Missense mutations of PBP2a are associated with reduced susceptibility to ceftaroline and ceftobiprole in African MRSA

J Antimicrob Chemother. 2016 Jan;71(1):41-4. doi: 10.1093/jac/dkv325. Epub 2015 Oct 5.

Abstract

Objectives: 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.

MeSH terms

  • Africa
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / genetics*
  • Carrier State / microbiology
  • Ceftaroline
  • Cephalosporins / pharmacology*
  • Genotype
  • Methicillin-Resistant Staphylococcus aureus / classification
  • Methicillin-Resistant Staphylococcus aureus / enzymology*
  • Methicillin-Resistant Staphylococcus aureus / genetics
  • Methicillin-Resistant Staphylococcus aureus / isolation & purification
  • Microbial Sensitivity Tests
  • Multilocus Sequence Typing
  • Mutation, Missense*
  • Penicillin-Binding Proteins / genetics*
  • Sequence Analysis, DNA
  • Staphylococcal Infections / microbiology
  • beta-Lactam Resistance*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Cephalosporins
  • Penicillin-Binding Proteins
  • mecA protein, Staphylococcus aureus
  • ceftobiprole