What is the recommended dosage of imipenem (Imipenem/Cilastatin) for a patient with cellulitis, Chronic Kidney Disease (CKD), and on Hemodialysis (HD)?

Imipenem Dosing for Cellulitis in CKD Patients on Hemodialysis

For a patient with cellulitis on hemodialysis, administer imipenem/cilastatin 500 mg every 12 hours, with each dose given immediately after dialysis sessions. 1, 2

Dosing Rationale

Standard Hemodialysis Regimen

• 500 mg every 12 hours is the most efficient schedule that maintains effective trough antibiotic activity in hemodialysis patients 2
• This dosing achieves imipenem peak concentrations of approximately 29 μg/mL and trough concentrations of 10 μg/mL, which are therapeutically adequate 2
• Alternative dosing of 250 mg every 6 hours or 500 mg every 6 hours has been studied, but 500 mg every 12 hours provides optimal efficacy with less frequent administration 2

Critical Timing Consideration

• Always administer imipenem/cilastatin immediately after hemodialysis sessions 3, 4, 5
• Both imipenem and cilastatin are efficiently removed during a 4-hour dialysis session 3
• Hemodialysis reduces the half-life of imipenem from 4.80 hours to 2.45 hours and cilastatin from 16.63 hours to 3.86 hours 5
• Post-dialysis dosing prevents premature drug removal and ensures adequate therapeutic levels 3, 4

Pharmacokinetic Considerations in ESRD

Imipenem Accumulation

• Imipenem does not accumulate with the recommended dosing schedule 2
• The plasma half-life of imipenem increases from 52 minutes in normal renal function to 173 minutes (approximately 3 hours) in end-stage renal failure 3
• Metabolic clearance pathways remain functional even in severe renal dysfunction, preventing excessive accumulation 4

Cilastatin Accumulation

• Cilastatin does accumulate between dialysis sessions in hemodialysis patients 2, 5
• Peak cilastatin concentrations average 89 μg/mL and trough concentrations 70 μg/mL 2
• The half-life of cilastatin increases dramatically from 54 minutes in normal subjects to 798 minutes (approximately 13 hours) in end-stage renal disease 3
• This accumulation is managed by the twice-daily dosing schedule and removal during dialysis 2

Maximum Dose Limitations

Severe Renal Impairment Restrictions

• For patients with creatinine clearance less than 15 mL/min (including hemodialysis patients), the maximum dose should be limited to either 1000 mg twice daily OR 500 mg four times daily 3
• The FDA label states that patients with creatinine clearance less than 15 mL/min should not receive imipenem/cilastatin unless hemodialysis is instituted within 48 hours 1
• For cellulitis specifically, the 500 mg every 12 hours regimen is appropriate and well-tolerated 2

Safety Monitoring

Seizure Risk

• Seizures occur in 1-3% of patients treated with imipenem and are more likely in the setting of renal insufficiency 6
• Monitor closely for neurological symptoms, particularly in patients with underlying CNS disease 6
• The recommended dosing schedule helps minimize this risk by preventing excessive drug accumulation 3

Other Adverse Effects

• Nausea and vomiting may occur during intravenous infusion 6
• Multiple-dose studies in hemodialysis patients for 2-14 days showed no notable clinical side effects with the 500 mg every 12 hours schedule 2

Clinical Efficacy for Cellulitis

• Imipenem has the broadest antibacterial spectrum of available systemic antibiotics, covering streptococci, methicillin-sensitive staphylococci, anaerobes, and common aerobic gram-negative nosocomial pathogens 6
• This broad coverage makes it appropriate for cellulitis, particularly in hemodialysis patients who may have polymicrobial or resistant organisms 6