatory changes are present
 Inclusion enabled duration of treatment to be
shortened and risk of relapse to be reduced

34.  M.O.A – not well established
Similar to INH – converted inside mycobacterial into
active metabolite pyrazinoic acid by pyrazinamidase
encoded by pncA gene
Gets accumulated in acidic medium and probably
inhibits mycolic acid synthesis, but by interacting
with a different fatty acid synthase
Pyrazinoic acid also appears to disrupt mycobacterial
cell membrane and its transport function
Resistance to Z develops rapidly if it is used alone,
and is mostly due to mutation in the pncA gene

35.  Absorbed orally
 Widely distributed , good penetration in CSF
 Extensively metabolized in liver and excreted in
urine
 Plasma T1/2 ~ 6 hrs
 Adverse effects –
1. Hepatotoxicity
2. Hyperuricaemia
3. Others – abdominal distress
non-gouty arthralgia
fever

36. Ethambutol (E)
 Selectively Tuberculostatic
 Active against MAC as well as some other
mycobacteria
 Fast multiplying bacilli – more susceptible
 Added to triple regime of RHZ – hastens the rate of
sputum conversion and prevents development of
resistance
M.O.A –
 Inhibits arabinosyl transferases (encoded by embAB
genes) involved in arbinogalactan synthesis
interfering mycolic acid incorporation in
mycobacterial cell wall

37.  Resistance to E develops slowly
 Most commonly associated with mutation in embB
gene ,
 About 3/4th of oral dose is absorbed
 Distributed widely , but penetrates meninges
incompletely and is temporarily stored in RBCs
 Excreted in urine by GFR and tubular secretion
 Plasma T1/2 ~ 4 hrs

38. ADVERSE EFFECTS -
1. Dose dependent and reversible visual disturbances
like Optic Neuritis - reduced visual acuity , central
scotoma and loss of ability to see Green, less
commonly Red - ? Due to its effect on Amacrine
and bipolar cells of retina ^
2. Hyperuricemia
3. Peripheral neuritis

39. Streptomycin
 First clinically useful anti-TB drug
 Tuberculocidal but less effective than INH or rifampin
 Acts only on extracellular bacilli – poor penetration
 Penterates tubercular cavities , but does not cross to
CSF
 Poor action in acidic medium
 Not absorbed orally , must be administerd by IM inj.
 T1/2 is prolonged in renal failure
 NOT HEPATOTOXIC
 Use restricted to max. of 2 months- labelled as
‘supplemental’ 1st line drug !

40. Other drugs -
 Thiacetazone – tuberculostatic drug. Major A/E –
hepatitis , bone marrow suppression and steven johnson
syndrome ( not used in HIV pys due to risk of severe
hypersensitivity reactions including exfoliative dermatitis)
 PAS related to sulfonamides , acts by similar mechanism
–bacteriostatic
 Ethionamide/prothionamide – tuberculostatic –hepatitis
, optic neuritis and hypothyroidism , can also be used in
leprosy ^
 Cycloserine is a cell wall synthesis inhibiting drug and
can cause neuropsychiatric adverse effects

41.  Kanamycin and Amikacin are injectable
aminoglycosides – used in treatment of MDR TB
 Capreomycin – injectable polypeptide – ototoxicity ,
nephrotoxicity ,hypokalemia and hypomagnesemia
 FQs – Ofloxacin , Moxifloxacin and Levofloxacin -
effective against MAC in AIDS patients
 Newer macrolides like Azithromycin and
Clarithromycin against non-tubercular atypical
mycobacteria

42.  Rifabutin more effective than Rifampicin against
MAC , longer T1/2 ~ 45 hrs , less potential than
rifampicin to induce microsomal enzymes and thus ,
prefered in pts on anti-HIV drugs ( protease
inhibitors or NNRTIs mainly nevirapine )
commonly causes – GI discomfort
Anterior Uveitis, Hepatitis,
clostridium associated diarrhoea , diffuse
polymyalgia syndrome , yellow skin discoloration
 Rifapentine – similar to rifampicin but more lipophillic
and longer acting . Not approved for adm. to HIV pts
because of higher rate of relapse

43. Treatment of Tuberculosis -
 Combination chemotherapy ( short course
chemotherapy) – to prevent the emergence of
resistance to any 1drug
 For treatment purpose , previously treated patients
were divided into three categories . Under RNTCP
2010 guidelines , only two categories are
distinguished
 Category 1 – new pts who have not been exposed
to anti-tubercular agents earlier ( previous category
1 as well as 3 cases)
 Category 2 – old cases who have been exposed to
anti-tubercular drugs earlier ( treatment defaulters
and relapse cases)

