Population Pharmacokinetics of Prolonged Infusion Meropenem in Cystic Fibrosis (CF) Children

• Meropenem Blood Concentrations [ Time Frame: 8 hours after 3rd meropenem dose ] [ Designated as safety issue: No ]
  Blood sampling for meropenem concentrations will occur at 4 time points after the third dosage: 3-3.5 hours, 4-5 hours, 5-6 hours, and 7-8 hours.
  
  
• Population Pharmacokinetics - Total Body Clearance [ Time Frame: 8 hours after 3rd meropenem dose ] [ Designated as safety issue: No ]
  Based on meropenem concentrations, the pharmacokinetics of the study population will be analyzed to determine each patient's total body clearance.
  
  
• Population Pharmacokinetics - Volume of Distribution [ Time Frame: 8 hours after 3rd meropenem dose ] [ Designated as safety issue: No ]
  Based on meropenem concentrations, the pharmacokinetics of the study population will be analyzed to determine each patient's volume of distribution.
  
  

• Safety [ Time Frame: 14-21 days ] [ Designated as safety issue: Yes ]
  This will be an intention to treat analysis of all 30 participants receiving meropenem as a 3 hour prolonged infusion. Participants will be monitored for any sign of symptom of adverse events throughout the course of the study. An adverse event will be defined as any pathologic or unintended change in the structure (signs), function (symptoms), or chemistry (laboratory values) of the body associated with the use of the study drug.
  
  
• Practicality of 3 Hour Prolonged Infusion [ Time Frame: 14-21 days ] [ Designated as safety issue: No ]
  This will be an intention to treat analysis of all 30 participants receiving meropenem as a 3 hour prolonged infusion. The Cystic Fibrosis Questionnaire-Revised (CFQ-R) will be utilized to assess patient or parent assessments of the burden of the prolonged infusion treatment. The CFQ-R will be administered at the beginning of the study and then within 7 days after completion of meropenem therapy.
  
  
• Meropenem Pharmacodynamics [ Time Frame: 14-21 days ] [ Designated as safety issue: No ]
  Meropenem exposures defined from the population model for each participant will be analyzed as a function of the isolated pathogens meropenem minimum inhbitory concentration (MIC) to define the exposure of meropenem associated with an absolute and relative percent change in the Forced Epiratory Volume (FEV1).
  
  

This study will be conducted at 3 pediatric hospitals in the United States (Columbia University Medical Center, New York, NY; University of North Carolina, Chapel Hill, NC; St. Christopher's Hospital for Children, Philadelphia, PA). Cystic Fibrosis children (age 6-17 years) admitted to one of these enrolling sites with an acute exacerbation of his or her pulmonary infection who require antibiotic therapy with meropenem will be eligible. Meropenem will be administered as a 3 hour prolonged infusion and blood concentrations will be measured to determine the population pharmacokinetics in 30 patients, the safety of prolonged infusion meropenem, and the practicality as measured be treatment burden using a questionaire. The population pharmacokinetic model developed will be utilized to determine the optimal dose of meropenem to administer to children with Cystic Fibrosis, and define an exposure response relationship for the drug in this population.