Imipenem Dosing in Renal Impairment
For patients with mild to moderate infections and impaired renal function, imipenem/cilastatin requires dose reduction based on creatinine clearance, with 500 mg every 12 hours recommended for patients with CrCl 20-40 mL/min and 250-500 mg every 12 hours for CrCl 41-70 mL/min. 1
Standard Dosing Framework
Normal Renal Function (CrCl ≥90 mL/min)
For patients with preserved kidney function, the standard dosing regimens are 1:
- 500 mg every 6 hours for mild to moderate infections
- 1,000 mg every 8 hours for moderate to severe infections
- 1,000 mg every 6 hours for severe or life-threatening infections
The 2017 WSES guidelines specifically recommend 1 g every 8 hours for critically ill patients with healthcare-associated intra-abdominal infections 2.
Renal Impairment Dosing
Critical principle: Dose reduction is mandatory when CrCl falls below 90 mL/min 1. The FDA label provides clear guidance that patients with creatinine clearances less than 15 mL/min should not receive imipenem/cilastatin unless hemodialysis is instituted within 48 hours 1.
For mild to moderate infections in patients with renal impairment:
- CrCl 41-70 mL/min: Reduce to 250-500 mg every 6-8 hours 1
- CrCl 21-40 mL/min: Reduce to 250-500 mg every 8-12 hours 1
- CrCl <20 mL/min: Avoid unless hemodialysis available 1
Pharmacokinetic Considerations
The half-life of imipenem extends significantly with renal dysfunction, reaching slightly greater than 4 hours in functionally anephric patients compared to 1 hour in normal volunteers 3. This prolonged half-life is controlled by a metabolic clearance pathway unaffected by cilastatin 3.
Important caveat: While imipenem clearance decreases with renal impairment, cilastatin accumulates more dramatically, with terminal half-lives reaching 16 hours in anephric patients 3. This differential accumulation necessitates dose and schedule alterations to prevent cilastatin buildup while maintaining therapeutic imipenem concentrations 3.
Hemodialysis Patients
For patients on hemodialysis, 500 mg every 12 hours is the most efficient schedule that maintains effective trough antibiotic activity 4. This dosing achieves:
- Mean peak imipenem concentrations of 29 ± 5 mcg/mL
- Mean trough concentrations of 10 ± 3 mcg/mL 4
Supplemental dosing: Administer 500 mg after each hemodialysis session, as both imipenem and cilastatin are well cleared by dialysis 3, 4.
Clinical Context for Mild-Moderate Infections
For skin and soft tissue infections (a common mild-moderate indication), intramuscular administration of 500 mg every 12 hours has demonstrated 82% cure rates with excellent tolerability 5. This regimen achieved mean peak serum levels of 10.7 mcg/mL and trough levels of 2.1 mcg/mL, which were higher than expected in healthy volunteers due to mild renal dysfunction in the patient population 5.
Monitoring and Safety
Seizure risk: The principal concern with imipenem is seizure development, occurring in 1-3% of patients, particularly in the setting of renal insufficiency and underlying CNS disease 6. This risk necessitates careful dose adjustment in renal impairment 6.
Renal clearance: Approximately 60-70% of plasma clearance occurs via renal excretion of unchanged drug when co-administered with cilastatin, involving both glomerular filtration and active tubular secretion 3.
Common Pitfalls
- Do not use standard dosing in any degree of renal impairment (CrCl <90 mL/min) as this increases seizure risk and cilastatin accumulation 1, 6
- Avoid in CrCl <15 mL/min without dialysis access within 48 hours 1
- Monitor for infusion-related nausea and vomiting, which are common adverse effects 6
- Extend dosing intervals rather than just reducing doses to prevent cilastatin accumulation while maintaining therapeutic imipenem levels 3