Anti Mycobacterial Drugs

• Mycobacteria are rod-shaped aerobic bacilli that
multiple slowly, every 18 to 24 hours.
• Their cell walls contain mycolic acids, which give

its name.
• Mycobacterium tuberculosis can cause the active

disease known as tuberculosis (TB) and
• latent tuberculosis infection (LTBI)
• TB is the leading infectious cause of death
worldwide, and over 2 billion people already
have been infected.
• Other species include M. avium,M. abscessus,

M. leprae and others.
• TB treatment generally includes four f irst-line
drugs.
• Second-line drugs are typically less effective,

more toxic, and less extensively studied.
• They are used for patients who cannot tolerate

the first-line drugs or have resistant TB.
First-line drugs :
1. Isoniazid (INH),
2. Rifampin,
3. Pyrazinamide,
4. Ethambutol
• Active disease always requires treatment with

multidrug regimens, and preferably three or
more drugs

• Standard short-course chemotherapy for
tuberculosis includes :
• (the intensive phase):isoniazid, rifampin,

ethambutol, and pyrazinamide for 2 months
followed by:
• (the continuation phase) isoniazid and rifampin for
4 months.
• The intensive phase can be prolonged to 6 months

followed by continuation phase of 3 months
• Second line regimens for MDR-TB.
• aminoglycoside
• a fluoroquinolone
• any first-line drugs that remain active, and
• one or more of the following: cycloserine, ethionamide,
or p-aminosalicylic acid.
• For extensively drug resistant TB (XDR-TB)
• clofazimine,
• linezolid
• One successful strategy for achieving better
treatment completion rates is directly observed
therapy, also known as DOT.
• Patients take their medications while being

watched by a member of the health care team.
• DOT has been shown to decrease drug resistance
and to improve cure rates.
• Most public health departments offer DOT

services.
• It has broader antimicrobial activity than
isoniazid .
• Because resistant strains rapidly emerge during

monotherapy, it is never given as a single agent
in the treatment of active tuberculosis.
Rifampin binds to the β subunit of
bacterial DNA–dependent RNA
polymerase and thereby inhibits
RNA synthesis.
Resistance to rifampin can be caused:
By a mutation in the af finity of the bacterial DNA-

dependent RNA polymerase for the drug.
By decreased permeability
• Rifampin is well absorbed after oral administration.
• It is excreted mainly through the liver into bile.
• Rifampin is distributed widely in body fluids and tissues.
• Rifampin is relatively highly protein bound and adequate CSF
concentrations are achieved only in the presence of meningeal
inflammation.
• Rifampin can induce hepatic cytochrome P450 enzymes and
transporters , leading to numerous drug interactions.
Rifabutin a derivative of rifampin, is preferred for
TB patients coinfected with the hum an
immunodeficiency virus (HIV).
Rifabutin is a less potent inducer (approximately

40% less) of cytochrome P450 enzymes, thus
lessening certain drug interactions.
Refapentine. has activity greater than that of

rifampin and it also has a longer half-life.
It is used in latent TB infection.

1.Mycobacterial infections:
Rifampin usually600mg/day, 10mg/kg/day,

Orally must be administered with isoniazid
or other first line antituberculous drugs to patients
with active tuberculosis to prevent emergence of
drug resistant mycobacteria.
2. Atypical mycobacterial infections.
3. Leprosy.
4. As alternative of isoniazid in prophylaxis of
latent tuberculosis 600mg/day as a single agent
for 4 months.
5. It i s used prophyl acti cal l y for i ndi vi dual s
exposed to meningitis caused by meningococci
or Haemophilus inf l uenzae. 600mg, twice daily,
for 2 days.
6. 6.Osteomyelitis and prosthetic valve
endoca rdi t i s ca u sed by st a ph y l ococci i n
combination therapy with other agent
1. Rifampinimparts a harmless orange color to
urine, sweat and tears .
1. About 20% drug excreted in feces and 50% in
urine in unchanged form.
1. Ethambutol crosses the blood brain barrier only

if the meninges are inflammed.
1. Ethambutol accumulates in renal failure and the

dose shoul d be reduced to ha l f i n rena l
impairment.
Tuberculosis:
1. E t h a m b u t o l h y d r o c h l o r i d e 1 5
-25mg/kg/d is usually given as a single
daily dose in combination with
isoniazid or rifampin.
1. Optic neuritis resulting in loss of visual
acuity and red green color blindness.
Usually occur at doses of 25mg/kg/day
continued for several months.
2. Ototoxicity
3. Nephrotoxicity
Toxicity is dose related and the risk is increased in
elderly
• Pyrazinamide is well absorbed from GIT.
• It is widely distributed in body tissues,
including inflammed meninges.
• The half life is 8-11 hours.
• It is metabolized by the liver, but metabolites
are renally cleared.
Pyrazinamide is an important front line drug
used in conjuction with isoniazid & rifampin in
short course (i.e 6 months) regimens.
1. Hyperuricaemia (it may provoke acute gouty
arthritis).
2. Hepatotoxicity (in 1-5% of patients-major
adverse effect).
3. Nausea, vomiting, & drug fever.

Anti Mycobacterial Drugs

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• Mycobacteria are rod-shaped aerobic bacilli that

multiple slowly, every 18 to 24 hours.

• Their cell walls contain mycolic acids, which give

• Mycobacterium tuberculosis can cause the active

• Other species include M. avium,M. abscessus,

• Second-line drugs are typically less effective,

• They are used for patients who cannot tolerate

• Active disease always requires treatment with

• (the intensive phase):isoniazid, rifampin,

• The intensive phase can be prolonged to 6 months

• For extensively drug resistant TB (XDR-TB)

• Patients take their medications while being

• Most public health departments offer DOT

• Because resistant strains rapidly emerge during

By a mutation in the af finity of the bacterial DNA-

Rifabutin is a less potent inducer (approximately

Refapentine. has activity greater than that of

It is used in latent TB infection.

Rifampin usually600mg/day, 10mg/kg/day,

1. Ethambutol crosses the blood brain barrier only

1. Ethambutol accumulates in renal failure and the

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