Plasma and Lung Tissue Pharmacokinetics of Ceftaroline Fosamil in Patients Undergoing Cardiac Surgery with Cardiopulmonary Bypass: An <em>in-vivo</em> Microdialysis Study

Antimicrob Agents Chemother. 2021 Jul 19:AAC0067921. doi: 10.1128/AAC.00679-21. Online ahead of print.

ABSTRACT

BACKGROUND: Ceftaroline fosamil, a 5th generation cephalosporin antibiotic with activity against MRSA, is currently approved for the treatment of pneumonia and complicated skin and soft tissue infections. However, pharmacokinetic data on free lung tissue concentrations in critical patient populations are lacking.

OBJECTIVES: The aim of this study was to evaluate the pharmacokinetics of the high-dose regimen of ceftaroline in plasma and lung tissue in cardiac surgery patients during intermittent and continuous administration.

MATERIALS AND METHODS: 9 patients undergoing elective cardiac surgery on cardiopulmonary bypass were included in this study and randomly assigned to intermittent or continuous administration. 1800mg ceftaroline fosamil were administered intravenously as either 600mg over 2h q8h (intermittent group) or 600mg over 2h (loading dose) and 1200mg over 22h (continuous group). Interstitial lung tissue concentrations were measured by in-vivo microdialysis. Relevant pharmacokinetic parameters were calculated for each group.

RESULTS: Plasma exposure during intermittent and continuous administration were comparable to previously published studies and did not differ significantly between both groups. In-vivo microdialysis demonstrated reliable and adequate penetration of ceftaroline into lung tissue during intermittent and continuous administration. The AUCSS 0-8 and AUCtissue/plasma ratio were descriptively higher in the continuous group. Continuous administration of ceftaroline fosamil achieved significantly higher fT4x>MIC than intermittent administration for pathogens with a minimal inhibitory concentration of 1mg/L.

CONCLUSION: Ceftaroline showed adequate penetration into interstitial lung tissue of critically ill patients undergoing major cardiothoracic surgery, supporting its use for pneumonia caused by susceptible pathogens.

PMID:34280013 | DOI:10.1128/AAC.00679-21