title: Avibactam reverts the ceftazidime MIC90 of European Gram-negative bacterial clinical isolates to the epidemiological cut-off value.
abstract: OBJECTIVE
  Ceftazidime-avibactam consists of the beta-lactam ceftazidime and the novel non-beta-lactam beta-lactamase inhibitor avibactam. The effect of avibactam on the ceftazidime MIC frequency distribution of Gram-negative European clinical isolates was observed and compared to European Committee for Antimicrobial Susceptibility Testing (EUCAST) MIC frequency distributions and epidemiological cut-off values (ECOFFs) listed for ceftazidime.
  
  
  METHODS
  Ceftazidime and ceftazidime-avibactam MICs were determined using Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution methods for Pseudomonas aeruginosa, Escherichia coli, Klebsiella spp., Serratia spp., Enterobacter spp., and Proteus mirabilis isolates collected from medical centres in Europe during 2009.
  
  
  RESULTS
  The MIC(90) values for ceftazidime and ceftazidime-avibactam against P. aeruginosa isolates from a 2009 European surveillance programme were >32 and 8 mg/l, respectively. That is, the presence of avibactam reverted the ceftazidime MIC(90) for P. aeruginosa to the ECOFF. Similarly, the MIC(90) values for ceftazidime against E. coli, Klebsiella spp., Serratia spp., and P. mirabilis were also reduced to the ECOFF by the presence of avibactam. Avibactam reduced the ceftazidime MIC(90) value against collected Enterobacter spp. to 1 mg/l (>32-fold reduction). No ECOFF has been defined for Enterobacter spp. however, it is 1 mg/l for Enterobacter aerogenes and Enterobacter cloacae.
  
  
  CONCLUSIONS
  The presence of avibactam reverted the ceftazidime MIC(90) for Gram-negative bacteria to the ECOFF.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Flamm
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Stone
authors.forename: Helio S
authors.initials: HS
authors.lastname: Sader
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
authors.forename: Wright W
authors.initials: WW
authors.lastname: Nichols
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D053961:Azabicyclo Compounds / Q000494:pharmacology*; D002442:Ceftazidime / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008826:Microbial Sensitivity Tests
chemical_list: D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; C543519:avibactam; D002442:Ceftazidime
keywords: Ceftazidime-avibactam,; ECOFF,; Gram-negative bacteria