AntiMycobacterium Flashcards
Pulmonary; intestinal mucosa & lymph nodes;
fatal dissemination in AIDS patients
Caused by
M. avium-intracellulare
CHALLENGING ASPECTS OF ANTIMYCOBACTERIAL THERAPY
Difficult to kill
- Difficult to grow, identify, and do susceptibility testing
- Requires very lengthy therapy
- Chronic disease
- Intracellular forms
Mycobacterial have Spontaneous resistance … thus we must use
multi-drug therapy
Goals of Therapy
- Convert cultures to negative in shortest possible time
- Prevent emergence of drug resistance
- Assure complete cure without relapse
____________ is the pathologic agent in 90% of the cases; ___________ for 10% of others
M. tuberculosis
M. avium- intracellulare (MAI)
has become a serious problem in AIDS patients
• More common in aged, dialysis patients, AIDS patients, immunocompromised,
immigrants, drug addicts, the homeless
M.avium-intracellulare
Diagnosis for Tuberculosis
- Tuberculin skin test (positive prior to symptoms)
- X-ray
- Acid-fast stain/culture
Bactericidal for actively growing bacilli, bacteriostatic for “resting cells”
Isoniazid
Isoniazid works by inhibiting synthesis of ________which are important branched hydroxy fatty
acids of mycobacterial cell walls
mycolic acids,
isoniazid is a prodrug which is
activated by ______________of the tubercle bacillus;
the activated drug’s target is the enoyl-acyl carrier protein reductase (InhA)
the catalase-peroxidase (KatG protein)
isoniazid is a prodrug which is
activated by the catalase-peroxidase (KatG protein) of the tubercle bacillus; the activated drug’s target is the ….
enoyl-acyl carrier protein reductase
(enough of this Acsinice shit)
enony-acycl for isoniazid
Resistant strains of Isoniazid often result from mutations in
KatG or InhA
Most important primary TB drug; all patients with INH-sensitive strains should
receive INH if possible
Isoniazid
For treatment, Isoniazid is always given i
n combination with other agents
Isoniazid is for tuberculosis but may also be effective against some strains of
M. bovis and M. kansasii
For prophylaxis, Isoniazid can be used alone for
(6–9 months)
• For latent TB (infected, no active disease), CDC recommends
isoniazid (9 months) or isoniazid + rifapentine (3 months)
Isoniazid has Oral or parenteral admin but should be administered with
aluminum-containing antacids interfere with absorption
Isoniazid is rapidly absorbed; readily distributes in tissue fluids, some into CSF; penetrates into caseous lesions; intracellular and extracellular levels are similar
• N-acetylation is under
genetic control (slow acetylators, t1/2 ~ 2–5 hr; rapid acetylators, t1/2 ~ 70 min)
Toxicity of Isoniazid:
Neurotoxicity, esp. peripheral neuritis — d/t thyimine defieiccy… alcoholics
• Hepatotoxicity
What causes neurotoxicity from Isoniazid
— thymine or B6 deifience
Rifampin, a macrolide for TB and it’s mechanism is:
Inhibits bacterial DNA-dependent RNA polymerase, no RNA made
Rifampin is a macrolide for TB that is bactericidal or bacteriostatic
bacteriacidal
Isoniazid Resistance: 1 in 10 to 7th or 10 to the 8th
cells have spontaneous mutation in
RNA polymerase
