CEFTAROLINE

CEFTAROLINE

Ceftaroline is an antibiotic which used to treat bacterial infections. This is a

cephalosporin antibiotic. It works by stopping the growth of bacteria.

Ceftaroline is a new intravenous (IV) cephalosporin that was FDA-approved

October 2010. It is labeled for the treatment of adults with infections caused by
susceptible bacteria, specifically skin and skin structure infections (SSSIs) caused
by methicillin- sensitivity.

CHEMISTRY

Ceftaroline fosamil is used in form of the acetate. It is a prodrug that is converted

to active metabolite ceftaroline and inactive metabolite ceftaroline-M1. Initial in
vitro and in vivo animal studies referred to ceftaroline fosamil acetate as PPI-0903.
HOW CEFTAROLINE WORKS?

Ceftaroline is a broad-spectrum cephalosporin. Ceftaroline has the ability to bind

to penicillin-binding protein (PBP) 2a, an MRSA-specific PBP that has low
affinity for most other β -lactam antibacterial. The high binding affinity of
ceftaroline to PBP 2a (median inhibitory concentration 0.90 μg/mL) correlates well
with its low minimum inhibitory concentration for MRSA.

MECHANISM OF ACTION
Ceftaroline was developed by modifying the structure of the fourth-generation
cephalosporin cefozopran.14 The prodrug, ceftaroline fosamil, which contains a
phosphono group to increase water solubility, is rapidly converted in plasma into
the bioactive agent, ceftaroline (Figure 1).15 The 1,3-thiazole ring attached to the
3-position of the cephalosporin nucleus and the oxime group in the C7 acyl moiety
are responsible for the enhanced anti-MRSA activity observed with ceftaroline.

DOSAGE FORM
Injection, powder for solution in vial.
DOSAGE AND ADMINISTRATION
600 mg every 12 hours by IV infusion administered over 1 hour in adults 18 years
of age.

Dosage adjustment in patients with renal impairment.

INDICATIONS
Acute Bacterial Skin and Skin Structure Infections
ceftaroline is indicated for the treatment of acute bacterial skin and skin structure
infections (ABSSSI) caused by susceptible isolates of the following Gram-positive
and Gram-negative microorganisms: Staphylococcus aureus (including methicillin-
susceptible and -resistant isolates), Streptococcus pyogenes, Streptococcus
agalactiae, Escherichia coli, Klebsiella pneumoniae, and Klebsiella oxytoca.
Community-Acquired Bacterial Pneumonia
ceftaroline is indicated for the treatment of community-acquired bacterial
pneumonia (CABP) caused by susceptible isolates of the following Gram-positive
and Gram-negative microorganisms: Streptococcus pneumoniae (including cases
with concurrent bacteremia), Staphylococcus aureus (methicillin-susceptible
isolates only), Haemophilus influenzae, Klebsiella pneumoniae, Klebsiella
oxytoca, and Escherichia coli.

PHARMACOKINETICS

Half-Life: 2.6 hr

Peak Plasma Concentration: 21.3 mcg/mL

Peak Plasma Time: 1 hr

Volume of distribution : 20.3 L

Protein Bound: 20%

Metabolism: Ceftaroline fosamil converted to bioactive ceftaroline in plasma by

phosphatase enzyme; undergoes hydrolysis

Clearance: 9.6 L/hr

STORAGE/STABILITY

Store vials refrigerated between 36° and 46°F. Reconstituted solution in infusion
bag should be used within 6 h when stored at room temperature or within 24 h
when stored under refrigeration between 36° and 46°F.

ADVERSE EFFECT

Diarrhea (5%)

Nausea (4%)

Rash (3%)

Constipation (2%)

Vomiting (2%)

Increased transaminases (2%)

Hypokalemia (2%)

Phlebitis (2%)

CONTRAINDICATION

Hypersensitivity to ceftaroline or other members of the cephalosporin class.

CEFTAROLINE PREGNANCY WARNINGS

Animal studies have failed to reveal evidence of fetal harm. There are no
controlled data in human pregnancy. FDA pregnancy category B: Animal
reproduction studies have failed to demonstrate a risk to the fetus and there are no
adequate and well-controlled studies in pregnant women.

FDA pregnancy category: B Ceftaroline should be used during pregnancy only if

the benefit outweighs the risk to the fetus.