Ceftaroline for Suspected or Confirmed Invasive Methicillin-Resistant Staphylococcus aureus: A Pharmacokinetic Case Series

Objectives: To describe the ceftaroline pharmacokinetics in critically ill children treated for suspected or confirmed methicillin-resistant Staphylococcus aureus infections, including blood stream infection and describe the microbiological and clinical outcomes. Design: Retrospective electronic medical record review. Settings: Free-standing tertiary/quaternary pediatric children's hospital. Patients: Critically ill children receiving ceftaroline monotherapy or combination therapy for suspected or confirmed methicillin-resistant S. aureus infections in the PICU. Intervention: None. Measurements and Main Results: Seven patients, three females (43%), and four males (57%), accounted for 33 ceftaroline samples for therapeutic drug management. A median of four samples for therapeutic drug management was collected per patient (range, 2-9 samples). The median age was 7 years (range, 1-13 yr) with a median weight of 25.5kg (range, 12.6-40.1kg). Six of seven patients (86%) demonstrated an increase in volume of distribution, five of seven patients (71%) demonstrated an increase in clearance, and 100% of patients demonstrated a shorter half-life estimate as compared with the package insert estimate. Six of seven patients (85.7%) had documented methicillin-resistant S. aureus growth from a normally sterile site with five of six (83.3%) having documented BSI, allowing six total patients to be evaluated for the secondary objective of microbiological and clinical response. All six patients achieved a positive microbiological and clinical response for a response rate of 100%. Conclusions: These data suggest the pharmacokinetics of ceftaroline in PICU patients is different than healthy pediatric and adult patients, most notably a faster clearance and larger volume of distribution. A higher mg/kg dose and a more frequent dosing interval for ceftaroline may be needed in PICU patients to provide appropriate pharmacodynamic exposures. Larger pharmacokinetic, pharmacodynamic, and interventional treatment trials in the PICU population are warranted.