Case Reports in Infectious Diseases (Jan 2018)

In Vivo Resistance to Ceftolozane/Tazobactam in Pseudomonas aeruginosa Arising by AmpC- and Non-AmpC-Mediated Pathways

  • Erik Skoglund,
  • Henrietta Abodakpi,
  • Rafael Rios,
  • Lorena Diaz,
  • Elsa De La Cadena,
  • An Q. Dinh,
  • Javier Ardila,
  • William R. Miller,
  • Jose M. Munita,
  • Cesar A. Arias,
  • Vincent H. Tam,
  • Truc T. Tran

DOI
https://doi.org/10.1155/2018/9095203
Journal volume & issue
Vol. 2018

Abstract

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Two pairs of ceftolozane/tazobactam susceptible/resistant P. aeruginosa were isolated from 2 patients after exposure to β-lactams. The genetic basis of ceftolozane/tazobactam resistance was evaluated, and β-lactam-resistant mechanisms were assessed by phenotypic assays. Whole genome sequencing identified mutations in AmpC including the mutation (V213A) and a deletion of 7 amino acids (P210–G216) in the Ω-loop. Phenotypic assays showed that ceftolozane/tazobactam resistance in the strain with AmpCV213A variant was associated with increased β-lactamase hydrolysis activity. On the other hand, the deletion of 7 amino acids in the Ω-loop of AmpC did not display enhanced β-lactamase activity. Resistance to ceftolozane/tazobactam in P. aeruginosa is associated with changes in AmpC; however, the apparent loss of β-lactamase activity in AmpC∆7 suggests that non-AmpC mechanisms could play an important role in resistance to β-lactam/β-lactamase inhibitor combinations.