Ceftaroline fosamil(cas 400827-46-5), also known as TAK 599 and PPI 0903, is an advanced-generation cephalosporin antibiotic. It is active against methicillin-resistant Staphylococcus aureus (MRSA) and Gram-positive bacteria. It retains the activity of later-generation cephalosporins having broad-spectrum activity against Gram-negative bacteria. It is currently being investigated for community-acquired pneumonia and complicated skin and skin structure infection.
1. Drugs. 2016 Nov;76(17):1659-1674.
Ceftaroline Fosamil: A Review in Complicated Skin and Soft Tissue Infections and
(1)Springer, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.
Intravenous ceftaroline fosamil (Zinforo™), a prodrug that is rapidly converted
to its active metabolite ceftaroline, is approved for use in adults and children
(from 2 months of age) with complicated skin and soft tissue infections (cSSTIs)
or community-acquired pneumonia (CAP). In several multinational trials,
ceftaroline fosamil was an effective and generally well tolerated treatment in
adult and paediatric patients with cSSTIs or CAP. In the phase 3 CANVAS trials,
ceftaroline fosamil treatment was noninferior to vancomycin plus aztreonam in
adults with cSSTIs. Based on a meta-analysis of three similarly designed, phase 3
trials (FOCUS 1, FOCUS 2 and an Asian trial), ceftaroline fosamil treatment was
superior to ceftriaxone in adults with CAP of Pneumonia Outcomes Research Teams
(PORT) risk class III or IV. Ceftaroline fosamil was also associated with high
clinical cure rates in hospitalized children (aged 2 months to 17 years) with
cSSTIs or CAP. With its broad spectrum of in vitro activity against clinically
relevant Gram-positive [including methicillin-resistant Staphylococcus aureus
(MRSA) and drug-resistant Streptococcus pneumoniae isolates] and Gram-negative
pathogens implicated in cSSTIs and CAP, ceftaroline fosamil is an important
treatment option for cSSTI and CAP in adults and children from the age of
2. Expert Rev Anti Infect Ther. 2012 Oct;10(10):1087-103. doi: 10.1586/eri.12.112.
Epub 2012 Nov 21.
Ceftaroline fosamil: a new cephalosporin active against resistant Gram-positive
organisms including MRSA.
Garrison MW(1), Kawamura NM, Wen MM.
(1)Washington State University College of Pharmacy, Spokane, WA 99210-1495, USA.
The growing prevalence of resistant Gram-positive pathogens such as
methicillin-resistant Staphylococcus aureus continues to pose a dilemma to
clinicians. With strains developing reduced susceptibility to vancomycin,
effective and well-tolerated antibiotics to combat these resistant pathogens are
needed. Ceftaroline is a new parenteral cephalosporin that has been available in
the USA for almost 2 years. Similar to other cephalosporins, it is well tolerated
with mostly mild adverse events; however, compared with existing parenteral
cephalosporins, ceftaroline has the unique attribute of being bactericidal
against resistant Gram-positive aerobes including both hospital- and
community-acquired methicillin-resistant S. aureus, S. aureus strains with
reduced susceptibility or complete resistance to vancomycin, and resistant
Streptococcus pneumoniae including multidrug-resistant strains. Current
indications in the USA and Europe include treatment of adults with complicated
skin, skin-structure infections and community-acquired pneumonia. This paper will
review the properties of ceftaroline, its spectrum of activity, clinical use,
safety profile and future role.
3. J Antimicrob Chemother. 2011 Apr;66 Suppl 3:iii45-51. doi: 10.1093/jac/dkr098.
Review of ceftaroline fosamil microbiology: integrated FOCUS studies.
Critchley IA(1), Eckburg PB, Jandourek A, Biek D, Friedland HD, Thye DA.
