Evaluation of Meropenem Penetration into Cerebrospinal Fluid in Patients with Meningitis After Neurosurgery

World Neurosurg. 2017 Feb:98:525-531. doi: 10.1016/j.wneu.2016.11.040. Epub 2016 Nov 17.

Abstract

Objective: Meropenem is important for management of postneurosurgical meningitis, but the data about its penetration into cerebrospinal fluid (CSF) are inadequate. This prospective, open-label study investigated the pharmacokinetic profile of meropenem in patients with postneurosurgical meningitis, especially its CSF penetration.

Methods: A total of 82 patients with postneurosurgical meningitis were included to receive meropenem intravenously according to a regimen of 2 g every 8 hours, 1 g every 8 hours, or 1 g every 6 hours. After infusion of 4 doses, blood and CSF samples were collected simultaneously at predefined time points. The high-performance liquid chromatography ultraviolet method was used to determine the concentration of meropenem.

Results: The peak meropenem concentration in blood and CSF was 43.2 ± 5.3 and 2.4 ± 0.3 mg/L in the group who received 2 g every 8 hours; 28.9 ± 2.7 and 1.2 ± 0.2 mg/L in the group who received 1g every 8 hours; and31.5 ± 3.4 and 1.6 ± 0.2 mg/L in the group who received 1g every 6 hours. The maximal percent penetration into CSF was 17.6% ± 7.3%, 14.3% ± 1.7%, and 30.9% ± 24.2%, respectively.

Conclusions: Dosing regimens of meropenem 1 g every 6 hours and 2 g every 8 hours provided higher CSF penetration than 1 g every 8 hours. A higher dose and shorter dosing interval of meropenem may be more useful for clearance of pathogens.

Keywords: Cerebrospinal fluid; Meropenem; Nosocomial infection; Penetration; Postneurosurgical meningitis.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / cerebrospinal fluid
  • Area Under Curve
  • Female
  • Gram-Negative Bacteria / isolation & purification
  • Gram-Negative Bacterial Infections / drug therapy
  • Humans
  • Male
  • Meningitis, Bacterial / drug therapy*
  • Meropenem
  • Microbial Sensitivity Tests
  • Middle Aged
  • Neurosurgical Procedures / adverse effects
  • Postoperative Complications / drug therapy
  • Prospective Studies
  • Thienamycins / blood
  • Thienamycins / cerebrospinal fluid
  • Thienamycins / pharmacokinetics*
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Thienamycins
  • Meropenem