What is the recommended dose of Meropenem (Meropenem) for a 60-year-old male with severe impaired renal function (creatinine level of 6.6)?

Meropenem Dosing in Severe Renal Impairment

For a 60-year-old male with a creatinine of 6.6 mg/dL (indicating severe renal impairment with creatinine clearance <10 mL/min), meropenem should be dosed at 500 mg every 24 hours for complicated skin and skin structure infections, or 1 gram every 24 hours for intra-abdominal infections. 1

Creatinine Clearance Assessment

• A serum creatinine of 6.6 mg/dL in a 60-year-old male indicates severe renal impairment with an estimated creatinine clearance well below 10 mL/min 1
• The Cockcroft-Gault equation should be used to estimate creatinine clearance for drug dosing calculations in this patient 2
• Direct measurement of creatinine alone is insufficient to evaluate renal function, particularly in elderly patients 2

FDA-Approved Dosing for Severe Renal Impairment

The FDA label provides explicit dosing recommendations based on creatinine clearance: 1

• Creatinine clearance <10 mL/min: One-half the recommended dose every 24 hours 1
• For complicated skin and skin structure infections: 500 mg every 24 hours (half of the standard 1 gram dose) 1
• For intra-abdominal infections: 1 gram every 24 hours (half of the standard 2 gram daily dose) 1
• When treating Pseudomonas aeruginosa infections in skin/soft tissue: 500 mg every 24 hours (half of the standard 1 gram dose) 1

Administration Method

• Administer as an intravenous infusion over 15-30 minutes 1
• Alternatively, can be given as an intravenous bolus injection (5-20 mL) over 3-5 minutes 1

Pharmacokinetic Rationale

• Meropenem is primarily excreted unchanged by the kidneys, with approximately 70% of the dose excreted unchanged within 12 hours 1
• The elimination half-life increases dramatically from approximately 1 hour in patients with normal renal function to 7-13.7 hours in anuric patients with end-stage renal disease 3, 4
• In patients with creatinine clearance <30 mL/min, the half-life extends to approximately 5 hours 4
• Plasma clearance of meropenem correlates directly with creatinine clearance 1

Critical Monitoring Considerations

• Renal function should be monitored regularly during treatment in patients with severely impaired renal function 5
• Dosing intervals must be strictly adhered to in order to avoid excessive drug accumulation 5
• Peak plasma concentrations after standard dosing in severe renal impairment can reach levels similar to those in patients with normal renal function, but trough levels remain elevated for prolonged periods 3, 4

Hemodialysis Considerations

• If this patient requires hemodialysis, meropenem is readily dialyzable with approximately 50% of the drug removed during intermittent hemodialysis 3
• Hemodialysis shortens the elimination half-life from approximately 7 hours to 2.9 hours 4
• Dosing after each hemodialysis session is recommended for patients receiving intermittent hemodialysis 4
• For continuous renal replacement therapy (CRRT), dosing requirements may differ and should be adjusted based on the specific modality 3, 6, 7

Common Pitfalls to Avoid

• Do not use standard dosing (1 gram every 8 hours) in this patient - this will lead to dangerous drug accumulation given the severely impaired renal clearance 1
• Do not rely on serum creatinine alone without calculating creatinine clearance, as this underestimates the degree of renal impairment, especially in elderly patients 2
• Avoid underdosing by failing to account for the infection type - intra-abdominal infections require higher doses (1 gram every 24 hours) compared to skin infections (500 mg every 24 hours) 1
• Do not assume the patient is on dialysis without confirmation - non-dialyzed patients with severe renal impairment require the every 24-hour dosing schedule 1, 4

Target Attainment Considerations

• The pharmacokinetic/pharmacodynamic target for meropenem efficacy is the percentage of time that unbound plasma concentration exceeds the minimum inhibitory concentration (MIC) of the infecting organism 1
• With severe renal impairment and appropriate dose reduction, adequate trough concentrations can be maintained to achieve target attainment for most pathogens with MIC ≤2 mg/L 8, 4
• For infections with pathogens having MIC values ≥8 mg/L, even adjusted dosing may not achieve adequate efficacy targets in patients with severe renal impairment 8, 7