Clinical Trial: Daptomycin in Pediatric Patients With Bacterial Meningitis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Evaluation of Cerebrospinal Fluid Concentration of Daptomycin (Cubicin¬) in Pediatric Patients With Gram-positive Bacterial Meningitis, Concurrently Receiving Standar

Brief Summary: 5 Children > 3months and < 16 years with Gram-positive meningitis will receive a single dose of daptomycin 24 hours after the first dose of ceftriaxone. 4-8 hours after daptomycin administration a second lumbar puncture is performed to determine the peak concentration of daptomycin in the cerebrospinal fluid. In parallel peak and trough level of daptomycin will be measured in the plasma. The investigators anticipate that daptomycin penetrates into the cerebrospinal fluid in bactericidal concentrations

Detailed Summary:

Background

Acute bacterial meningitis is a severe infection, which leads to persistent neurological deficits in up to 50% of patients, despite optimal medical treatment. Although, the incidence of acute bacterial meningitis has declined in developed countries since the advent of vaccines against Haemophilus influenzae and Streptococcus pneumoniae, this is not yet true for developing countries. Also, the impact of serotype replacement in invasive pneumococcal disease cannot be estimated to date.

Acute bacterial meningitis causes brain injury most prominently in the cerebral cortex, the inner ear and in the hippocampus. In the hippocampus, a brain region functionally important for learning and memory, the brain damage is characterized by apoptosis of cells in the hippocampal dentate gyrus. Autopsy studies demonstrated the occurrence of apoptosis in neurons of the hippocampal dentate gyrus in the majority (> 75%) of human autopsy cases, who died of acute bacterial meningitis. Children are particularly vulnerable to this form of brain damage because of ongoing development of neurological functions and they have a higher risk of neurologic deficits after bacterial meningitis than adults. The 3 most common pathogens in childhood meningitis are Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis. Streptococcus pneumoniae is associated with the greatest risk for fatal outcome or persistent neurological deficits. In the most recent prospective study hearing loss was the most common major sequelae in half of the patients, followed by cognitive deficits (40.0%), seizures (21.2%), and motor deficits (21.2%); one third of these patients had multiple defects.The pathogenesis of brain damage in meningitis is driven by the host's owns inflammatory reaction to the invading pathogens in the subarachnoid space. Thi
Sponsor: University Hospital Inselspital, Berne

Current Primary Outcome: Characterization of the peak concentration of daptomycin in the cerebrospinal fluid of pediatric patients with bacterial meningitis [ Time Frame: 4-8 hours after drug administration ]

Original Primary Outcome: Same as current

Current Secondary Outcome: Evaluate possible side effects of daptomycin in pediatric patients with bacterial meningitis [ Time Frame: 2 years ]

Original Secondary Outcome: Same as current

Information By: University Hospital Inselspital, Berne

Dates:
Date Received: January 26, 2012
Date Started: April 2012
Date Completion: April 2018
Last Updated: December 10, 2015
Last Verified: December 2015