Ceftaroline pharmacokinetics and pharmacodynamics in patients with cystic fibrosis

• Published in: Journal of cystic fibrosis 2018-05, Vol.17 (3), p.e25-e31
• Main Authors: Barsky, Emily E., Pereira, Luis M., Sullivan, Keri J., Wong, Alanna, McAdam, Alexander J., Sawicki, Gregory S., Priebe, Gregory P., Goobie, Susan M.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacokinetics; Ceftaroline; Cephalosporins - administration & dosage; Cephalosporins - pharmacokinetics; Child; Chromatography, Liquid - methods; Cystic fibrosis; Cystic Fibrosis - diagnosis; Cystic Fibrosis - drug therapy; Cystic Fibrosis - microbiology; Dose-Response Relationship, Drug; Drug Monitoring - methods; Female; Half-Life; Humans; Infection; Male; Mass Spectrometry - methods; Methicillin-Resistant Staphylococcus aureus - drug effects; Methicillin-Resistant Staphylococcus aureus - isolation & purification; Microbial Sensitivity Tests - methods; MRSA; Pharmacodynamics; Pharmacokinetics; Prospective Studies; Treatment Outcome
• ISSN: 1569-1993; 1873-5010
• DOI: 10.1016/j.jcf.2017.10.010

Methicillin-resistant Staphylococcus aureus (MRSA) is a prevalent pathogen in patients with cystic fibrosis (CF) associated with increased morbidity. Ceftaroline fosamil is an intravenous (IV) cephalosporin with activity against MRSA. There are minimal data regarding dosing in the CF population. The objective of this study was to determine the pharmacokinetic and pharmacodynamic profile of IV ceftaroline in patients with CF. We conducted a single-center prospective study of children and young adults with CF receiving ceftaroline (15mg/kg IV up to 600mg every 8h) as part of treatment for a CF pulmonary exacerbation between June 2016 and April 2017. Seven patients were enrolled for a total of 10 treatment courses. For each treatment course, up to 8 plasma samples were assayed for ceftaroline using ultra-high performance liquid chromatography with mass spectrometry. Maximum plasma concentration, systemic clearance, and elimination half-life were calculated. The area under the curve (AUC) above the minimum inhibitory concentration (MIC) and the percent time above the MIC (%fT>MIC) were determined for each subject using MICs of 0.5, 1, and 2μg/mL and the measured MIC if available. The mean (SD) age for the 7 patients was 20.3 (8.0) years. Mean (SD) maximum plasma concentration of ceftaroline was 22.7 (9.6) μg/mL, systemic clearance 7.9 (3.3) L/h, and half-life 1.1 (0.4) hours. Using a MIC of 1 μg/mL, accepted as the MIC 90 of MRSA isolates, AUC above MIC mean (SD) was 53.6 (19.5) μg·h/mL, mean (SD) %fT>MIC was 75.7 (10.4), and all subjects had >60%fT>MIC. In this cohort of CF patients, mean ceftaroline half-life was 1.1h, which is notably lower than the general population. The dosing regimen studied, which exceeds the recommended dosing in the non-CF population, was adequate to achieve >60% time above the MIC in all patients.