title: Activity of ceftobiprole against methicillin-resistant Staphylococcus aureus strains with reduced susceptibility to daptomycin, linezolid or vancomycin, and strains with defined SCCmec types.
abstract: Ceftobiprole is a broad-spectrum cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative pathogens including Pseudomonas aeruginosa. The aim of this study was to evaluate the activity of ceftobiprole against MRSA isolates with decreased susceptibility to daptomycin, linezolid or vancomycin as well as isolates from staphylococcal chromosome cassette mec (SCCmec) types I, II, III and IV. Overall, ceftobiprole demonstrated high potency against the 216 isolates tested, with MIC50 and MIC90 values (minimum inhibitory concentrations required to inhibit 50% and 90% of the isolates, respectively) of 1mg/L and 2mg/L (97.2% susceptible). The MIC90 for ceftobiprole was 2mg/L against the linezolid-non-susceptible, daptomycin-non-susceptible and vancomycin-intermediate (VISA and hVISA) subsets and was 1mg/L against the vancomycin-resistant (VRSA) strains. The MIC50/90 values for ceftobiprole were 2/4, 1/2, 2/2 and 1/1mg/L against SCCmec types I, II, III and IV, respectively. SCCmec type I strains had the highest MICs, with six strains exhibiting a ceftobiprole MIC of 4mg/L and 15 strains at 2mg/L. Ceftobiprole demonstrated potent activity against MRSA, including subsets of isolates with reduced susceptibility to daptomycin, linezolid and vancomycin. The activity of ceftobiprole against these resistant phenotypes indicates that it may have clinical utility in the treatment of infections caused by multidrug-resistant S. aureus and across strains from prevalent SCCmec types.
authors.affiliation: JMI Laboratories, North Liberty, IA 52317, USA; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. Electronic address: david-farrell@jmilabs.com.
authors.forename: David J
authors.initials: DJ
authors.lastname: Farrell
authors.affiliation: JMI Laboratories, North Liberty, IA 52317, USA.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Flamm
authors.affiliation: JMI Laboratories, North Liberty, IA 52317, USA; Division of Infectious Diseases, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Helio S
authors.initials: HS
authors.lastname: Sader
authors.affiliation: JMI Laboratories, North Liberty, IA 52317, USA; Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002511:Cephalosporins / Q000494:pharmacology*; D017576:Daptomycin / Q000494:pharmacology*; D000069349:Linezolid; D055624:Methicillin-Resistant Staphylococcus aureus / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D008826:Microbial Sensitivity Tests; D023303:Oxazolidinones / Q000494:pharmacology*; D013203:Staphylococcal Infections / Q000188:drug therapy; D014640:Vancomycin / Q000494:pharmacology*
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D023303:Oxazolidinones; C443755:ceftobiprole; D014640:Vancomycin; D000069349:Linezolid; D017576:Daptomycin
keywords: Antimicrobial resistance; Ceftobiprole; MRSA