title: Genotypic Characterization of Methicillin-Resistant Staphylococcus aureus Recovered at Baseline from Phase 3 Pneumonia Clinical Trials for Ceftobiprole.
abstract: Baseline methicillin-resistant Staphylococcus aureus (MRSA) isolates from patients with nosocomial and community-acquired pneumonia collected during Phase 3 trials for ceftobiprole were characterized. Eighty-four unique isolates from patients enrolled in Europe (50.0%), Asia-Western Pacific region (APAC; 20.2%), North America (19.0%), Latin America (8.3%), and South Africa (2.4%) were included. Antimicrobial susceptibility testing was performed by broth microdilution and isolates screened for Panton-Valentine leukocidin. SCCmec and agr types were determined. Strains were subjected to pulsed-field gel electrophoresis and spa typing. Clonal complexes (CCs) were assigned based on spa and/or multilocus sequence typing. Most isolates were CC5-MRSA-I/II/IV (44.0%; 37/84), followed by CC8-MRSA-IV (22.6%; 19/84) and CC239-MRSA-III (21.4%; 18/84). Other MRSA formed seven clonal clusters. Isolates from North America were associated with USA100, while those from South America belonged to the Cordobes/Chilean CC. A greater clonal diversity was observed in Europe; however, each country had CC5, CC8, or CC239 as prevalent lineages. Isolates from APAC were CC5-MRSA-II (47.1%; 8/17) or CC239-MRSA-III (47.1%; 8/17). Isolates carrying SCCmec I and III had ceftobiprole MIC50 values of 2 μg/ml, while those isolates with SCCmec II and IV had MIC50 values of 1 μg/ml. Ceftobiprole inhibited 96% and 100.0% of the isolates at ≤ 2 and ≤ 4 μg/ml, respectively. These isolates represented common circulating MRSA clones. Ceftobiprole demonstrated in vitro activity with a slight variation of minimum inhibitory concentrations (MICs) according to SCCmec or clonal type.
authors.affiliation: JMI Laboratories , North Liberty, Iowa.
authors.forename: Rodrigo E
authors.initials: RE
authors.lastname: Mendes
authors.affiliation: JMI Laboratories , North Liberty, Iowa.
authors.forename: Lalitagauri M
authors.initials: LM
authors.lastname: Deshpande
authors.affiliation: JMI Laboratories , North Liberty, Iowa.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Costello
authors.affiliation: JMI Laboratories , North Liberty, Iowa.
authors.forename: David J
authors.initials: DJ
authors.lastname: Farrell
authors.affiliation: JMI Laboratories , North Liberty, Iowa.
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
authors.affiliation: JMI Laboratories , North Liberty, Iowa.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Flamm
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001208:Asia; D001427:Bacterial Toxins / Q000235:genetics; D002511:Cephalosporins / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D017714:Community-Acquired Infections / Q000188:drug therapy / Q000382:microbiology; D003428:Cross Infection / Q000188:drug therapy / Q000382:microbiology; D005060:Europe; D005098:Exotoxins / Q000235:genetics; D005838:Genotype; D006801:Humans; D007956:Leukocidins / Q000235:genetics; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics*; D008826:Microbial Sensitivity Tests / Q000379:methods; D058885:Multilocus Sequence Typing / Q000379:methods; D009656:North America; D011014:Pneumonia / Q000188:drug therapy* / Q000382:microbiology; D013019:South Africa; D013020:South America; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D002511:Cephalosporins; D005098:Exotoxins; D007956:Leukocidins; C078284:Panton-Valentine leukocidin; C443755:ceftobiprole