Antimycobacterial Agents
Mycobacterium Tuberculosis
- In patients < 35, with suspected exposure to TB with positive PPD and no clinical symptoms
Ø Isoniazid – 6-9 months
- In patients with a positive X-Ray, &/or positive smear of TB give 1st line agents
Ø Isoniazid – 6 months – inhibits cell wall synthesis
Ø Rifampin – 6 months – inhibits RNA polymerase
Ø Pyrazinamide – at least 2 months
Ø Ethambutol – for resistant strains
- Treatment of resistant strains of TB – use 2nd line agents in addition to at least 2 first line agents to which the organism is susceptible
Ø Ethionamide, Ciprofloxacin, Ofloxacin, Capreomycin, PAS
- IF PREGNANT
Ø Use: INH, RIF, EMB, pyridoxine
Ø Don’t use – Pyrazinamide, Ags, Quinolones, Ethionamide
- If contracts TB meningitis
Ø use Pyrazinamide (75-100% CNS penetration), Ethionamide (100%), INH (20-100%)
Mycobacterium Avium-intracellulare complete (MAC)
- occurs predominantly in AIDS patients
- No known effective therapy
- Try to use:
Ø Amikacin, Ciprofloxacin, Clarithromycin (prophylaxis), Rifabutin, Ethambutol
M. fortuitum, M. chelonae
- rapid growers
- usually cause of chronic wound infections
- use: Amikacin, Cephalosporins, Imipenem
First Line Anti-TB drugs – INH, Rifampin, Rifabutin, Ethambutol, Streptomycin, Pyrazinamide
Isoniazid
- inhibits cell wall synthesis
- most active anti-TB agent; penetrates the CSF well
- Bactericidal for TB
- Side effect – hepatitis
- There are slow and rapid acetylators
- Drug interactions
Ø Phenytoin – inhibits the parahydroxylation – monitor for toxicity
- Add Vit B-6 (Pyridoxine) to regimen
Rifampin, Rifabutin
- inhibit bacterial RNA polymerase
- bactericidal for intracellular and extracellular TB
- Rifabutin effective against MAC – 30% of strains resistant to rifampin are susceptible to rifabutin
- ORANGE COLOR TO SECRETIONS
- Drug interactions
- decreases t1/2 of prednisone, digitoxin, ketoconazole, propranolol
- decreases the effectiveness of oral contraceptives
- Contraindications: HIV patients
Ethambutol
- Inhibits Mycobacterial arabinosyl transferases encoded by cmb-CAB operon, therefore esssential arabinoglycan can’t be produced for the cell wall
- Bacteriostatic
- Poor CSF penetration
- Side effect: visual disturbances
- Inhibits cell wall synthesis
Streptomycin (aminoglycoside)
- bactericidal for TB
- has to be given IM
- ototoxicity and nephrotoxicity
- among other aminoglycosides, Amikacin more effective against MAC and rapid growers
Pyrazinamide
- Unknown mechanism, but does its killing inside of macrophages
- Bactericidal for TB at acidic pH (within MACS)
- Good CSF penetration
2nd Line Anti-TB Drugs – Ethionamide, PAS, Quinolones
Ethionamide
- blocks synthesis of mycolic acids
- not commonly used
- good CSF penetration
Para-Aminosalicylic Acid
- Bacteriostatic
- Inhibits folic acid synthesis in mycobacteria
- not often used
Quinolones – Ciprofloxacin, Ofloxacin
- some activity against TB and MAC and fortuitum
- concentrate in lung
Other Antimycobacterial Agents – Dapsone, Clofazimine
Dapsone
- related to sulfas
- used in combo with Rifampin & Clofazimine for treatment of M. leprae
- 2 years of treatment
Clofazimine
- bactericidal against M. leprae
- also acts in an anti-inflammatory manner to prevent the erythema nodosum leprosum
- also has a little activity against M. ulcerans and MAC
- RED discoloration of the skin may develop.
Tags: aminoglycoside, Capreomycin, Ciprofloxacin, Ethambutol, Ethionamide, Mycobacterium Tuberculosis, Ofloxacin, Pyrazinamide, Quinolones, Rifampin, streptomycin
