Rifampin

Isoniazide

Pyrazinamide

Ethambutol 

Streptomycin, Fluoroquinolones (Moxifloxacin, gatifloxacin), Amikacin, Kanamycin, Capreomycin, Ethionamide, P-aminosalicylic acid

Toxic, lack of data, many are IV only

Cytoplasm, cell membrane, peptidoglycan, arabinogalactan, mycolic acid, superficial lipids (cord factor) 

LAM extends the length

Rifampin, Rifabutin, Rifapentine

Rifaximin (used in C diff infections; not mycobacterium infections) 

All inhibit DNA dependent RNA polymerase 

Inhibits Transcription

Highly bioavailable (except rifaximin) - highly distributed (including to CNS) 

Color secretions are orange red 

Metabolized in liver by de-acetylation -- VERY STRONG P450 CYTOCHROME INDUCER

Largely excreted by biliary tract (enterohepatic circulation) 

Very active against M tub, staphylococci, enteric GNRs

Don't use as monotherapy; resistance is usually through altered DNA dependent RNA polymerase

very strong cytochrome P450 inducer

Color secretions turn orange-red

Not common - nausea/vomiting, rash, hypersensitivity, hepatotoxicity

Less cytochrome P450 inducer

Common component of M avium-intracellurae complex

Alternative for TB

Can be used in other bacterial infections; never as a monotherapy 

Metabolized to active drug that inhibits synthesis of mycolic acids 

Specific to mycobacteria 

Very well distributed and highly absorbed - including to CNS and TB lung consolidations

Variable metabolism via acetylation by NAT2 

Genetically variable slow and rapid acetylators 

Metabolites eliminated renally 

Most important drug in TB pharmacotherapy

Active only against MT and M. kansasii

Bacteriostatic for organisms not growing; bactericidal for dividing organisms 

Resistance is due to several mechanisms (decreased fitness in mutants)

Phenytoin (not P450 related, monitor phenytoin concentrations)

Adverse effects: rash, fever, hepatotoxicity, peripheral neuropathy (treat with pyridoxime - B6), drug induced lupus, optic neuritis/seizures

MOA: inhibits arabinosyl transferase, preventing cell wall synthesis 

Inactive against non-mycobacteria 

Active against many species of mycobacteria

1st line drug in both TB and MAC infections

Resistance not common, but occurs when given as monotherapy 

Optic neuritis (decrease vision, loss of red green differentiation, test visual acuity during long term therapy)

GI effects

CNS effects possible, but rare 

Inhibits FAS1, which blocks production of fatty acid precursors of mycolic acids

Active only at a acidic pH

May be bacteriostatic or bacteriocidal 

highly absorbed, widely distributed, including to CSF

Metabolized hepatically but not by P450 

Renally eliminated, but mostly metabolites, so you would not have to renally adjust

Would be most hepatotoxic 

Pyrazinamide is only active against M. tuberculosis

Adverse effects: hepatotoxicity, arthralgias, hyperuricemia, GI effects 

Streptomycin MOA

Bactericidal or bacteriostatic

Aminoglycoside antibiotic - inhibits protein synthesis by binding to 30S ribosomal bunit, causing misreading of mRNA 

Bactericidal for most organisms; bacteriostatic for M tuberculosis 

Poorly absorbed (must be given IV or IM for systemic treatment) 

Moderate distribution (Poor to CNS, moderate to lungs, inactive in acidic environments) 

No metabolism 

Entirely renally eliminated -- can be nephrotoxic 

Streptomycin is active against TB, but not intracellularly 

Active against many GNRs and GPC

- GPC activity greatly enhanced in the presence of other agents 

Nephrotoxicity (related to elevated trough concentrations - monitor urine output, serum creatinine, streptomycin concentrations)

Ototoxicity (auditory and vestibular) - idiosyncratic, possibly related to overall exposure 

Kanamycin, Amikacin

AEs similar to streptomycin (ototoxicity, nephrotoxicity)

Other aminoglycosides are not active against TB

Inhibits D-ala-D-ala synthetase and alanine racemase, preventing peptidoglycan monomer synthesis at 2 different steps 

Second line agent 

Resistance is common

AE: psychosis and peripheral neuropathy (somewhat preventable with pyridoxine) 

Monifloxacin, gatifloxacin (not used - hypo/hyper glycemia), most active; levofloxacin also used

Also active against M. avium intracellulare 

Currently second line agents but may move up

resembles PABA, blocks folate synthesis

Relatively safe but high incidence of hypersensitivity 

Peptide antibody that functions like aminoglycoside

Ototoxic and nephrotoxic