(1)Cerexa, Inc., Oakland, CA 94612, USA. firstname.lastname@example.org
Ceftaroline fosamil, the prodrug form of ceftaroline, is a novel broad-spectrum
parenteral cephalosporin that exhibits antibacterial activity against typical
respiratory pathogens such as Streptococcus pneumoniae, Haemophilus influenzae,
Staphylococcus aureus and common Gram-negative pathogens. In particular,
ceftaroline has activity against resistant Gram-positive cocci, including
penicillin- and multidrug-resistant S. pneumoniae, as well as
methicillin-resistant S. aureus. The activity of ceftaroline against these
phenotypes is attributed to its ability to bind to modified penicillin-binding
proteins with high affinity when compared with other β-lactams. The activity of
ceftaroline is not compromised by the ability of H. influenzae to produce
β-lactamase. Ceftaroline fosamil was compared with ceftriaxone for safety and
efficacy in two randomized, double-blinded, controlled Phase III clinical trials
for the treatment of community-acquired pneumonia (CAP). Microbiological
assessments at baseline included respiratory specimen cultures, blood cultures,
urinary antigen testing and atypical pathogen serology testing. By-subject and
by-pathogen microbiological outcomes were assessed in the microbiologically
evaluable population at the test-of-cure visit. The favourable microbiological
response rates by subject for ceftaroline were 87.0% compared with 81.0% for
ceftriaxone. The by-pathogen microbiological response rates of ceftaroline and
ceftriaxone were 87.3% and 72.9% for S. pneumoniae, 83.3% and 85.0% for H.
influenzae and 76.0% and 70.4% for S. aureus, respectively. Key baseline
pathogens such as S. pneumoniae, H. influenzae and methicillin-susceptible S.
aureus were susceptible to ceftaroline, with MIC(90)s of 0.03, 0.03 and 0.25
mg/L, respectively, supporting its utility as a promising new agent for treatment
4. J Antimicrob Chemother. 2010 Nov;65 Suppl 4:iv9-16. doi: 10.1093/jac/dkq251.
Ceftaroline fosamil: a novel broad-spectrum cephalosporin with expanded
Biek D(1), Critchley IA, Riccobene TA, Thye DA.
(1)Cerexa, Inc., Oakland, CA 94612, USA. email@example.com
Ceftaroline fosamil is a novel cephalosporin with broad-spectrum activity against
Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus
(MRSA) and multidrug-resistant Streptococcus pneumoniae, and common Gram-negative
organisms. The activity of ceftaroline against MRSA is attributed to its ability
to bind to penicillin-binding protein (PBP) 2a with high affinity and inhibit the
biochemical activity of PBP 2a more efficiently than other presently available
β-lactams. The activity of ceftaroline against MRSA and the β-haemolytic
streptococci makes it an attractive monotherapy agent for the treatment of
complicated skin and skin structure infections (cSSSIs). Recent profiling and
surveillance studies have shown that ceftaroline is active against contemporary
skin pathogens collected from US and European medical centres in 2008. The mean
free drug %T > MIC (percentage of time the drug concentration remains above the
MIC) needed for stasis ranged from 26% for S. aureus to 39% for S. pneumoniae in
the murine thigh infection model. Pharmacokinetic and pharmacodynamic target
attainment predictions for 600 mg of ceftaroline fosamil every 12 h showed that
the mean %T > MICs for which plasma free-drug concentrations exceeded an MIC of
1 and 2 mg/L were 71% and 51% of the dosing interval, respectively. For a 40% T
> MIC target, the predicted attainments for infections due to pathogens for
which ceftaroline MICs were 1 or 2 mg/L were 100% and 90%, respectively. Clinical
and microbiological successes of ceftaroline fosamil in treating cSSSIs were
demonstrated in two Phase III clinical studies, in which 96.8% of all baseline
cSSSI isolates from the microbiologically evaluable population were inhibited by
ceftaroline at ≤ 2 mg/L. Ceftaroline fosamil is a promising broad-spectrum agent
for the treatment of cSSSIs.