What is the recommended dose of ertapenem (generic name) for a hemodialysis (HD) patient with an infected wound caused by Proteus mirabilis and impaired renal function?

Ertapenem Dosing for Hemodialysis Patients with Proteus mirabilis Wound Infection

For hemodialysis patients with Proteus mirabilis wound infections, administer ertapenem 500 mg once daily, with a supplementary dose of 150 mg if given within 6 hours prior to hemodialysis. 1

FDA-Approved Dosing for Hemodialysis Patients

The FDA prescribing information provides clear guidance for ertapenem dosing in end-stage renal disease:

• Standard HD dose: 500 mg daily (reduced from the normal 1 gram dose) 1
• Timing consideration: If ertapenem is administered within 6 hours before hemodialysis, give a supplementary dose of 150 mg following the dialysis session 1
• No supplementation needed: If ertapenem is given at least 6 hours prior to hemodialysis 1

Clinical Efficacy for Proteus mirabilis Infections

Ertapenem demonstrates strong efficacy against Proteus mirabilis, including ESBL-producing strains:

• A case series showed 91% clinical efficacy for ESBL-producing Proteus mirabilis infections, with 85.7% microbiologic cure rates 2
• Wound infections specifically showed excellent outcomes, with all patients achieving clinical cure 2
• Ertapenem is appropriate for consolidation therapy after initial treatment with other agents 2

Critical Safety Warnings for HD Patients

The recommended 500 mg daily dose carries significant risk of central nervous system (CNS) toxicity in hemodialysis patients, despite being the FDA-approved dose. Multiple case reports document severe neurotoxicity:

• CNS toxicity manifestations: Seizures, hallucinations (auditory and visual), acute confusional states, asterixis, myoclonic jerks, and cognitive impairment 3, 4, 5
• Onset timing: Symptoms typically develop after 3-7 consecutive doses of the recommended 500 mg daily regimen 5
• Duration of toxicity: Neurologic symptoms can persist for 8-14 days after discontinuation, even with high-flux hemodialysis 3, 4
• Mechanism: Ertapenem's high lipophilicity and CNS penetration, combined with large volume of distribution, leads to sustained neurotoxicity that is poorly cleared by dialysis 4

Practical Dosing Algorithm

Given the documented toxicity risk, consider this approach:

1. Initial dosing: Start with 500 mg daily as per FDA guidance, administered after hemodialysis 1
2. Add supplemental dose: Give 150 mg post-dialysis if the daily dose was within 6 hours of HD 1
3. Monitor closely: Watch for early signs of CNS toxicity (confusion, hallucinations, myoclonus) starting after 3-4 doses 5
4. Consider dose reduction: The standard 500 mg dose may be excessive, particularly in patients with smaller body size 5
5. Duration: Limit treatment duration when possible, as toxicity risk increases with consecutive dosing 5

Key Clinical Pitfalls

• Hemodialysis removes only 30% of ertapenem per session, leading to significant drug accumulation with daily dosing 5
• Plasma levels can reach 53.7 mg/L (far exceeding the therapeutic MIC90 of 2 mg/L) even with dose-adjusted regimens 4
• High-flux hemodialysis does not adequately prevent or treat neurotoxicity once it develops 4
• Asian patients may be at higher risk due to relatively smaller body size 5
• Complete symptom resolution requires 8-14 days after drug discontinuation, necessitating prolonged monitoring 3, 4

Alternative Considerations

If CNS toxicity develops or high risk is identified, alternative carbapenems with better dialysis clearance profiles should be considered, though ertapenem remains effective for Proteus mirabilis when tolerated 2.