What is the recommended dosing of Ertapenem (a carbapenem antibiotic) for a patient with an Extended-Spectrum Beta-Lactamase (ESBL) infection and impaired renal function?

Renal Dosing of Ertapenem for ESBL Infection

For patients with ESBL infections and severe renal impairment (creatinine clearance ≤30 mL/min/1.73 m²), reduce ertapenem to 500 mg once daily; if administered within 6 hours before hemodialysis, give a supplementary 150 mg dose after the dialysis session. 1

Standard Dosing in Normal Renal Function

• Ertapenem 1 g IV once daily is the standard dose for ESBL infections in patients with creatinine clearance >30 mL/min/1.73 m², making it a preferred carbapenem option due to single daily administration and antimicrobial stewardship considerations. 2, 1

• The once-daily dosing regimen is particularly advantageous for outpatient parenteral antimicrobial therapy and is preferred over meropenem/imipenem for non-severe ESBL infections to reserve broader-spectrum carbapenems for critically ill patients. 2

Renal Dose Adjustments

Mild to Moderate Renal Impairment (CrCl >30 mL/min/1.73 m²)

• No dose adjustment is necessary when creatinine clearance exceeds 30 mL/min/1.73 m², as pharmacokinetic studies show only minimal accumulation (7% increase in AUC with mild impairment, 53% with moderate impairment). 1, 3

Severe Renal Impairment (CrCl ≤30 mL/min/1.73 m²)

• Reduce the dose to 500 mg once daily for patients with creatinine clearance ≤30 mL/min/1.73 m², including those with end-stage renal disease (CrCl ≤10 mL/min/1.73 m²). 1, 3

• This dose reduction is critical because pharmacokinetic studies demonstrate a 158% increase in drug exposure with advanced renal insufficiency and 192% increase in ESRD, with half-life prolonging from 4.5 hours to 14.1 hours. 3

Hemodialysis Patients

• If ertapenem 500 mg is administered within 6 hours prior to hemodialysis, give a supplementary 150 mg dose following the dialysis session to replace the approximately 30% of drug removed during dialysis. 1, 3

• If ertapenem is given at least 6 hours before hemodialysis, no supplementary dose is needed, as sufficient time has elapsed for drug distribution and the pre-dialysis dose accounts for expected clearance. 1

Critical Safety Considerations

CNS Toxicity Risk in Advanced Renal Failure

• Even the recommended 500 mg daily dose may cause severe neurotoxicity in patients with Stage 5 CKD, particularly those not yet on dialysis, manifesting as hallucinations, myoclonic jerks, seizures, and cognitive impairment lasting up to 2 weeks despite drug discontinuation. 4, 5

• Plasma ertapenem levels can reach 53.7 mg/L (far exceeding the therapeutic MIC90 of 2 mg/L) with the "reduced" 500 mg dose in advanced renal failure, due to ertapenem's high lipophilicity and CNS penetration. 4

• Consider further dose reduction or alternative antibiotics in Asian patients or those with small body size on hemodialysis, as the standard 500 mg dose has caused CNS toxicity after only 3-7 consecutive doses in this population. 5

• High-flux hemodialysis does not rapidly clear ertapenem due to its large volume of distribution and lipophilicity, meaning neurologic symptoms persist for approximately 2 weeks even after drug cessation and dialysis initiation. 4

Clinical Efficacy Considerations in Renal Impairment

Impact of Renal Function on Treatment Response

• In patients with renal insufficiency (CrCl <50 mL/min) and alkaline urinary pH, time to negative urine cultures is prolonged (>3 days) compared to those with acid urine (<3 days), though bacteriologic cure is ultimately achieved. 6

• Despite delayed clearance, ertapenem remains highly effective for ESBL urinary tract infections in patients with renal impairment, particularly when urinary pH is acidic. 6

Practical Dosing Algorithm

1. Calculate creatinine clearance using the Cockcroft-Gault equation: Males: (weight in kg) × (140-age) / (72 × serum creatinine); Females: 0.85 × male value. 1

2. For CrCl >30 mL/min/1.73 m²: Give standard dose of 1 g IV once daily. 1

3. For CrCl ≤30 mL/min/1.73 m²: Reduce to 500 mg IV once daily. 1

4. For hemodialysis patients:

   • If dosing <6 hours before dialysis: Give 500 mg, then 150 mg supplemental dose post-dialysis. 1
   • If dosing ≥6 hours before dialysis: Give 500 mg only, no supplement needed. 1

5. Monitor closely for CNS toxicity (confusion, hallucinations, myoclonus, seizures) in all patients with CrCl <30 mL/min, especially those not yet on dialysis or with small body habitus. 4, 5

Key Pitfalls to Avoid

• Do not use the full 1 g dose in patients with CrCl ≤30 mL/min, as this leads to dangerous drug accumulation and high risk of neurotoxicity. 1, 3

• Do not assume the 500 mg dose is always safe in advanced renal failure—consider even lower doses or alternative agents in high-risk patients (Stage 5 CKD not on dialysis, small body size, elderly). 4, 5

• Do not forget the post-dialysis supplemental dose when ertapenem is given within 6 hours of hemodialysis, as 30% of the drug is removed. 1, 3

• Do not mix or co-infuse ertapenem with other medications, and do not use diluents containing dextrose, as per FDA labeling requirements. 1