Carbapenem & Monobactum

CARBAPENEM & MONOBACTUM

• Are beta-lactam antibiotics.
• Beta-lactam antibiotics – Drugs containing ß–lactam ring in their structure.
• Drugs:
  • Penicillins
  • Cephalosporins (above both discussed separately)
  • Monobactams e.g. aztreonam
  • Carbapenems e.g. imipenem

General features:

• All ß-lactam antibiotics are bactericidal drugs.
• MOA: 
  • Bind to specific receptors (penicillin-binding proteins; PBPs) on bacterial cell membrane.
  • Inhibits transpeptidase enzyme
  • Responsible for peptidoglycan chain cross-linking.
  • Bacteria formed in drug presence are without cell wall –> Dies due to water imbibition. (cell wall provides turgidity).

I) Monobactams:

• Only beta-lactam antibiotic for patients with severe penicillin or cephalosporins allergy
• Since not cross allergenic.
• Drugs: Aztreonam.
  • Active against β-lactamase producing gram negative rods including Pseudomonas.
  • No activity against gram-positive organisms or anaerobes.
  • Administered i.v.
  • Prolonged half-life in renal failure.

II) Carbapenems:

• Are β-lactamase resistant.
• DOC for Enterobacter, Klebsiella & acinetobacter species.
• Wide spectrum of activity – Including gram-positive cocci, gram-negative rods & anaerobes.
• Only β-lactams, reliably efficacious against ESBL (extended spectrum β-lactamase) producing organisms.

Drugs: Imipenem, doripenem, meropenem & ertapenem.

Uses:

• For Pseudomonas treatment:
  • Meropenem – Most active & Ertapenem – least.
  • Should be combined with aminoglycosides.

Individual drug description:

• Imipenem:
  • Rapidly inactivated by renal dehydropeptidase I enzyme.
  • Always combined with cilastatin.
  • Increases imipenem half-life.
  • Inhibits nephrotoxic metabolite formation.
• (Note on cilastatin: Inhibitor of renal dehydropeptidase I enzyme).
• Adverse effects:
  • Imipenem-cilastatin combination include seizures & gastrointestinal distress (Main).
• Meropenem, doripenem & ertapenem:
  • Not metabolized by renal dehydropeptidase.
  • Hence, less likely seizures.
• Ertapenem:
  • Very long acting.
  • Inactive against Pseudomonas.
• Loracarbef:
  • Chemically similar to cefaclor.
  • Oral drug.
  • Overdose can cause seizures.

Don’t Forget to Solve all the previous Year Question asked on CARBAPENEM & MONOBACTUM