The methodology and pharmacokinetics study of intraventricular administration of vancomycin in patients with intracranial infections after craniotomy

J Crit Care. 2015 Feb;30(1):218.e1-5. doi: 10.1016/j.jcrc.2014.09.020. Epub 2014 Oct 2.

Abstract

Objective: The purpose of the study was to investigate the pharmacokinetics of combined intravenous (i.v.) and intracerebroventricular (i.c.v.) vancomycin for patients with intracranial infections after craniotomy and to provide the basis for establishing the intracranial local administration criterion.

Methods: Fourteen postoperative intracranial infection cases with surgical cavity/ventricular drainages were given vancomycin (1.0 g, i.v. drip for 2 hours, quaque 12 h, and a simultaneous i.c.v. injection of 10 mg). Their blood and cerebral spinal fluid (CSF) specimens were collected at each time point before and after administrations. The concentrations and biochemical properties were measured.

Results: The 1-hour serum vancomycin concentration reached a peak of 46.38 ± 33.39 mg/L; the trough concentration of 48 hours was 8.10 ± 7.11 mg/L; the CSF vancomycin concentration reached a peak of 382.17 ± 421.00 mg/L at 0.25 hours, and the 48-hour trough concentration was 30.82 ± 29.53 mg/L. The inhibitory quotient was calculated at 15.4 by the minimum inhibitory concentration 2 mg/L of target bacteria and had reached the range of 10 to 20 recommended by Infectious Diseases Society of America guidelines. The pH value and osmotic pressure of CSF were found to have no significant changes before and after administration. There was no increasement of seizures and ototoxicity in our study. Before the drug administration and 1 week later, the changes of creatine had no statistically significant, with P > .05.

Conclusions: The combined i.v. and i.c.v. administration may improve CSF vancomycin concentrations without side effects at the same dosage. Our finding suggests that it can be an option for the treatment of severe intracranial infections after craniotomy; however, its safety and effectiveness need to be confirmed by further large-scale studies.

Keywords: Intracranial infection; Intraventricular administration; Pharmacokinetics; Surgical site infection of neurosurgery; Vancomycin.

MeSH terms

  • Adult
  • Aged
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / cerebrospinal fluid
  • Anti-Bacterial Agents / pharmacokinetics*
  • Central Nervous System Bacterial Infections / blood*
  • Central Nervous System Bacterial Infections / cerebrospinal fluid*
  • Central Nervous System Bacterial Infections / drug therapy
  • Cerebrospinal Fluid Pressure / drug effects
  • Craniotomy / adverse effects*
  • Female
  • Humans
  • Hydrogen-Ion Concentration
  • Infusions, Intravenous
  • Injections, Intravenous / methods
  • Injections, Intraventricular / methods
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Time Factors
  • Vancomycin / administration & dosage*
  • Vancomycin / adverse effects
  • Vancomycin / blood
  • Vancomycin / cerebrospinal fluid
  • Vancomycin / pharmacokinetics*
  • Young Adult

Substances

  • Anti-Bacterial Agents
  • Vancomycin