18 Metronidazole, Fidaxomycine, Rifaximin, Urinary antiseptics, Phosphomycine

Question 1

What are the imidazole drugs?

Answer 1

• Metronidazole
• Tinidazole

Question 2

What is the mechanism of action of metronidazole?

Answer 2

• Produce toxic intermediary metabolites (reduction of N₂O group) in anaerobic conditions ==> DNA damage
• Bactericidal

Question 3

What is the spectrum and clinical use of metronidazole?

Answer 3

Spectrum:

• Anaerobe gram (-) bacteria (B. fragilis, fusobacteria)
• C. difficile
• Anaerobe gram (+) cocci and rods (the effect is weaker, resistance)
• H. pylori, Campylobacter
• Protozoons (trichomonas, G. lamblia, amoeba)

Clinical use:

• Anaerobic or mixed intraabdominal infections
• Vaginitis, stomatitis (trichomonas)
• Cl. Difficile:
  
  • Induced colitis (IV or oral)
• Brain abscesses
• Extraluminal amebiasis

Question 4

What are the pharmacokinetics of metronidazole?

Answer 4

• Good absorption
• Wide distribution (CNS and abscesses)
• Metabolized in the liver
• Elimination through the bile
• Administration:
  
  • Oral, IV, topical
  • 3x/day
• Tinidazole: slow elimination, 1x/day

Question 5

What are the adverse effects of metronidazole?

Answer 5

• GI disturbances:
  
  • Nausea, metallic taste, diarrhea, stomatitis
• Neurological disturbances:
  
  • Headache, dizziness, ataxia, paresthesia, peripheral neuropathy
• Alcohol-intolerance
  
  • “Disulfiram-like effect”: hangover is felt immediately after consumption of alcohol

Question 6

What are the macrocyclics?

Answer 6

Fidaxomycine

Mechanism of action:

• It is a protein synthesis inhibitor:
  
  • Inhibition of RNA polymerase (binding site differs of that of rifamicins) ==> ø transcription
• Bactericidal
• Long PAE

Pharmacokinetics:

• Minimal absorption, primarily remains in GIT (ideal to treat clostridium difficile)
• Administration:
  
  • Oral
  • 2x/day

Spectrum:

• Very narrow spectrum:
  
  • Gram (+) aerobes and anaerobes
• Mainly used against clostridium difficile

Adverse effects:

• Nausea, vomiting
• Abdominal pain
• Hypersensitivity reactions
• Possible anemia and neutropenia

Question 7

What is rifamixin?

Answer 7

Spectrum:

• Gram (+)
  
  • Staph, strep, enterococcus
• Gram (-)
  
  • Moderate action against intestinal bacteria, but doesn’t absorb from GI

Pharmacokinetics:

• Oral administration

Clinical use:

• Hepatic encephalopathy
• Prophylaxis before colorectal surgery
• Acute (non-inflammatory) enteritis
• Colitis

Question 8

What are the urinary antiseptics?

Answer 8

• Nitrofurans:
  
  • Mechanism of action: affects the ribosomal proteins?
  • Spectrum: E. coli, E. fecialis, …
  • Pharmacokinetics: High concentration only in the urine
  • Indication: non-complicated lower UTI (in pregnancy, in children, in case of resistance)
  • Adverse effects:
    
    • GI disturbances
    • Acute hypersensitivity, pulmonary reaction, chronic pulmonary reaction
    • Neuropathies

Question 9

What is phosphomycin?

Answer 9

Mechanism of action:

• Cell wall synthesis inhibitor:
  
  • Inhibits the 1^st step in the formation of UDP-N-acetylmuramic acid

Spectrum:

• Gram (+) and (-) bacteria

Pharmacokinetics:

• Good absorption
• High concentration in urine

Adverse effects:

• Moderate GI disturbances

Phosphomycin-trometamo prodrug:

• Single 3g dose for lower UTI or as a prophylactic purpose (2x)
• Can be used in pregnancy
• Not used in children < 12-years-old