Mycobacterial Treatment Flashcards
Characteristics of Mycobacteria Shape Stain Replication location Growth pace May form? Cell walls are rich in?
Rod shaped Acid fast stain...they don't gram stain Replicate within macrophages Generally slow growing May form filaments Lipid-rich cell walls
Most infected individuals have what kind of infections?
Latent infections
Transmission is primarily through
Respiratory droplets
When may TB become disseminated?
In immunocompromised individuals
Features of latent TB infections activation state chest xray sputum and cultures symptom presentation infectious state case or not
Inactive and non-replicating Chest xray normal Sputum and cultures are negative Asymptomatic Not infectious Not a case of TB
Features of TB disease activation state chest xray sputum and cultures symptom presentation infectious state case or not
Active and replicating Abnormal chest xray Sputum and cultures MAY be positive Symptomatic Often infectious before treatment A case of TB
Obstacles to TB Treatment
organism grows slowly
organism remains viable but dormant
rapid development of resistance
toxicity with treatment–encourages non-compliance
Solutions to obstacles
Regimens contain multiple drugs
Drugs taken regularly
Drug therapy continues for long time
Rifamycin MOA
Inhibits RNA synthesis
Streptomycin MOA
useful for
Inhibition of protein synthesis at 30S
Used for combination treatment of RESISTANT TB
Isoniazid and ethionamide MOA
inhibit mycolic acid synthesis
Ethambutol MOA
Inhibits cell wall synthesis
Pyrazinamide MOA
Inhibits membrane synthesis
M. avium complex (MAC) causes pulmonary disease and disseminated disease in which populations
Pulmonary disease in immunocompetent patients
Disseminated disease in immunocompromised patients, mainly AIDS patient population
MAC primarily acquired through which route?
Ingestion of contaminated food and water
Preferred Regimen (4 drugs)
Isoniazid
Rifamycin
Pyrazinamide
Ethambutol
Continuation Regimen (2 drugs)
Isoniazid
Rifamycin
Treatment Regimen for Latent TB (3 drugs)
Which one is drug of choice for latent TB?
Isoniazid* drug of choice
Rifapentine
Rifampin
INH is bactericidal for?
Penetrates which cell type?
One reason it can cause peripheral neuropathy
Bactericidal for actively growing bacilli
Penetrates macrophages
Structurally similar to pyridoxine
INH MOA
Delivered as a…?
What activates INH
Inhibits synthesis of mycolic acid (essential component of cell wall)
Delivered as a prodrug and is activated by mycobacterial catalase-peroxidase enzyme (Kat G)
INH microbial activity
considered one of the safest and msot effective antimycobacterial agents available
Two reason for resistance against INH
- mutation in Kat G gene (no longer activated)
2. Overexpression of the InH A protein (involved in mycolic acid synthesis)
What group of people are more prone to develop toxicity from INH?
Slow acetylators (inactivators)
The risk of INH induced hepatitis increases with (blank) and is greater in individuals with (blank)
Increases with age and alcoholics
Peripheral neuropathy most commonly seen in (5)
- Slow metabolizers
- Malnourished
- Alcoholics
- Diabetic
- AIDS
Rifampin MOA
Inhibits RNA synthesis by binding to bacterial DNA-dependent RNA polymerase
Penetrates most tissues as well as phagocytic cells
Most common side effect with Rifampin use in those with liver disease?
Hepatitis
HIV patients and rifampin use
Rifabutin should be substituted for rifampin
Pyrazinamide is used almost exclusively in…
combination therapy
Pyrazinamide activated by
bacterial pyrazinamidase enzyme
Pyrazinamide is highly effective against
intracellular mycobacteria
Most common side effect associated with Pyrazinamide
Hyperuricemia/gout issues
Ethambutol used almost exclusively for…
But also used for
Part of the 4 drug combinations used to treat active TB
Also used to treat MAC bacteria
Ethambutol MOA
Inhibits arabinosyl transferases which are involved in mycobacterial cell wall synthesis
Ethambutol resistance
Point mutations in genes coding for arabinosyl transferases
Ethambutol adverse reactions (2)
- Retrobulbar neuritis/color blindness
2. Hyperuricemia (less frequent that pyrazinamide)
Streptomycin current use
Treatment of TB caused by resistant strains
Streptomycin MOA
Works well against…
Interferes with bacterial protein synthesis
Works on extracellular organisms
Rifabutin use (2)
- Greater activity against MAC organisms that rifampin
2. Substituted for rifampin in the treatment of HIV patients who also have TB
MAC treatment (3…maybe 4)
- Macrolide
- Rifampin (or other rifamycin)
- Ethambutol
- May use streptomycin
Multidrug regimen of leprosy (3)
Dapsone
Clofazimine
Rifampin
