Pharmacokinetics and Safety of Meropenem in Infants Below 90 Days of Age With Probable and Confirmed Meningitis

Pharmacokinetics and Safety of Meropenem in Infants Below 90 Days of Age (Inclusive) With Probable and Confirmed Meningitis: A European Multicenter Phase I-II Trial

This phase I-II multicenter international trial is designed to study the pharmacokinetics of meropenem and to characterize the safety profile of meropenem in the treatment of infants ≤ 90 days of postnatal age with probable or confirmed bacterial meningitis.

The primary objective will be to study the pharmacokinetics (plasma and cerebrospinal fluid) of meropenem in infants ≤ 90 days of postnatal age with probable or confirmed bacterial meningitis and to characterize the safety profile of meropenem in the treatment of infants ≤ 90 days of postnatal age with probable or confirmed bacterial meningitis.

The secondary objectives are :

• To describe the efficacy of meropenem on day 3, at end of allocated treatment (EOAT), at test of cure (TOC) and at follow up (FU).
• To evaluate survival at FU
• To evaluate further episodes of meningitis (relapse or new infection) occurring between TOC and FU visits
• To define the organisms causing neonatal meningitis
• To describe the antibacterial susceptibility of meningitis-causing organisms and to describe the clinical and microbiological response according to this
• To evaluate mucosal colonization by resistant organisms before and after treatment with meropenem
• To evaluate bacterial eradication
• To evaluate functional genetic parameters that may affect response to therapy

Inclusion Criteria:

• Informed consent form signed by the parents/carers

• Chronological age below 90 days inclusive

• The presence of:

  • clinical signs consistent with BM (hyperthermia or hypothermia or temperature instability PLUS 1 or more neurological findings among coma, seizures, neck stiffness, apnoea, bulging fontanelle),
  • OR CSF pleocytosis (≥ 20 cells/mm3)
  • OR a positive Gram stain of CSF.

Exclusion Criteria:

• Presence of a CSF device
• Proven viral or fungal meningitis
• Severe congenital malformations if the infant is not to expect to survive for more than 3 months
• Other situations where the treating physician considers a different empiric antibiotic regimen necessary
• Known intolerance or contraindication to the study medication
• Participation in any other clinical study of an investigational medicinal product
• Renal failure and requirement of haemofiltration or peritoneal dialysis
• Meningitis with an organism known to be resistant to meropenem