Ceftaroline: a Cephalosporin with Anti-MRSA Activity

Abstract

Ceftaroline is a cephalosporin antibiotic with broad-spectrum activity against gram-positive and gram-negative bacteria, including contemporary resistant gram-positive phenotypes, such as methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Streptococcus pneumoniae, and penicillin-resistant S. pneumoniae. Ceftaroline is administered as the prodrug ceftaroline fosamil, which is rapidly converted via plasma phosphatases to its bioactive metabolite, ceftaroline. Ceftaroline fosamil was approved in October 2010 by the U.S. Food and Drug Administration (FDA) and launched in March 2011 for the treatment of acute bacterial skin and skin structure infections and for the treatment of community-acquired bacterial pneumonia caused by designated susceptible isolates. The Clinical and Laboratory Standards Institute (CLSI) designated ceftaroline a member of a new subclass of β-lactam antimicrobials, cephalosporins with anti-MRSA activity, based on its unique spectrum of activity. At this time, no ceftaroline surrogate is recommended for in vitro susceptibility testing because no other FDA-approved β-lactam has a similar spectrum of activity, although studies to identify potential surrogates are in progress. Ceftaroline susceptibility testing can be performed using CLSI standardized dilution or diffusion techniques, and FDA susceptibility interpretive criteria for broth dilution MIC values and disk diffusion zone diameters are available. Commercial broth-based antimicrobial susceptibility tests for ceftaroline are in development. A ceftaroline Etest for MIC testing is also in development. Ceftaroline Kirby-Bauer disks for diffusion were recently approved by the FDA and have been validated against the reference broth microdilution method.