Pharmacokinetics and Pharmacodynamics of Ceftazidime in Pediatric ICU Patients

Mortality benefit has been proven with early antibiotic administration in sepsis. Antimicrobial therapy should be based on early achievement of effective drug concentrations by optimizing the pharmacokinetic/pharmacodynamics of individual drugs. Optimal dosing in the critically ill patient can be challenging with the rapidly changing physiology of sepsis during the first days of hospitalization with capillary leak, fluid overload, changes in cardiac output, and alterations renal clearance. Ceftazidime is the preferred beta-lactam for empiric treatment of sepsis at Lurie Children's Hospital because of its anti-pseudomonal and anti-enteric bacilli coverage, however, the majority of pharmacokinetic data currently published in pediatrics does not include Intensive Care Unit (ICU) patients. Adult pharmacokinetic/pharmacodynamics data suggest that critically ill adults with high level of illness severity may benefit from continuous or extended infusion beta lactam therapy to optimize the therapeutic concentration particularly for pathogens that are relatively resistant to beta-lactams. Understanding the changing pharmacokinetic/pharmacodynamics of ceftazidime with the progression of illness in the ICU may help determine if current dosing regimens are adequate to maintain appropriate drug concentrations to optimize antimicrobial treatment.

Inclusion Criteria: * Admitted to pediatric or cardiac intensive care unit * Between the ages of 2 month to 18 years * Receiving ceftazidime for an anticipated course of greater than or equal to 48 hours * Central venous or arterial access for blood sampling Exclusion Criteria: * Less than 2 months or greater than 18 years * Anticipated need for renal replacement therapy or ECMO * History of chronic kidney disease greater than stage 1 * Inadequate access for blood draws