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Classes of anti-TB drugs |
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| Agent |
Mechanism of Action |
Activity Against M. tubercolosis |
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| First-line agents |
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| Rifampicin (RIF) |
Inhibits bacterial RNA synthesis by binding to the β subunit of bacterial DNA-dependent RNA-polymerase (DDRP) Inhibition of DDRP leads to blocking of the initiation chain formation in RNA synthesis. One of the most effective antituberculosis agents available and is bactericidal for intra- and extra-cellular bacteria [4,19]. |
RIF inhibits susceptible organisms at concentrations of less than 1 μg/mL [4]. |
| Isoniazid (INH) |
Most active drug for the treatment of TB caused by susceptibe strains. Is a pro-drug activated by katG, which exerts its lethal effect through inhibition of synthesis of mycolic acids, an essential component of mycobacterial cell walls, through formation of a covalent complex with an acyl carrier protein (AcpM) and KasA, a beta-ktoacyl carrier protein synthetase [4,5] |
INH inhibits tubercle bacilli at a concentration of 0.2 μg/mL [4]. |
| Pyrazinamide (PYZ) |
Converted to the active pyrazanoic acid (encoded by pncA) by pyrazinamidase in susceptible organisms. Pyrazanoic acid lowers pH in the immediate surroundings of M. tuberculosis – organism is unable to grow. May also function as an antimetabolite of nicotinamide and interfere with the synthesis of NAD, inhibiting the synthesis of short-chain, fatty-acid precursors [4,5] |
Inhibits M. tuberculosis and other mycobacteria at concentrations of 20 μg/mL [4]. |
| Ethambutol (ETB) |
Inhibits mycobacterial arabinosyl transferases (encoded by the embCAB operon) involved in the polymerization of D-arabinofuranose to arabinoglycan, an essential cell wall component [4,5]. |
Ethambutol is generally bacteriostatic, but at high doses (25 mg/kg) can be bactericidal [20]. Inhibits susceptible strains of M. tuberculosis at concentrations of 1–5 μg/mL [4]. |
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| Aminoglycosides (injectable) Streptomycin, kanamycin, amikacin, capreomycin |
The aminoglycosides are irreversible inhibitors of protein synthesis through binding to specific 30S-subunit ribosomal proteins [4]. |
Bactericidal. In vitro and in vivo clinical data support use [21,22,23]. |
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| Fluoroquinolones Ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin, gatifloxacin, sparfloxacin |
Inhibit bacterial DNA synthesis through inhibition of bacterial topoisomerase II (DNA gyrase) and topoisomerase IV, which are responsible for the relaxation of supercoiled DNA and the separation of replicated chromosomal DNA, respectively [4]. |
Bactericidal, broad spectrum antibacterials [5]. In-vitro and in-vivo clinical data support use [24,25]. Ciprofloxacin and levofloxacin inhibit strains of M. tuberculosis at concentrations of less than 2 μg/ml. Newer agents (moxifloxacin, gatifloxacin, sparfloxacin) have lower minimum inhibitory concentrations [4,26,27]. |
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| Bacteriostatic second-line drugs |
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| Ethionamide |
Chemically related to INH, converted via oxidation to ethionamide sulfoxide, blocks the synthesis of mycolic acids [4,5]. |
Inhibits most tubercle bacilli at concentrations of 2.5 μg/mL or less [4]. |
| Cycloserine |
Structural analogue of D-alanine, inhibits incorporation of D-alanine into peptidoglycan pentapeptide through inhibition of alanine racemase [4]. |
Inhibits strains of M. tuberculosis at concentratins of 15–20 μg/mL [4]. |
| P-aminosalicylic acid |
Anti-metabolite interfering with incorporation of para-aminobenzoic acid into folic acid – folate synthesis antagonist [4,5]. |
Inhibits tubercle bacilli at concentrations of 1–5 μg/mL [4]. |
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| Other drugs |
Potentially useful agents with conflicting animal or clinical evidence or agents with unclear efficacy because of possible cross-resistance. |
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| Clofazimine |
Unknown, but may involve DNA binding [4]. Possesses direct antimycobacterial and immunosuppressive properties [4,5] |
Bacteriostatic in vitro. MIC 90 <1.0 mg in vitro [28]. Apt concentrations attainable in vivo, particularly in macrophages [29,30]. |
| Amoxicillin/clavulanic acid |
Amoxicillin (a penicillin) inhibits cell wall synthesis. Clavulinic acid is a beta-lactamase inhibitor |
β lactams in combination with beta lactamase inhibitors bactericidal in vitro [31,32,33]. |
| Clarithromycin |
Inhibition of protein synthesis via binding to 50S ribosomal RNA as aminoacyl translocation reactions and the formation of initiation complexes are blocked [4,5]. |
Although in vitro antimycobacterial properties reported, data from animal and in vivo studies conflicting [34,35,36,37]. |
| Rifabutin |
Activity is similar to that of rifampicin. Inhibits bacterial RNA synthesis by binding strongly to the β subunit of bacterial DNA-dependent RNA-polymerase [4]. |
May be useful against some isolates of MDR TB (resistant to RIF in vitro but sensitive to rifabutin) [38]. Effective in prevention and treatment of disseminated atypical mycobacterial infection in AIDS patients with CD4 counts <50 [4]. |
| Thiacetazone |
Not clearly elucidated. |
In vivo and in vitro evidence of bacteriostatic activity. Cross-resistance frequently seen between thiacetazone and both INH and ethionamide [39,40]. |
du Toit et al. Respiratory Research 2006 7:118 doi:10.1186/1465-9921-7-118 |
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