What is the management for Meropenem (Merrem) toxicity?

Management of Meropenem Toxicity

For meropenem overdose or toxicity, immediately discontinue the drug and provide symptomatic supportive care; hemodialysis effectively removes meropenem and should be considered in severe cases, particularly in patients with renal impairment. 1

Immediate Management

Drug Discontinuation and Supportive Care

• Stop meropenem immediately upon recognition of toxicity, as adverse events are generally mild and resolve with withdrawal or dose reduction 1
• Provide symptomatic treatment tailored to the specific manifestations of toxicity 1
• Monitor for resolution of symptoms, which typically occurs rapidly after discontinuation 1

Hemodialysis Considerations

• Meropenem and its metabolite are readily dialyzable and effectively removed by hemodialysis 1
• Consider hemodialysis in severe overdose cases, especially in patients with renal impairment where drug accumulation is more likely 1
• Approximately 50% of meropenem is eliminated by intermittent hemodialysis 2
• In individuals with normal renal function, rapid renal elimination occurs naturally 1

Neurological Toxicity Management

Recognition and Risk Factors

• Neurological toxicity is the most concerning manifestation of meropenem toxicity, presenting as acute confusional state, encephalopathy, myoclonus, seizures, or status epilepticus 3
• The main risk factor is renal failure, which causes rapid drug accumulation 3
• Meropenem has a relative pro-convulsive activity of 16 (compared to penicillin G = 100), making it less neurotoxic than cefepime or cefazolin but still clinically significant 3

Concentration Thresholds

• Trough concentrations above 64 mg/L for meropenem have been associated with neurotoxicity in 50% of ICU patients 3
• When the free minimum concentration normalized to MIC (fCmin/MIC ratio) exceeds 8, approximately two-thirds of ICU patients treated with meropenem experience significant neurological deterioration 3
• Temporarily suspend meropenem administration in patients with unexplained neurological manifestations and consider therapeutic drug monitoring 3

Special Populations

Renal Impairment

• Patients with renal insufficiency are at highest risk for meropenem accumulation and toxicity 1, 2
• The half-life of meropenem (approximately 1 hour in healthy volunteers) is prolonged up to 13.7 hours in anuric patients with end-stage renal disease 2
• Dosage adjustments are necessary in patients with creatinine clearance ≤50 mL/min to prevent toxicity 1

Continuous Renal Replacement Therapy (CRRT)

• Approximately 25-50% of meropenem is eliminated by continuous venovenous hemofiltration (CVVHF) 2
• Between 13-53% is eliminated by continuous venovenous hemodiafiltration (CVVHDF) 2
• These variations demonstrate the significant influence of treatment modality on drug elimination 2

Alternative Antibiotic Selection After Toxicity

For Suspected Multidrug-Resistant Organisms

• If meropenem was being used for suspected carbapenem-resistant organisms, switch to ceftazidime/avibactam 2.5 g IV every 8 hours 4
• For intra-abdominal infections with Pseudomonas risk, use ceftolozane/tazobactam 1.5 g IV every 8 hours plus metronidazole 500 mg every 6 hours 5
• Avoid rechallenging with meropenem or other carbapenems after toxicity, particularly in critically ill patients 4

For High-Risk Febrile Neutropenia

• Switch to cefepime 2 g IV every 8 hours or piperacillin/tazobactam 4.5 g IV every 6 hours 4
• Add vancomycin 15-20 mg/kg IV every 8-12 hours if catheter-related infection, skin/soft tissue infection, or hemodynamic instability is present 4

Common Pitfalls

• Do not underestimate the risk of neurotoxicity in patients with preserved renal function, as toxicity can occur even with appropriate dosing 3
• Avoid assuming that normal renal function eliminates the need for monitoring in critically ill patients receiving high doses 3
• Do not rechallenge with meropenem after documented toxicity, especially neurological toxicity, as recurrence is likely 4
• Be aware that meropenem-induced liver injury can occur, presenting with a mixed hepatocellular/cholestatic pattern that resolves with drug discontinuation 6