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Microbiology ` microbiology—aNtimicrobials Microbiology ` microbiology—aNtimicrobials SEcTioN ii 197

Isoniazid
mecHaNism  synthesis of mycolic acids. Bacterial catalase-
peroxidase (encoded by KatG) needed to
convert INH to active metabolite.
cliNical Use Mycobacterium tuberculosis. The only agent Different INH half-lives in fast vs slow
used as solo prophylaxis against TB. Also used acetylators.
as monotherapy for latent TB.
aDVerse eFFects Hepatotoxicity, cytochrome P-450 inhibition, INH Injures Neurons and Hepatocytes.
drug-induced SLE, anion gap metabolic
acidosis, vitamin B 6 deficiency (peripheral
neuropathy, sideroblastic anemia), seizures
(in high doses, refractory to benzodiazepines).
Administer with pyridoxine (B 6 ).
mecHaNism oF resistaNce Mutations leading to underexpression of KatG.

Pyrazinamide

mecHaNism Mechanism uncertain. Pyrazinamide is a prodrug that is converted to the active compound
pyrazinoic acid. Works best at acidic pH (eg, in host phagolysosomes).

cliNical Use Mycobacterium tuberculosis.
aDVerse eFFects Hyperuricemia, hepatotoxicity.

Ethambutol

mecHaNism  carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase.
cliNical Use Mycobacterium tuberculosis.
aDVerse eFFects Optic neuropathy (red-green color blindness, usually reversible). Pronounce “eyethambutol.”

Streptomycin

mecHaNism Interferes with 30S component of ribosome.
cliNical Use Mycobacterium tuberculosis (2nd line).
aDVerse eFFects Tinnitus, vertigo, ataxia, nephrotoxicity.

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