Ceftaroline fosamil: a new broad-spectrum cephalosporin

Ceftaroline fosamil: a new broad-spectrum cephalosporin

Joseph B. Laudano*

Medical Affairs, Forest Research Institute, Harborside Financial Center, Plaza V, Jersey City, NJ 07311, USA

*Tel: +1-201-427-8409; Fax: +1-201-427-8200; E-mail: joseph.laudano@frx.com

Ceftaroline fosamil, the prodrug of the active metabolite, ceftaroline, is a new, broad-spectrum cephalosporin

recently approved in the USA for the treatment of acute bacterial skin and skin structure infections (ABSSSIs)

and community-acquired bacterial pneumonia (CABP). Ceftaroline has potent in vitro activity against Grampositive

organisms, including methicillin-resistant Staphylococcus aureus and Streptococcus pneumoniae, as

well as common Gram-negative organisms. The high affinity of ceftaroline for penicillin-binding proteins is

responsible for the potent activity observed against clinically relevant pathogens. With respect to the treatment

of CABP, the activity of ceftaroline against pathogens such as S. pneumoniae, S. aureus, Haemophilus influenzae

and Moraxella catarrhalis demonstrates coverage across a broad range of pathogens typically encountered in

clinical practice. Ceftaroline is also very active against common pathogens seen in ABSSSIs such as S. aureus

(methicillin-susceptible S. aureus and methicillin-resistant S. aureus) and Streptococcus pyogenes. Ceftaroline

exhibits a dose-proportional pharmacokinetic profile, similar to other renally excreted cephalosporins, and

has a well-tolerated safety profile consistent with the cephalosporin class. Ceftaroline fosamil is compatible

via Y-site administration with many other commonly administered parenteral drugs.

Keywords: CAP, community-acquired pneumonia, CABP, MRSA, Streptococcus pneumoniae

Introduction

The cephalosporin class of antimicrobial agents is known for its

broad spectrum of activity, proven efficacy and favourable

safety profile, making it the most commonly prescribed class

of antimicrobials (data on file, Forest Laboratories, Inc. and references

herein1–5). There are four recognized class generations of

cephalosporins based on spectra of activity.6 First-generation

cephalosporins are active against Gram-positive cocci; secondgeneration

agents retain this Gram-positive activity and have

increased activity against Gram-negative organisms. Thirdgeneration

cephalosporins have decreased activity against

Gram-positive organisms relative to first- and second-generation

agents, but improved Gram-negative coverage. Spectrum of

activity is further expanded in the fourth-generation agents,

which have increased activity against Gram-negative organisms

compared with first- and second-generation agents and

greater coverage of Gram-positive organisms than thirdgeneration

agents, as well as activity against Pseudomonas

spp. and some Enterobacteriaceae, including those that

produce b-lactamases. Ceftaroline fosamil (TAK-599 or

PPI-0903), the prodrug of the active metabolite, ceftaroline,

was synthesized by Takeda Pharmaceutical Co., Ltd and developed

by Cerexa, Inc. and Forest Laboratories, Inc.7 The CLSI designates

ceftaroline as a member of a new subclass of

antimicrobials, cephalosporins with anti-methicillin-resistant Staphylococcus

aureus (MRSA) activity.8 Ceftaroline has also been

described in the literature as a ‘fifth-generation’

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