Ceftaroline Fosamil (DB06590): A Comprehensive Clinical and Pharmacological Monograph

Executive Summary

Ceftaroline fosamil is a fifth-generation, parenteral cephalosporin antibiotic distinguished by its unique bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA).[1][ As a water-soluble prodrug, it is rapidly converted]

in vivo to its active metabolite, ceftaroline. The drug's mechanism of action involves the inhibition of bacterial cell wall synthesis through binding to penicillin-binding proteins (PBPs), with a uniquely high affinity for PBP2a, the protein responsible for methicillin resistance in staphylococci.[2]

The United States Food and Drug Administration (FDA) has approved ceftaroline fosamil for two primary indications: the treatment of acute bacterial skin and skin structure infections (ABSSSI), including those caused by MRSA, and community-acquired bacterial pneumonia (CABP).[5] Its efficacy was established in four pivotal Phase III clinical trials. The CANVAS 1 and 2 trials demonstrated non-inferiority to a combination of vancomycin and aztreonam for ABSSSI, with high clinical cure rates against both MSSA and MRSA.[7][ The FOCUS 1 and 2 trials established non-inferiority to ceftriaxone for CABP and showed numerically superior cure rates, particularly in patients with infections caused by]

Streptococcus pneumoniae.[7]

The safety profile of ceftaroline fosamil is generally well-tolerated and consistent with the cephalosporin class. The most common adverse reactions include diarrhea, nausea, and rash.[1][ Key warnings and precautions include the potential for hypersensitivity reactions,]