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antibiotics_tb

antibiotics used to treat TB

Isoniazid

  • 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;

Rifampicin:

  • 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

Ethambutol

  • 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

Streptomycin

  • 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

Others

Pyrazinamide

Aminosalicylic acid

PaMZ regime for multi-resistant TB

  • 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
antibiotics_tb.txt · Last modified: 2020/04/13 11:10 by gary1