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Published on: December 4, 2017
Cerebrospinal fluid penetration of very high-dose meropenem: a case report
Thomas Kerz1, Friederike D von Loewenich2, Jason Roberts3,4,5,6
1Department of Neurosurgery, University Medical Center, Langenbeckstr. 1, 55131, Mainz, Germany. kerz@uni-mainz.de.
Background:
Standard dosing of meropenem (2 g t.i.d.) produces CSF concentrations of only 1-2 mg/L which is inferior to the clinical breakpoint for most Gram-negative bacteria. There is therefore concern that dosing must be increased in order to achieve therapeutic CSF concentrations for bacteria with susceptibility close to clinical breakpoints. Yet, the effects of high-dose meropenem on CSF concentrations are not well described in literature. We therefore determined meropenem CSF-levels in a patient who was treated with 15 g/day of meropenem.
Case Presentation:
Our patient suffered from a brain trauma and an external ventricular drainage was implanted. Later, a carbapenemase-producing Acinetobacter baumannii (OXA-23, NDM-1) was isolated from blood cultures and CSF. The MIC for meropenem was > 32 mg/L (R), and we opted for a combination therapy of meropenem, colistin and fosfomycin. Meropenem was given at an unusual high-dose (15 g/day) with the aim of achieving high CSF concentrations. CSF concentrations peaked at 64 mg/L. Yet, the patient succumbed to an intracranial bleed into a preexisting cerebral contusion.
Conclusions:
High-dose meropenem can achieve CSF levels largely superior to those achieved with commonly recommended dosing regimens. Though our patient succumbed to an intracranial bleed which could be regarded as a severe adverse event, we suggest that meropenem dosing can be increased when pathogens with increased MICs are found in the CSF. More in vivo data are however needed to determine the safety of high-dose meropenem.
Insights
High-dose meropenem therapy can achieve significantly higher cerebrospinal fluid (CSF) concentrations than standard dosing. This approach may be beneficial for treating difficult Gram-negative bacterial infections, but further safety data are needed.
Area of Science:
- Neuroscience
- Infectious Diseases
- Pharmacology
Background:
- Standard meropenem dosing (2 g t.i.d.) results in suboptimal cerebrospinal fluid (CSF) concentrations (1-2 mg/L), below clinical breakpoints for many Gram-negative bacteria.
- Increased meropenem dosing is a potential strategy to achieve therapeutic CSF concentrations against resistant pathogens.
- Limited literature exists on the CSF penetration and effects of high-dose meropenem therapy.
Observation:
- A patient with brain trauma and an external ventricular drain developed meningitis due to carbapenemase-producing Acinetobacter baumannii (OXA-23, NDM-1).
- The isolate exhibited high meropenem minimum inhibitory concentration (MIC) >32 mg/L, necessitating combination therapy.
- Meropenem was administered at a high dose of 15 g/day to maximize CSF penetration.
Findings:
- High-dose meropenem (15 g/day) achieved peak CSF concentrations of 64 mg/L.
- These concentrations are substantially higher than those typically observed with standard dosing regimens.
- Despite high meropenem levels, the patient experienced a fatal intracranial bleed.
Implications:
- Elevated meropenem dosing can achieve superior CSF concentrations, potentially improving treatment outcomes for severe CNS infections.
- The observed intracranial bleed highlights a potential severe adverse event associated with high-dose meropenem, warranting cautious use.
- Further in vivo studies are crucial to establish the safety profile and optimal dosing strategies for high-dose meropenem in treating central nervous system infections.
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