Recommended Dosage of Intravenous Imipenem/Cilastatin
The recommended dose of intravenous (IV) imipenem/cilastatin is 500 mg every 6 hours or 1000 mg every 8 hours for patients with normal renal function (creatinine clearance ≥90 mL/min). 1
Dosage Based on Renal Function
Imipenem/cilastatin requires dose adjustment based on renal function:
| Creatinine Clearance (mL/min) | Recommended Dosage |
|---|---|
| ≥90 | 500 mg every 6 hours OR 1000 mg every 8 hours |
| <90 to ≥60 | 400 mg every 6 hours OR 500 mg every 6 hours |
| <60 to ≥30 | 300 mg every 6 hours OR 500 mg every 8 hours |
| <30 to ≥15 | 200 mg every 6 hours OR 500 mg every 12 hours |
Administration Guidelines
- Administer doses ≤500 mg by intravenous infusion over 20-30 minutes
- Administer doses >500 mg by intravenous infusion over 40-60 minutes
- For patients who develop nausea during infusion, the rate may be slowed 1
Special Populations
Pediatric Dosing
- Children ≥3 months: 15-25 mg/kg every 6 hours
- Children 4 weeks to 3 months: 25 mg/kg every 6 hours
- Children 1-4 weeks: 25 mg/kg every 8 hours
- Children <1 week: 25 mg/kg every 12 hours 1
Specific Infection Types
For carbapenem-resistant Enterobacterales (CRE):
- Bloodstream infections: 1.25 g IV every 6 hours
- Complicated urinary tract infections: 1.25 g IV every 6 hours
- Complicated intra-abdominal infections: 1.25 g IV every 6 hours 2
Pharmacological Considerations
Imipenem is always administered with cilastatin in a 1:1 ratio. Cilastatin inhibits the renal metabolism of imipenem by dehydropeptidase I, increasing urinary recovery of active imipenem to approximately 70% of the dose 3. Without cilastatin, urinary recovery of unchanged imipenem would only be 5.5-42.5% of the dose 3.
Treatment Duration
Treatment duration should be individualized according to:
- Infection site
- Source control success
- Underlying comorbidities
- Initial response to therapy 2
Typical durations:
- Bloodstream infections: 7-14 days
- Complicated urinary tract infections: 5-7 days
- Complicated intra-abdominal infections: 5-7 days 2
Important Considerations and Potential Pitfalls
- Maximum daily dose: Do not exceed 4 g/day total 1
- Hemodialysis patients: Both imipenem and cilastatin are efficiently removed during hemodialysis; a supplementary dose after dialysis is recommended 4
- Monitoring: Perform routine toxicity monitoring (complete blood count, renal function, liver function tests) throughout treatment 2
- Common adverse effects: Nausea, vomiting, diarrhea, rash, thrombophlebitis (3%), eosinophilia (4%) 2
- Serious adverse effects: Seizures (especially with CNS infections or renal impairment), anaphylaxis, C. difficile-associated diarrhea 2
Drug Interactions
- Ganciclovir: Increased risk of convulsions
- Valproate: Reduced serum concentrations of valproate; avoid concomitant use 2
Remember that imipenem/cilastatin is a potent broad-spectrum antibiotic that should be used judiciously to prevent the development of antimicrobial resistance.