Pharmacology of Vancomycin

Cell Wall Synthesis Inhibitors

• Vancomycin:

  • Bactericidal, inhibits cell wall synthesis
  • Effective against Gram-positive organisms
  • Pharmacokinetics:
    • Administered by IV infusion, but given orally for antibiotic-induced pseudomembranous colitis
    • Excreted renally, dosage adjusted in renal dysfunction
  • Therapeutic uses:
    • Oxacillin-resistant Staph aureus (ORSA)
    • Serious allergy to penicillins
    • Pseudomembraneous colitis following antibiotic use
  • Adverse effects:
    • Fever, rigors, and phlebitis
    • Shock with rapid infusion (Red Man Syndrome) due to histamine release
    • Hearing affection or loss
    • Renal dysfunction

• Bacitracin:

  • Effective against Gram-positive organisms
  • Restricted to topical application due to potential nephrotoxicity

Protein Synthesis Inhibitors

• Tetracyclins (Tetracyclin, Doxycyclin, Minocyclin, Demeclocyclin):

  • Mechanism of action: binding to 30S ribosomal subunit, inhibiting protein synthesis
  • Therapeutic uses:
    • Chlamydial infections
    • Cholera
    • Amoebiasis
    • Acne vulgaris
    • Mycoplasma pneumonia
    • Meningococcal carriers
    • Brucellosis
  • Adverse effects and contraindications:
    • Epigastric pain due to gastric irritation
    • Teeth discoloration and bone hypoplasia (contraindicated in pregnancy, lactation, and children < 8 years)
    • Hepatotoxicity
    • Phototoxicity

• Macrolides (Erythromycin, Clarithromycin, Azithromycin, Roxithromycin):

  • Mechanism of action: inhibition of protein synthesis by binding to 50S bacterial ribosomal subunits
  • Spectrum and uses of erythromycin:
    • Drug of choice in patients with spirochetes or Gram-positive coccal infections with allergy to β-lactam antibiotics
    • Drug of choice in urogenital chlamydial infection in pregnancy and mycoplasma pneumonia in children
  • Adverse effects of erythromycin:
    • Epigastric pain and intestinal colic
    • Cholestatic jaundice (contraindicated in liver disease)
    • Ototoxicity and transient deafness
    • Thrombophlebitis if injected IV

• Clindamycin & Chloramphenicol:

  • Mechanism of action: binding to 50S ribosomal subunit, inhibiting protein synthesis
  • Clindamycin:
    • Used specifically against anaerobic infections
    • Effective against Gram-positive organisms (Staph and Strept.)
    • Used in bone infections due to good penetration into bones
  • Adverse effects of clindamycin:
    • Pseudomembraneous colitis
    • Skin rash
    • Diarrhea
    • Liver dysfunction
  • Chloramphenicol:
    • Therapeutic uses:
      • Typhoid fever (replaced by fluoroquinolones)
      • Bacterial meningitis (H.influenza) + penicillin
      • Topical use in eye infections (e.g., conjunctivitis)
      • Anaerobic infections (e.g., anaerobic brain abscess)
    • Adverse effects of chloramphenicol:
      • GIT upset and superinfection
      • Bone marrow depression (dose-independent or idiosyncrasy)
      • Grey baby syndrome in neonates
      • Optic neuritis
      • Inhibition of hepatic microsomal enzymes (drug interaction)

• Clofazimine:

  • Mechanism of action: unknown, possibly DNA binding
  • Anti-inflammatory effect
  • Absorption: variable from gut, given orally once daily
  • Excretion: mainly in feces, storage in reticuloendothelial tissues and skin
  • Half-life: 2 months, delayed onset of action (6 weeks)
  • Clinical uses:
    • Multidrug resistance TB
    • Lepromatous leprosy
    • Tuberculoid leprosy in patients intolerant to sulfones or with dapsone-resistant bacilli
    • Chronic skin ulcers caused by M.ulcerans
  • Adverse effects:
    • Skin discoloration (red-brown to black)
    • Gastrointestinal intolerance
    • Red color urine
    • Eosinophilic enteritis

Treatment of TB in Pregnant Women

• INH (with pyridoxine), Rifampicin, Ethambutol
• Pyrazinamide only if:
  • Resistant to other drugs is documented
  • Streptomycin is contraindicated
• Breastfeeding is not a contraindication, but caution should be observed

Antiprotozoan Drugs

• Protozoa are eukaryotic cells
• Many drugs are experimental, and their mode of action is unknown

Amoebiasis

• Infection with Entameba histolytica produced by ingestion of cysts
• In the intestine, cysts develop into trophozoites (active invasive form) which adhere to colonic epithelial cells
• Trophozoites lyse host cells and invade the submucosa, resulting in:
  • Bowel lumen amoebiasis: asymptomatic, but cysts pass in the stool, transmitting infection to others
  • Treatment is directed at eradicating cysts with luminal amebicidal drugs:
    • Diloxanide
    • Iodoquinol
    • Paromomycin
    • Tetracyclin