Ceftaroline: A Novel Broad-Spectrum Cephalosporin with Activity against Meticillin-Resistant Staphylococcus aureus

• Published in: Drugs (New York, N.Y.) N.Y.), 2009-01, Vol.69 (7), p.809-831
• Main Authors: Zhanel, George G., Sniezek, Grace, Schweizer, Frank, Zelenitsky, Sheryl, Lagacé-Wiens, Philippe R. S., Rubinstein, Ethan, Gin, Alfred S., Hoban, Daryl J., Karlowsky, James A.
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacterial diseases; Biological and medical sciences; Ceftaroline; Cephaloridine; Cephalosporins; Cephalosporins - adverse effects; Cephalosporins - pharmacology; Cephalosporins - therapeutic use; Clinical Trials as Topic; Dosage and administration; Drug Interactions; Drug Resistance, Bacterial; Drug therapy; Human bacterial diseases; Humans; Infectious diseases; Internal Medicine; Medical sciences; Medicine; Medicine & Public Health; Methicillin-Resistant Staphylococcus aureus - drug effects; Moxalactam; Pathogens; Patient outcomes; Penicillin; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacotherapy; Pneumonia; Review Article; Staphylococcal Infections - drug therapy; Staphylococcal infections, streptococcal infections, pneumococcal infections; Staphylococcus aureus infections; Staphylococcus infections; Streptococcus infections; Surveillance
• ISSN: 0012-6667; 1179-1950
• DOI: 10.2165/00003495-200969070-00003

Ceftaroline is a broad-spectrum cephalosporin currently under clinical investigation for the treatment of complicated skin and skin-structure infections (cSSSI), including those caused by meticillin-resistant Staphylococcus aureus (MRSA), and community-acquired pneumonia (CAP). 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 antibacterials. The high binding affinity of ceftaroline to PBP2a (median inhibitory concentration 0.90 μg/mL) correlates well with its low minimum inhibitory concentration for MRSA. Ceftaroline is active in vitro against Gram-positive cocci, including MRSA, meticillin-resistant Staphylococcus epidermidis , penicillin-resistant Streptococcus pneumoniae and vancomycin-resistant Enterococcus faecalis (not E. faecium). The broad-spectrum activity of ceftaroline includes many Gram-negative pathogens but does not extend to extended-spectrum β-lactamase-producing or AmpC-derepressed Enterobacteriaceae or most nonfermentative Gram-negative bacilli. Ceftaroline demonstrates limited activity against anaerobes such as Bacteroides fragilis and non-fragilis Bacteroides spp. Limited data show that ceftaroline has a low propensity to select for resistant subpopulations. Ceftaroline fosamil (prodrug) is rapidly converted by plasma phosphatases to active ceftaroline. For multiple intravenous doses of 600 mg given over 1 h every 12 hours for 14 days, the maximum plasma concentration was 19.0 μg/mL and 21.0 μg/mL for first and last dose, respectively. Ceftaroline has a volume of distribution of 0.37 L/kg (28.3 L), low protein binding (