Meropenem Dosing in Melioidosis and CNS Infections
Yes, meropenem 2g every 8 hours is specifically used for CNS infections, but the standard dose for melioidosis is 1g every 8 hours, with higher doses (up to 2g every 8 hours) reserved for severe cases with CNS involvement or septic shock.
Melioidosis Dosing
Standard intensive phase treatment for melioidosis uses meropenem 1g (or 25 mg/kg) intravenously every 8 hours for at least 14 days. 1, 2, 3 This is the FDA-approved dosing for intra-abdominal infections and represents the established regimen for most melioidosis cases. 4
When to Escalate Dosing in Melioidosis
Higher doses may be warranted in specific circumstances:
- Septic shock or critical illness: Meropenem demonstrates superior outcomes compared to ceftazidime in severe sepsis, and some experts use 2g every 8 hours in these cases. 2, 3
- CNS involvement: When melioidosis affects the central nervous system, escalated dosing is necessary to achieve adequate CSF penetration. 1
- Therapeutic drug monitoring: A case report demonstrated that standard dosing achieved suboptimal levels in a patient with multisystem melioidosis, requiring dose escalation for clinical improvement. 5
Treatment duration must extend beyond 14 days for patients with extensive pulmonary disease, deep-seated abscesses, osteomyelitis, septic arthritis, or neurologic involvement. 1, 2
CNS Infection Dosing
For bacterial meningitis and serious gram-negative CNS infections, meropenem 2g every 8 hours is the appropriate dose. 6, 4 The FDA label specifically approves 2g every 8 hours for bacterial meningitis in pediatric patients (40 mg/kg up to 2g maximum), and this high-dose regimen is extrapolated to adults with CNS infections. 4
Rationale for Higher CNS Dosing
- CSF penetration: Higher doses are required because meropenem CSF concentrations are typically 10-20% of serum levels. 7
- Pharmacodynamic optimization: Prolonged infusions of high-dose meropenem (2g over 3 hours every 8 hours) have successfully treated gram-negative CNS infections by maintaining CSF concentrations above the MIC for virtually the entire dosing interval. 7
- Enterobacteriaceae meningitis: Guidelines specifically recommend meropenem 2g every 8 hours when Enterobacteriaceae are isolated from CSF. 6
Critical Dosing Considerations
Renal function profoundly impacts meropenem exposure and target attainment. 8 The standard 1g every 8 hours dosing achieves inadequate exposure in 48-52% of critically ill patients with normal to augmented renal clearance when targeting pathogens with MIC ≥2 mg/L. 8
Renal Adjustment Algorithm
For creatinine clearance:
- >50 mL/min: Use standard dosing (1g or 2g every 8 hours depending on indication)
- 26-50 mL/min: Reduce to every 12 hours
- 10-25 mL/min: Give half-dose every 12 hours
- <10 mL/min: Give half-dose every 24 hours 4
Common pitfall: Augmented renal clearance in critically ill patients can lead to subtherapeutic levels despite "normal" dosing. Consider therapeutic drug monitoring or extended infusions (over 3 hours) in septic patients with preserved renal function. 5, 8, 7