Antimycobacterial Drugs

Question 1

Antimycobacterial Drugs

Answer 1

Tuberculosis caused by Mycobacterium tuberculosis

Difficult to treat for several reasons
Mycobacteria replicate more slowly than typical bacteria like E. coli or staph; pharmacotherapy is more difficult because rapidly dividing cells are more metabolically active and therefore susceptible to antibiotic chemotherapy

Can exist in a dormant state (makes them resistant to nearly all antibiotics)
In the host they live inside human cells (antimicrobials that have poor intracellular penetration are ineffective)

Have cell walls that are structurally different from typical G+ and G- bacteria
Outermost layer of mycobacteria consists of phospholipids and mycolic acids that make a waxy layer (resists penetration from antibiotics)
Arabinogalactan and peptidoglycan are polysaccharide components of the cell wall (peptidoglycan is not accessible to beta lactams- are poorly active)

Pharmacotherapy is complex
Combo of drugs always given for active disease to minimizes development of resistance and shorten duration of therapy

Combos frequently have PK drug interactions with each other and other meds the patient is on (in part because immunocompromised are particularly vulnerable to mycobacterial disease and tend to be on drugs with many interactions)

Mycobacteria grow slowly so standard susceptibility takes weeks instead of days (empiric regimens often given for extended durations)

Standard of care for active infection is a four drug regimen (compliance and drug interaction monitoring is important)

Mycobacterium avium-intracellulare complex (MAC)

Multi drug resistant TB requires a specialist

These antimycobacterial drugs previously discussed
FQ (Moxifloxacin particularly active)
Macrolides
AMG

Each first line drug has a characteristic toxicity