What is the recommended dose of meropenem for a 65kg middle-aged patient with severe asthma exacerbation, intubated, with acute kidney injury (AKI) and a creatinine level indicating impaired renal function, opioid abuse history, and diabetic ketoacidosis (DKA) on insulin, who has developed a high-grade fever?

Meropenem Dosing in AKI with Creatinine 190 µmol/L

For your 65kg patient with severe AKI (creatinine 190 µmol/L, approximately 2.15 mg/dL), give meropenem 500 mg IV every 12 hours. This dose accounts for his significantly reduced renal clearance while maintaining adequate plasma concentrations for bacterial coverage 1, 2, 3.

Calculating Creatinine Clearance

Your patient's estimated creatinine clearance is approximately 30-40 mL/min based on:

• Weight: 65 kg
• Creatinine: 190 µmol/L (2.15 mg/dL)
• This places him in moderate-to-severe AKI requiring dose adjustment 4

Recommended Dosing Regimen

Standard dose: 500 mg IV every 12 hours 2, 3

• Peak plasma concentrations will reach approximately 24-39 mg/L 2, 3
• Trough concentrations will be 3-7 mg/L, adequate for most susceptible organisms 2, 3
• Terminal elimination half-life extends to 6-9 hours in AKI (versus 1 hour in normal renal function) 2, 4, 3

Rationale for This Dose

Pharmacokinetic changes in AKI:

• Total meropenem clearance drops to approximately 52 mL/min in anuric patients (from 287 mL/min in healthy individuals) 2
• Nonrenal clearance becomes the primary elimination route at 30-35 mL/min 2, 3
• Volume of distribution remains relatively stable at 0.37 L/kg 3
• Elimination half-life increases 6-8 fold compared to normal renal function 1, 4

For creatinine clearance 30-50 mL/min:

• The dosing interval should be doubled from every 8 hours to every 12 hours 4
• The 500 mg dose maintains therapeutic levels without accumulation 2, 3

Alternative Dosing if Renal Function Worsens

If creatinine clearance drops below 30 mL/min:

• Reduce to 500 mg IV every 24 hours 4

If patient requires hemodialysis:

• Give 500 mg after each dialysis session 4
• Hemodialysis removes approximately 50% of meropenem 1

Special Considerations for This Patient

Opioid abuse history:

• Does not affect meropenem dosing or clearance 5
• No drug-drug interactions between meropenem and opioids 5

DKA on insulin:

• Meropenem does not affect glucose metabolism or insulin requirements 5
• Continue monitoring glucose closely per AKI guidelines (target 140-180 mg/dL) 6, 7
• Reduce insulin dose by 30-50% due to AKI to prevent hypoglycemia 7

Intubated with severe asthma:

• Meropenem has excellent penetration into respiratory tissues 5
• No dose adjustment needed for mechanical ventilation 5

Monitoring Parameters

Monitor the following during meropenem therapy:

• Serum creatinine daily to assess AKI trajectory 8
• Electrolytes every 6-12 hours (sodium, potassium, phosphate, calcium) given critical illness and AKI 6
• Clinical response to antibiotics within 48-72 hours 5
• Signs of seizures (rare at 0.1% even in renal impairment, but monitor) 9

Common Pitfalls to Avoid

Do not use standard dosing (1g every 8 hours) in this patient - this will lead to drug accumulation and potential toxicity given his reduced clearance 1, 4

Do not underdose - some sources recommend 250 mg doses, but critically ill patients with severe infections require 500 mg to achieve adequate peak concentrations 2, 3

Do not forget to adjust if renal function changes - if creatinine improves or worsens, reassess dosing interval 4

Avoid nephrotoxic agents - discontinue any NSAIDs, aminoglycosides, or other nephrotoxic drugs that could worsen his AKI 8