antibiotics used to treat TB

see also:

• tuberculosis (TB)
• antibiotics

• a hydrazide of isonicotinic acid, discovered in 1945 after nicotinamide shown to have anti-TB action
• remarkably selective for TB, and is the primary drug used in Rx of TB
• bacteriostatic for resting bacteria but bactericidal for rapidly dividing bacteria
• adverse effects:
  • rash (2%); fever (1.2%); jaundice (0.6%); peripheral neuritis (0.2% - higher if pyridoxine not given); HS;
  • convulsions in pts with PH seizures
  • hepatotoxicity - esp. if elderly, slow acetylators, alcoholic hepatitis
• drug interactions - phenytoin toxicity;

• a semi-synthetic derivative of a member of the structurally similar, complex macrocyclic antibiotics produced by Streptomyces mediterranei
• inhibits DNA-dependent RNA polymerase leading to suppression of initiation of chain formation (but not elongation) in RNA synthesis.
• mammalian mitochondrial RNA polymerase is also inhibited but only at higher concentrations than is needed for antimicrobial effect
• inhibits the activity of:
  • most gram-positive bacteria including Staph.aureus,
  • many gram -ves ( such as E.coli, Pseudomonas, Proteus & Klebsiella)
  • Neisseria meningitides but resistance develops rapidly!
  • Haemophilus influenzae
  • Legionella
  • most Mycobacterium but resistance develops rapidly!
• adverse effects:
  • generally well tolerated
  • orange-red discoloration of tears, saliva, urine, faeces ⇒ stains contact lenses
  • potent inducer of hepatic enzymes ⇒ drug interactions (eg. reduced levels of warfarin, digoxin, sulphonylureas, methadone, etc)
  • effect starts 5-8 days after onset of Rx and ceases 5-7 days after Rx ceased
  • impairs effectiveness of OCP via enhanced catabolism of steroids
  • at usual anti-TB doses:
    • 0.8% rash; 0.5% fever; 1.5% nausea/vomiting
    • 85% light chain Ig proteinuria
    • fatal hepatitis 32 per million pts treated - higher risk if liver impairment, alcoholism or old age
  • at doses 1200mg/day or more &/or on less than twice weekly dosing:
    • 20% flu-like syndrome of fever, chills, myalgias and may include:
    • eosinophilia
    • interstitial nephritis
    • acute tubular necrosis
    • thrombocytopenia
    • haemolytic anaemia
    • shock
  • C/I to rifampicin:
    • pregnancy / breast feeding
    • jaundice
    • Hx of renal or liver impairment
    • HS
  • precautions:
    • contact lenses
    • other medications such as OCP
    • must be taken 1 hr before meals or > 2hrs after meals
  • clinical uses:
    • meningococcal prophylaxis:
      • adults: 600mg bd for 2 days or 600mg once a day for 4 days
      • children: 10-20mg/kg to max. 600mg per dose
    • TB:
      • adults: 600mg once daily
      • children: 10mg/kg once daily to max. 600mg

• adverse effects:
  • optic neuritis (red-green color blindness):
    • <1% pts on < 15mg/kg/d
    • 5% pts on 15-25mg/kg/d
    • 15% pts on 50mg/kg/d

• the 1st clinically effective drug for TB, but now the least used 1st line agent & mainly only used in disseminated TB or meningitis
• see under aminoglycosides
• adverse effects:
  • 4% - auditory/vestibular effects
  • 2% - rash

• in 2014, it was announced a new drug regime called PaMZ appeared to cure multi-resistant TB in only 4 months Rx compared with the usual 2 yr Rx with 71% cleared after 8wks Rx compared with 38% with standard Rx
• consists of:
  • PA-824 (Pa)
  • moxifloxacin (M)
  • pyrazinamide (Z)
• phase 3 study is pending

• bedaquiline
  • side effects can include liver toxicity and heart failure