EXAM #4: TREATMENT OF MYCOBACTERIA Flashcards
What kind of infection is caused by MAC in the immunocompetent?
Pulmonary
What kind of infection is caused by MAC in the immunocompromised?
Disseminated
What are the important characteristics of Mycobacterium?
1) Rod-shaped
2) Lipid rich cell wall with MYCOLIC ACID
3) Poor gram staining
4) ACID FAST
5) Slow growing*
Makes these bacteria challenging drug targets
What cells can Mycobacterium replicate in?
Macrophages
How is Mycobacterium Tuberculosis transmitted?
Respiratory droplets
What is Latent TB?
Infection with INACTIVE MTB
- Asymptomatic
- PPD positive
- Negative CXR
What is Active TB?
Active infection with MTB
- Symptomatic
- Positive CXR
- Infectious
What are the obstacles to MTB treatment?
1) Slow growing/ dormant
2) Develop resistance
3) Toxicity of drugs
What are the solutions to the obstacles of MTB treatment?
1) Multiple drug regimines
2) Drugs taken regularly
3) Drug therapy for sufficient time
What is direct observed therapy?
Therapy that is directly observed by a public health worker to ensure compliance
List the drugs that are approved for the treatment of TB.
Rifamycin Streptomycin Isoniazid Ethionamide Pyrazinamide
What is the most important drug for treating both latent and active TB? How much resistance is seen to this drug?
Isoniazid
*10% of TB strains are resistant to TB
How is MAC acquired?
- Ingestion of contaminated food and water
- Respiratory droplets (less frequent)
How is the preferred treatment for active TB?
1) RIPE therapy for 8 weeks
2) RI only for 18 weeks
Rifampin
Isoniazid
Pyrazinamide
Ethambutol?
How is latent TB treated?
Isoniazid for 9 months
What is the MOA of Isoniazid (INH)?
Inhibits the synthesis of mycolic acid (cell wall)
*Note that is is given as a Prodrug
What enzyme from MTB converts INH into the active form?
Mycobacterial catalase peroxidase enzyme (Kat G)
What are the resistance mechanisms associated with INH?
1) Kat G mutations–can’t activate the drug
2) Increased mycolic acid synthesis
How is INH metabolized?
Acetylation
What is the implication of “slow acetylation” in INH therapy?
More toxicity seen in slow acetylators
What are the major toxicities associated with INH?
1) Hepatitis
2) Peripheral neuropathy
Note that the hepatitis seen with INH is WORSE in alcoholics
What increases the risk of peripheral neuropathy with INH aside from slow acetylation?
1) Malnourishment
2) Alcoholism
3) DM
4) AIDS
What is the MOA of Rifampin?
Inhibition of RNA synthesis
- Binds bacterial DNA-dependent RNA polymerase
What causes resistance to Rifampin?
Point mutations in bacterial DNA-dependent RNA polymerase
