Activity of cephalosporin CXA-101 (FR264205) against Pseudomonas aeruginosa and Burkholderia cepacia group strains and isolates

Int J Antimicrob Agents. 2009 Nov;34(5):402-6. doi: 10.1016/j.ijantimicag.2009.03.021. Epub 2009 May 9.

Abstract

Twenty-five years after its introduction, ceftazidime remains the most active cephalosporin against Pseudomonas aeruginosa. Nevertheless, resistance arises by upregulation of AmpC beta-lactamase, by efflux or, less often, via acquisition of additional beta-lactamases. Mutational resistance is especially prevalent among cystic fibrosis (CF) isolates. We examined the activity of a novel oxyimino-aminothiazolyl cephalosporin, CXA-101 (FR264205), against P. aeruginosa strains with defined resistance mechanisms as well as against multiresistant clinical CF isolates of P. aeruginosa and Burkholderia cepacia. Minimum inhibitory concentrations (MICs) of CXA-101 were determined by the Clinical and Laboratory Standards Institute agar dilution method and were 0.25-0.5 mg/L for 'typical' P. aeruginosa strains without acquired resistance, compared with 1-2 mg/L for ceftazidime. MICs of CXA-101 were 0.5-2 mg/L and 4 mg/L, respectively, for isolates with upregulated efflux or total AmpC derepression, compared with 2-16 mg/L and 32-128 mg/L for ceftazidime. Full activity was retained against OprD mutants resistant to imipenem. Substantive resistance (MICs > or = 32 mg/L) arose for transconjugants with PER, VEB and OXA extended-spectrum beta-lactamases and for metallo-beta-lactamase producers, with reduced susceptibility (MIC = 8 mg/L) for transconjugants with OXA-2, OXA-3 and NPS-1 enzymes. MICs of CXA-101 were 2- to 16-fold below those of ceftazidime for multiresistant P. aeruginosa from CF patients, but ranged up to > 128 mg/L; values for B. cepacia from CF resembled those for ceftazidime.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-Bacterial Agents / pharmacology*
  • Burkholderia Infections / microbiology
  • Burkholderia cepacia / drug effects*
  • Burkholderia cepacia / isolation & purification
  • Cephalosporins / pharmacology*
  • Drug Resistance, Bacterial
  • Female
  • Humans
  • Microbial Sensitivity Tests
  • Middle Aged
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / isolation & purification
  • Young Adult

Substances

  • Anti-Bacterial Agents
  • Cephalosporins
  • ceftolozane