What meropenem dosing regimen should be used in an adult patient based on creatinine clearance, including adjustments for renal impairment, intermittent hemodialysis, continuous renal replacement therapy, and severe infections such as meningitis or ventilator‑associated pneumonia?

Meropenem Dosing Based on Creatinine Clearance

For adult patients with normal renal function (CrCl >50 mL/min), administer meropenem 1–2 g IV every 8 hours; as creatinine clearance declines, reduce both dose and frequency systematically, with patients on intermittent hemodialysis receiving 500 mg every 24 hours (given after dialysis), while those on continuous renal replacement therapy require 500 mg every 8–12 hours depending on residual urine output.

Standard Dosing for Normal Renal Function

• Adults with CrCl >50 mL/min should receive 1 g IV every 8 hours for most serious infections, including complicated intra-abdominal infections, pneumonia, and skin/soft tissue infections 1.
• For severe infections or meningitis, increase to 2 g IV every 8 hours to achieve adequate CNS penetration and maintain bactericidal concentrations 1.
• The elimination half-life in healthy volunteers is approximately 1 hour, necessitating frequent dosing to maintain therapeutic levels 1.

Renal Impairment Dosing Algorithm

Moderate Renal Impairment (CrCl 26–50 mL/min)

• Reduce dose to 1 g IV every 12 hours for standard infections 1.
• For meningitis or severe infections, use 2 g IV every 12 hours 1.

Severe Renal Impairment (CrCl 10–25 mL/min)

• Administer 500 mg IV every 12 hours for most infections 1.
• For meningitis, increase to 1 g IV every 12 hours 1.

End-Stage Renal Disease (CrCl <10 mL/min)

• Give 500 mg IV every 24 hours in anuric patients not receiving renal replacement therapy 1.
• The elimination half-life extends dramatically to 13.7 hours in anuric patients with end-stage renal disease, justifying once-daily dosing 1.

Intermittent Hemodialysis Dosing

• Administer 500 mg IV after each hemodialysis session, as approximately 50% of meropenem is removed during a standard 4-hour dialysis run 1, 2.
• Timing is critical: give the dose post-dialysis to avoid premature drug removal and subtherapeutic concentrations 1.
• For severe infections in hemodialysis patients, consider 1 g post-dialysis if treating organisms with higher MICs 3.

Continuous Renal Replacement Therapy (CRRT) Dosing

Impact of CRRT Modality on Drug Clearance

• CVVHF (continuous venovenous hemofiltration) removes 25–50% of meropenem, while CVVHDF (continuous venovenous hemodiafiltration) eliminates 13–53% depending on ultrafiltrate and dialysate flow rates 1.
• The sieving coefficient is approximately 0.93, indicating nearly complete passage across the hemofilter membrane 3.

Standard CRRT Dosing Recommendations

• For patients on CVVHF or CVVHDF with ultrafiltrate/dialysate rates of 1–3 L/hr, administer 1 g IV every 12 hours 3.
• This regimen maintains serum concentrations above 4 mg/L (the MIC90 for Pseudomonas aeruginosa) for approximately 67% of the dosing interval 3.

Adjusting for Residual Diuresis

• Residual urine output is the most important determinant of meropenem clearance in CRRT patients, with a 5-fold difference in clearance between patients with residual CrCl >50 mL/min versus <10 mL/min 4.
• Oligoanuric patients (minimal residual diuresis) require 500 mg IV every 8 hours as a 30-minute infusion to achieve 40% time above MIC for susceptible organisms (MIC ≤2 mg/L) 4.
• Patients with preserved diuresis (>500 mL/24 hours) need the same 500 mg dose given as a 3-hour extended infusion to maintain adequate drug exposure 4.

Treating Resistant Organisms on CRRT

• For bacteria with MICs of 2–4 mg/L (near the resistance breakpoint), increase frequency to 500 mg every 6 hours 4.
• Oligoanuric patients can receive this as a 30-minute bolus, while those with preserved diuresis require 3-hour extended infusions 4.
• If targeting 100% time above MIC (for immunocompromised patients or severe sepsis), use extended infusions regardless of residual renal function 4.

Special Considerations for Meningitis

• Meningitis requires higher doses (2 g IV every 8 hours in normal renal function) due to limited CNS penetration 1.
• In renal impairment with CrCl 26–50 mL/min, use 2 g every 12 hours; for CrCl 10–25 mL/min, use 1 g every 12 hours 1.
• On CRRT, consider 1 g every 8–12 hours depending on ultrafiltrate rates and residual diuresis to ensure adequate CSF concentrations 5.

Critical Monitoring Parameters

• Measure actual creatinine clearance using 24-hour urine collection rather than relying solely on estimated GFR, especially in critically ill patients with fluctuating renal function 6.
• Assess residual urine output in CRRT patients to guide dose titration—this is an inexpensive and practical tool for optimizing therapy 4.
• Monitor for seizures in patients with renal impairment, as accumulation of meropenem increases neurotoxicity risk, particularly when doses are not appropriately reduced 1.

Common Pitfalls to Avoid

• Do not use standard renal dosing tables for CRRT patients—CRRT clearance varies widely (13–53%) based on modality and flow rates, requiring specific CRRT-based dosing 1.
• Avoid giving meropenem before hemodialysis, as this results in significant drug removal and treatment failure 1.
• Do not underdose in CRRT due to fear of toxicity—meropenem has an excellent tolerability profile, and underdosing is more dangerous than modest overdosing in severe infections 1.
• Recognize that CRRT intensity (ultrafiltrate rate) was not identified as a significant clearance modifier in recent population PK studies—residual diuresis matters more 4.