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Carbapenem Antibiotics
Introduction
Carbapenems are a class of broad-spectrum β-lactam antibiotics that are used primarily to treat infections caused by multidrug-resistant organisms. They work by inhibiting the synthesis of bacterial cell walls, leading to bacterial cell death.
Examples
- Imipenem/cilastatin
- Meropenem
- Ertapenem
- Doripenem
Mechanism of Action
Carbapenems inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), disrupting peptidoglycan cross-linking. This causes bacterial cell lysis and death. Carbapenems are bactericidal in action.
Mechanism of Resistance
- β-lactamase production (carbapenemases) that degrade the β-lactam ring.
- Altered penicillin-binding proteins (PBPs) with reduced affinity for carbapenems.
- Efflux pumps that pump the drug out of bacterial cells.
- Decreased permeability of the bacterial outer membrane, limiting carbapenem entry.
Therapeutic Uses
- Complicated intra-abdominal infections
- Complicated skin and soft tissue infections
- Pneumonia (including hospital-acquired pneumonia)
- Meningitis caused by resistant organisms
- Urinary tract infections
- Sepsis
Adverse Effects
- Gastrointestinal: nausea, vomiting, diarrhea
- CNS: seizures (especially with imipenem)
- Hypersensitivity: rash, anaphylaxis
- Hematologic: thrombocytopenia, neutropenia
- Renal toxicity: especially in renal impairment
- Clostridium difficile-associated diarrhea
Contraindications
- Allergy to β-lactam antibiotics
- History of seizures
- Severe renal impairment (requires dosage adjustment)
- Pregnancy (category C; use only when necessary)
