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Clinical Medicine Reviews in Therapeutics

Ceftaroline Fosamil—A New Broad-Spectrum Cephalosporin with Significant Activity against Methicillin-Resistant Staphylococci

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Clinical Medicine Reviews in Therapeutics 2011:3

Review

Published on 27 Feb 2011

DOI: 10.4137/CMRT.S6650


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Abstract

Ceftaroline fosamil (PPI-0903, TAK-599, Teflaro®, Forest Pharmaceuticals) is the prodrug for ceftaroline (T-91825), a broad-spectrum parenteral (IM/IV) cephalosporin with potent in vitro and in vivo activity against methicillin- and vancomycin-resistant staphylococci as well as other common pathogens of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CAP). Although more active than other cephalosporins against enterococci, the potency of this agent is still modest against E. faecalis (inactive vs. E. faecium). It is also active against Enterobacteriaceae with the exceptions of strains producing extended-spectrum beta-lactamases or carbapenemases. It is also active against anaerobic organisms with the exceptions of Bacteroides and Prevotella species and Clostridium difficile. Ceftaroline fosamil is non-inferior compared with regimens of vancomycin with/without aztreonam (ABSSSI) and ceftriaxone (CAP). The usual dosage regimen is 600 mg every 12 hours, as a 1-hour IV infusion, with dosage adjustment in moderate renal impairment (creatinine clearance [CrCl] of 31–50 mL/min) to 400 mg every 12 hours, in severe renal impairment (CrCl 15–30 mL/min) to 300 mg every 12 hours, and in end-stage renal impairment/hemodialysis (CrCl < 15 mL/min) to 200 mg every 12 hours. Further studies continue with a combination product of ceftaroline fosamil with NXL104 (a beta-lactamase inhibitor).

This paper will review the chemistry, mechanism of action, in vitro and in vivo (animal) antibacterial activity, pharmacokinetics, clinical efficacy, tolerability, dosing and administration, and role of this agent. Medline/PubMed, International Pharmaceutical Abstracts, and EMBASE databases were searched for relevant articles using the search terms “ceftaroline”, “PPI-0903”, “TAK-599”, and “T-91825”. All English and French language articles identified in the searches were reviewed for their relevance to this review. In addition, the bibliographies of retrieved articles were reviewed to identify any relevant articles not identified in the initial searches. Also, the proceedings of all Interscience Conferences on Antimicrobial Agents and Chemotherapy (American Society for Microbiology) from 2000 through 2010 were searched for relevant abstracts.



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