imipenem-cilastatin
Brand: Primaxin
Prototype Drug
Drug Class: carbapenem antibiotic
Drug Family: antibiotic
Subclass: carbapenem with renal dehydropeptidase inhibitor
Organ Systems: infectious-disease
Mechanism of Action
Imipenem binds PBPs to inhibit cell wall synthesis; cilastatin is a specific inhibitor of renal dehydropeptidase-I that prevents hydrolytic inactivation of imipenem in the kidney, maintaining therapeutic urinary concentrations and reducing nephrotoxicity.
penicillin-binding proteins (PBPs)renal dehydropeptidase-I
Indications
- complicated urinary tract infections
- intra-abdominal infections
- lower respiratory tract infections
- skin/soft tissue infections
- bone and joint infections
- septicemia
- endocarditis (non-MRSA)
- febrile neutropenia (empiric)
Contraindications
- beta-lactam hypersensitivity
- seizure disorders (relative)
- CNS infections (due to seizure risk)
Adverse Effects
Common
- nausea
- vomiting
- diarrhea
- injection site reactions
Serious
- seizures (especially with renal impairment or high doses)
- C. difficile colitis
- anaphylaxis
- encephalopathy
Pharmacokinetics (ADME)
| Absorption | IV only |
| Distribution | widely distributed; penetrates CSF (inflamed meninges only marginally — NOT drug of choice for meningitis) |
| Metabolism | imipenem metabolized by renal dehydropeptidase-I (inhibited by cilastatin); cilastatin not metabolized |
| Excretion | renal (70% imipenem, 70% cilastatin unchanged) |
| Half-life | 1 hour |
| Onset | immediate (IV) |
| Peak | end of infusion |
| Duration | 6–8 hours |
| Protein Binding | imipenem 20%; cilastatin 40% |
| Vd | moderate |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| valproate | imipenem reduces valproate serum levels, potentially causing loss of seizure control; avoid combination | major |
| ganciclovir | additive risk of seizures | major |
| cyclosporine | possible additive nephrotoxicity and CNS toxicity | moderate |
Nursing Considerations
- Monitor patients with a history of seizure disorders closely; reduce dose or use an alternative carbapenem (meropenem or ertapenem have lower seizure risk) when seizure risk is high.
- Critical renal dose adjustment required: reduce dose AND extend interval as CrCl falls; failure to adjust dramatically increases seizure risk.
- Do NOT use imipenem-cilastatin for bacterial meningitis; poor CNS penetration and seizure risk make meropenem the preferred carbapenem for CNS infections.
- Monitor for C. difficile infection with new or worsening diarrhea during and after therapy.
Clinical Pearls
- Imipenem-cilastatin has the broadest spectrum of any beta-lactam, covering gram-positives, gram-negatives, and anaerobes, including Pseudomonas aeruginosa and most ESBL producers.
- The cilastatin component serves a purely pharmacokinetic function (dehydropeptidase inhibition) and has no antibacterial activity; imipenem without cilastatin would be rapidly inactivated in the kidney.
Safety Profile
Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.