Treatment Options for Mycobacterial

Infections
Isoniazid
Mechanism of action
Isoniazid inhibits synthesis of mycolic acids, essential components
of mycobacterial cell walls.
Pharmacokinetics
Isoniazid diffuses throughout total body water, even the central
nervous system. Metabolism of isoniazid occurs by acetylation.
In patients who are genetically fast acetylators,
isoniazid may not reach therapeutic levels and will have a
short plasma t compared with that of slow acetylators.
Slow acetylators are at a greater risk for drug-related toxicities
because of the drugs long t.
Clinical use
At therapeutic levels, isoniazid is bactericidal against actively
growing intracellular and extracellular Mycobacterium tuberculosis;
therefore the drug is primarily used in treatment or
prophylaxis of tuberculosis.
Adverse effects
Neuropathies may occur with isoniazid as a result of pyridoxine
(vitamin B6) deficiency, but supplementation with vitamin
B6 often prevents or minimizes this. Severe, even fatal, hepatitis
may occur, and patients should avoid taking acetaminophen
or drinking alcohol when taking isoniazid.

Rifampin
Mechanism of action
Rifampin inhibits bacterial RNA polymerase, which prevents
transcription by suppressing initiation of RNAchain formation.
Pharmacokinetics
Rifampin is a potent inducer of drug metabolism and alters
the plasma levels of many drugs (e.g., digoxin, quinidine,
warfarin, oral contraceptives, methadone, theophylline, antifungals,
b-blockers, calcium channel blockers). Therefore
drug-drug interactions are a major concern.
Clinical use
At therapeutic levels, rifampin is bactericidal against intracellular
and extracellular Mycobacterium tuberculosis organisms
and is used in combination with other antimycobacterials to
treat tuberculosis. Rifampin is effective against many grampositive
and gram-negative microorganisms. This antimicrobial
is the drug of choice for prophylaxis of meningococcal
meningitis. Rifampin is used prophylactically in close contacts
of patients affected by epiglottitis or meningitis caused by
Haemophilus influenzae. The drug is also used prophylactically

against leprosy and in combination with other drugs to

treat Legionella.
Adverse effects
Hepatotoxicity may occur with rifampin. For this reason, acetaminophen
should be avoided. Rifampin also discolors body
fluids, turning urine, sweat, saliva, and tears red-orange. Contact
lenses may be permanently stained. Oral contraceptive
efficacy may be severely lessened by induction of hepatic
P450 microsomal enzymes, and patients should consider alternative
contraceptive measures.

Pyrazinamide
Mechanism of action
The mechanism of action of pyrazinamide is unclear. It may
be that pyrazinamide lowers the pH in the tubercle cavity
and inhibits growth of mycobacterium.
Clinical use
This drug is often added to isoniazid and rifampin when treating
tuberculosis.

Adverse effects
Pyrazinamide is associated with gastrointestinal distress, elevated
uric acid, and hepatotoxicity. Patients should be monitored
for hyperuricemia and signs of hepatotoxicity.