44. First line agents

45. New patient ( category 1)
 Initial treatment with 4 drugs (HRZE) including 3
bactericidal drugs reduces the risk of selecting
resistant bacilli ^
 After intensive phase – few bacilli left – only 2 highly
effective cidal drugs in the continuation phase
 Extension of intensive phase beyond 2 months is not
recommended now . However , In such cases ,
authorities recommend 9 month treatment instead of
6 month ?? ( KD Tripathi 7th ed. ;2013: 774-775 )

46. RNTCP guideline -
 If the sputum smear is positive after 2 months of
treatment , the intensive phase of four drugs (HRZE)
are continued for another 1 month
sputum examined after completion of extension of
intensive phase
irrespective of the results – 4 months of continuation
phase is started
If sputum smear postitve after 5 or more months of
treatment – “ failure”- placed on “previously
treated” and sputum sent ( C & DST)

47.  While treating TB meningitis( NEW pts) ,
Streptomycin is used in place of ethambutol during
the intensive phase ( H3R3Z3S3 instead of H3R3Z3E3)
 Continuation phase of treatment with TBM or spinal
TB is for 7 months – total duration is for 9 months
 In areas with high level of primary (H) resistance –
WHO suggests inclusion of (E) along with (H+R) in
continuation phase

48. Previously treated ( Category 2)
 For TB pts who have had more than one month anti-
TB treatment previously
 Higher risk of having drug resistance
 5 drugs are prescribed in the intensive phase and
total duration of treatment is 8 months
 Relapses , Treatment after default , Failures and
others are treated with this regime
 Regimen is 2 S3H3R3Z3E3 /1 H3R3Z3E3 /5 H3R3E3

49. Intensive phase consists of 2 months of HRZES
followed by 1 month of HRZE, all given under direct
observation thrice a week on alternate days
Pts subjected for follow up sputum examination at the
end of 3 months
If sputum smear (+) at the end of 3 months of
treatment , intensive phase drugs (HRZE) are
extended for another
Irrespective of sputum results at the end extended
intensive phase , 5 months of continuation phase is
started
If the sputum remains positive at the end of extended
intensive phase, sputum is sent to accredited C &

50. MultiDrug-Resistant (MDR) TB
 Defined as resistance to both H and R , and may be any
number of other (1st line) drug
 MDR –TB has a more rapid course with worse outcomes
IDENTIFICATION OF MDR – TB SUSPECTS –
Following are the criteria to label a patient as MDR-TB
suspect –
A new smear (+) pt. remaining smear (+) at end of 5th
month
A new smear (-) pt. becoming smear (+) at the end of 5th
month
A pt. treated with regimen for previously treated remaining
(+) at fourth month
Smear-positive contacts of an established / confirmed
MDR-TB case

51. Diagnosis of MDR-TB
 Diagnosis of MDR-TB should be done through C &
DST from a quality assured lab
 On being diagnosed as MDR-TB case- Pt. referred
to a designated state level DOTS-plus site
 Specialized centers limited in number , atleast one
such center is expected to be in each state with
ready access to an C & DST
 DOTS-plus site- supported by qualified staff
available to manage pts. using second line RNTCP
MDR-TB regimen

52. RNTCP MDR-TB treatment regimen -
 RNTCP is using a standardised treatment regimen
(STR) , comprising of 6 drugs ( kanamycin (Km),
levofloxacin(lvx), ethionamide (Eto), pyrazinamide
(Z), ethambutol (E) and cycloserine (Cs)
 Dosages of drugs are based upon 3 weight bands

53. Drug 16-25 kg 26-45 kg > 45 kg
Km 500 mg 500 mg 750 mg
LVX 200 mg 500 mg 750 mg
Eto 375 mg 500 mg 750 mg
E 400 mg 800 mg 1000 mg
Z 500 mg 1250 mg 1500 mg
Cs 250 mg 500 mg 750 mg
PAS 5 g 10 g 12 g
Pyridoxine 50 mg 100 mg 100 mg

54.  All drug given in a single daily dosage under DOT by
a DOT provider
 All pts. will receive drugs under direct supervision on
6 days of the week
 On the 7th day (Sunday) , oral drugs will be
administered unsupervised and kanamycin will be
omitted
 If intolerance occurs to drugs , ethionamide ,
cycloserine and PAS may be split into two dosages
and the morning dose adm. under DOT and evening
subsequently self-administered
 Empty blister packs of self-administered doses will
be checked the next morning during DOT

55.  100 mg of pyridoxine is adm. to all pts under RNTCP
MDR-TB regimen
 If pts gain atleast 5 kgs of weight during treatment and
crosses the weight band range , DTS-plus site committee
may consider moving the patient to the higher weight
band drug dosages ^
DURATION OF TREATMENT -
IP – atleast 6 months
Extended up to 7/8/9th months in pts who have (+) culture
result taken in 4/5/6th months of treatment
correspondingly
Continuation phase is given for 18 months following IP

