ppi-0903 and Critical-Illness

Topics: Acute Kidney Injury; Adult; Ceftaroline; Cephalosporins; Continuous Renal Replacement Therapy; Critical Illness; Humans

Topics: Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Critical Illness; Humans; Meningitis, Pneumococcal

Currently, no dosing information exists for ceftaroline fosamil in patients undergoing continuous renal replacement therapy (CRRT). The objectives of this study are to characterize the pharmacokinetics of ceftaroline in critically ill patients undergoing CRRT modalities and to derive individualized dosing recommendations.. This pharmacokinetic study aimed to enroll critically ill patients receiving ceftaroline fosamil and any CRRT modality from adult intensive care units. Selection of the specific CRRT modality and dosing regimen was based on clinical discretion. Pre-filter, post-filter, and ultrafiltrate samples were obtained before the administration of the fourth dose, after the completion of the infusion, and up to five additional time points post-infusion. Plasma concentrations were measured using a validated ultra-high performance liquid chromatography assay. Individual pharmacokinetic parameters were calculated using non-compartmental analysis.. Ceftaroline is cleared extensively in critically ill patients receiving CRRT and may impact pharmacodynamic target achievement. Dose adjustments should be based on the intensity of the CRRT regimen, patient weight, and the clinical status of the patient.

Topics: Adult; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Continuous Renal Replacement Therapy; Critical Illness; Dose-Response Relationship, Drug; Humans; Intensive Care Units

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.. Retrospective electronic medical record review.. Free-standing tertiary/quaternary pediatric children's hospital.. Critically ill children receiving ceftaroline monotherapy or combination therapy for suspected or confirmed methicillin-resistant S. aureus infections in the PICU.. None.. 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 25.5 kg (range, 12.6-40.1 kg). 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%.. 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.

Topics: Adolescent; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Child; Child, Preschool; Critical Illness; Female; Humans; Infant; Intensive Care Units, Pediatric; Male; Methicillin-Resistant Staphylococcus aureus; Prospective Studies; Retrospective Studies; Staphylococcal Infections; Treatment Outcome