title: Review of ceftaroline fosamil microbiology: integrated FOCUS studies.
abstract: 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 of CAP.
authors.affiliation: Cerexa, Inc., Oakland, CA 94612, USA. icritchley@cerexa.com
authors.forename: Ian A
authors.initials: IA
authors.lastname: Critchley
authors.forename: Paul B
authors.initials: PB
authors.lastname: Eckburg
authors.forename: Alena
authors.initials: A
authors.lastname: Jandourek
authors.forename: Donald
authors.initials: D
authors.lastname: Biek
authors.forename: H David
authors.initials: HD
authors.lastname: Friedland
authors.forename: Dirk A
authors.initials: DA
authors.lastname: Thye
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology*; D002443:Ceftriaxone / Q000008:administration & dosage / Q000494:pharmacology; D002511:Cephalosporins / Q000008:administration & dosage* / Q000494:pharmacology; D017714:Community-Acquired Infections / Q000188:drug therapy* / Q000382:microbiology*; D004311:Double-Blind Method; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000302:isolation & purification; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D008826:Microbial Sensitivity Tests; D016896:Treatment Outcome; D000097583:Ceftaroline
chemical_list: D000900:Anti-Bacterial Agents; D002443:Ceftriaxone; D002511:Cephalosporins; D000097583:Ceftaroline