56. Follow up schedule -
 Smear examination should be conducted monthly
during IP and atleast quaterly during the CP
 Culture examinations should be done atleast 4, 6,12,
18 and 24 months of treatment

57. Guidelines fro treatment of MDR + XDR TB
1. Use minimum 4 drugs ( 6 drugs in extensive phase
)
2. Follow the hierarchy of drugs from class 1 through
class 5 as follows :
a. Use any first line oral agent that may be effective
b. Use injectable agent to which strain is susceptible
c. Use a later generation FQ
d. Use second line oral drugs to which the patient is
not exposed previously
e. Use drugs with unclear efficacy

58. Class 1 First line oral drugs H,R,Z,E
Class 2 Injectable agents Streptomycin,
Kanamycin, Amikacin,
Capreomycin
Class 3 Fluoroquinolones Levofloxacin ,
Moxifloxacin
Class 4 Oral Bacteriostatic PAS, Cycloserine ,
Ethionamide
Class 5 Drugs with uncertain
efficacy
Linezolide , Clofazimine ,
Amoxicillin + clavulanate
, Clarithromycin
,Imipenem/cilastatin,
Thiacetazone , high dose
Isoniazid

59.  For example if bacteria is resistant to H and R only,
the treatment will be 6 ZE + FQ + One injectable +
PAS + Cycloserine in the extensive phase
 18E + FQ + PAS + Cycloserine in the continuation
phase
 Injectable drugs and Z is removed and rest 4 drugs
are continued for minimum 18 months in
continuation phase

60. Extensively drug resistant TB
 MDR-TB cases that are also resistant to FQs as well one
of the injectable 2nd line drugs and may be any number
of other drugs
 Bacilli are resistant to atleast 4 most effective cidal drugs
viz. H,R,FQ and one of Km/Am/Cm
 XDR-TB- very difficult to treat - rapid course and high
mortality
 To prevent further amplification of resistance –
standardized MDR regimen ( category 4 treatment) must
be immediately stopped
 Expert panel may decide on instituting category 5
treatment , including group 5 drugs – uncertain efficacy
and expensive
 New drugs like PA-824 and TMC-207 is also being

61. Tuberculosis in Pregnant Women -
 H,R,E and Z safe to the foetus and recommends the
standard 6 month (2HRZE + 4 HR)- WHO and
British Thoracic Society
 S is C/I - ototoxic
 Z not recommended in US – lack of adequate
teratogenecity data
 In India – advisable to avoid Z and to treat pregnant
TB pts in India – 2 HRE + 7 HR ( total 9 months)
 All pregnant women treated with INH should receive
Pyridoxine 10-25 mg/day

62. Role of Corticosteroids -
 Tb is a relative C/I for use of glucocorticoids . However in
certain situations , Glucocorticoids may be used under
the cover of effective Anti-TB therapy –
1. Tuberculosis of serous membranes like pleura ,
pericardium , meninges etc. to prevent fibrous tissue
formation and its sequelae
2. To treat hypersensitvity reactions to antitubercular
drugs
3. Tuberculosis of the eye , larynx , genitourinary tract to
prevent fibrosis and scar tissue formation
Prednisolone is a preferred agent except in meningitis (
dexamethasone is preferred)
Steroids C/I in intestinal TB – risk of perforation

63. Atypical Mycobacterial Infections -
 Clarithromycin or Azithromycin is recommended for
prophylaxis of Mycobacterium Avium Complex
(MAC) in pts with CD4 count < 50 µl
 Treatment of MAC requires REC regimen ( Rifabutin
+ Ethambutol + Clarithromycin/Azithromycin
 Due to its long T1/2 , Azithromycin can be used as
once weekly dose in place of one daily dose of
Clarithromycin for prophylaxis of MAC
 Other drugs effective against atypical mycobacteria
are quinolones ( ciprofloxacin , levofloxacin ,
moxifloxacin and gatifloxacin) and Amikacin

64. Treatment regimen of MAC infection -
 Intensive phase
1. Clarithromycin 500 mg BD or Azithromycin 500 mg OD
2. Ethambutol 1000 mg/day (15 mg/kg) depends
on
3. Rifabutin 300 mg/day the
response
± till CD4 >100
Ciprofloxacin 500 mg BD and
sympt.relief
or Levofloxacin 500 mg OD ( 2- 6 months)
or Moxifloxacin 400 mg OD
 Maintenance phase
1. Clarithromycin /azithromycin

65. THANK YOU FOR YOUR
PATIENCE !!
HAVE A GREAT DAY !