What meropenem dose should be given to a 65‑year‑old female with normal renal function, and how should it be adjusted for reduced creatinine clearance?

Meropenem Dosing for a 65-Year-Old Female

For a 65-year-old female with normal renal function (creatinine clearance >50 mL/min), administer meropenem 1 gram intravenously every 8 hours; however, if creatinine clearance is reduced, dose adjustments are mandatory to prevent drug accumulation and potential neurotoxicity. 1, 2

Standard Dosing in Normal Renal Function

• The standard dose is 1 gram IV every 8 hours for most serious infections in patients with creatinine clearance >50 mL/min 2, 3
• Peak plasma concentrations reach approximately 53-62 mg/L after 1 gram IV administration, with an elimination half-life of approximately 1 hour in patients with normal renal function 4, 5
• Up to 70% of meropenem is excreted unchanged in urine, making renal function the primary determinant of drug clearance 5

Age-Related Considerations

• Age alone does not require dose reduction in the absence of renal impairment, as clinical trials showed no overall differences in safety or effectiveness between elderly patients (≥65 years) and younger patients 2
• However, elderly patients are more likely to have age-associated reduction in creatinine clearance, which correlates directly with reduced meropenem plasma clearance 2
• Renal function declines by approximately 1% per year beyond age 30-40, meaning a 65-year-old may have lost 25-35% of baseline renal function even with "normal" serum creatinine 6

Critical Pitfall: Serum Creatinine Underestimates Renal Impairment in the Elderly

• Serum creatinine alone is unreliable in elderly patients and can appear falsely normal despite significantly reduced creatinine clearance 6
• Always calculate creatinine clearance using the Cockcroft-Gault formula before initiating meropenem therapy 6
• The Cockcroft-Gault formula is specifically recommended for drug dosing calculations in elderly patients 6

Dose Adjustments for Reduced Creatinine Clearance

When creatinine clearance falls below 50 mL/min, mandatory dose adjustments are required: 2, 4

• Creatinine clearance 26-50 mL/min: 1 gram IV every 12 hours 1, 2
• Creatinine clearance 10-25 mL/min: 500 mg IV every 12 hours 1, 2
• Creatinine clearance <10 mL/min: 500 mg IV every 24 hours 1, 2

The elimination half-life is prolonged up to 13.7 hours in anuric patients with end-stage renal disease, compared to 1 hour in healthy volunteers 4

Maintaining Full Dose While Extending Interval

• For moderate renal impairment, maintain the full 1 gram dose and extend the dosing interval to every 12 hours rather than reducing to 500 mg every 8 hours 1
• This approach preserves peak concentrations needed for optimal concentration-dependent bacterial killing while preventing drug accumulation 1
• The percentage of time that unbound plasma meropenem exceeds the pathogen's MIC is the pharmacodynamic parameter that best correlates with efficacy 2

Special Considerations for Resistant Organisms

• When treating infections with organisms having MIC ≥4-8 mg/L, use extended infusion over 3 hours even in renal impairment to maximize time above MIC 1
• For carbapenem-resistant Enterobacterales with meropenem MIC ≥8 mg/L, administer 1 gram over 3 hours every 8 hours (with appropriate renal dose adjustments) 1

Renal Replacement Therapy Dosing

For patients on intermittent hemodialysis:

• Approximately 50% of meropenem is removed by hemodialysis 1, 4
• Administer doses after dialysis sessions to prevent premature drug removal and ensure adequate exposure 1

For patients on continuous renal replacement therapy (CRRT):

• CRRT removes 25-50% of meropenem, while CVVHDF removes 13-53% 1, 4
• Recommended dose: 1 gram every 8-12 hours to compensate for continuous drug removal 1
• The elimination half-life during CVVH is approximately 8.7 hours 7

For patients on sustained low-efficiency dialysis (SLED):

• Maintain the full 1 gram dose every 12 hours to preserve concentration-dependent killing 1

Neurotoxicity Monitoring

• Maintain meropenem trough concentrations below 64 mg/L to minimize risk of neurotoxic adverse events 1
• Meropenem-related seizures are rare (0.1%), even in patients with renal impairment, and occur less frequently than with imipenem 8
• Routinely assess elderly patients for behavioral changes, delirium, hallucinations, agitation, and seizures to detect early neurotoxicity 1

Therapeutic Drug Monitoring

• Consider therapeutic drug monitoring in critically ill elderly patients with renal impairment to ensure adequate drug exposure and prevent toxicity 1
• This is particularly important for patients on renal replacement therapy where drug clearance is highly variable 1

Monitoring Renal Function During Therapy

• Monitor renal function indicators throughout treatment, though meropenem does not cause clinically significant changes in renal function 1, 8
• There is no clinically significant mean change in indicators of renal flux between baseline and end of treatment in elderly or renally impaired patients 8