antibioticsbooks

Fifth-Generation
Cephalosporins
Agents: ceftaroline
One new cephalosporin is available that has unique
characteristics. We are anticipating that it will
be marketed as “fifth-generation” cephalosporin,
although there is no consensus on the issue yet.
What makes this agent unique is activity against
MRSA. Its structure has been engineered to bind
to the penicillin-binding protein 2a of MRSA that
has low affinity for other beta-lactams. Unlike other
cephalosporins, ceftaroline also has modest activity
against Enterococcus faecalis (but not Enterococcus
faecium). It lost some of the Gram-negative potency
of cefepime and has Gram-negative activity closer to
that of ceftriaxone. In an era of high MRSA prevalence,
ceftaroline offers an intriguing possibility for
therapy, but because it is so new its role is not yet
defined. Another agent with similar characteristics
exists (ceftobiprole), but it was removed from the
market in the few countries in which it was approved
after U.S. and E.U. regulators did not approve it.
Mechanism of Action
All beta-lactams inhibit cross-linking of peptidoglycan
in the cell wall, leading to autolysis and cell
death. Unlike other beta-lactams, ceftaroline can
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