title: Missense mutations of PBP2a are associated with reduced susceptibility to ceftaroline and ceftobiprole in African MRSA.
abstract: OBJECTIVE
  Ceftaroline and ceftobiprole are new cephalosporins, which are active against MRSA by inhibiting PBP2a. Recently, high rates of resistance to ceftaroline were reported from Ghana. The objective of this study was to assess rates of resistance to ceftaroline and ceftobiprole in MRSA from Africa and to describe potential missense mutations of PBP2a.
  
  
  METHODS
  MRSA isolates derived from Staphylococcus aureus colonization (n = 37) and infection (n = 23) and were collected in Côte d'Ivoire (n = 17), DR Congo (n = 6), Gabon (n = 21) and Nigeria (n = 16). The MICs were determined by the broth microdilution method. The mecA gene was sequenced and missense mutations were associated with the corresponding MLST ST.
  
  
  RESULTS
  In total, 16.7% (n = 10) and 15% (n = 9) of isolates were resistant to ceftaroline and ceftobiprole, respectively. The corresponding MICs of ceftaroline and ceftobiprole correlated significantly (r = 0.92). Isolates belonging to ST241 harboured a triple mutation of PBP2a (N146K-N204K-G246E), which was associated with high rates of resistance to ceftaroline (90.9%) and ceftobiprole (81.8%).
  
  
  CONCLUSIONS
  Resistances to ceftaroline and ceftobiprole were only detected in Nigeria and were associated with ST241 and a triple mutation of PBP2a.
authors.affiliation: Institute of Medical Microbiology, University Hospital Münster, Münster, Germany frieder.schaumburg@ukmuenster.de.
authors.forename: Frieder
authors.initials: F
authors.lastname: Schaumburg
authors.affiliation: Institute of Medical Microbiology, University Hospital Münster, Münster, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Peters
authors.affiliation: Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon.
authors.forename: Abraham
authors.initials: A
authors.lastname: Alabi
authors.affiliation: Institute of Medical Microbiology, University Hospital Münster, Münster, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Becker
authors.affiliation: Institute of Medical Microbiology, University Hospital Münster, Münster, Germany.
authors.forename: Evgeny A
authors.initials: EA
authors.lastname: Idelevich
mesh_terms: D000349:Africa; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D002353:Carrier State / Q000382:microbiology; D002511:Cephalosporins / Q000494:pharmacology*; D005838:Genotype; D055624:Methicillin-Resistant Staphylococcus aureus / Q000145:classification / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D058885:Multilocus Sequence Typing; D020125:Mutation, Missense; D046915:Penicillin-Binding Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013203:Staphylococcal Infections / Q000382:microbiology; D018440:beta-Lactam Resistance; D000097583:Ceftaroline
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002511:Cephalosporins; D046915:Penicillin-Binding Proteins; D000097583:Ceftaroline; C487789:mecA protein, Staphylococcus aureus; C443755:ceftobiprole