<i>In Vivo</i> Resistance to Ceftolozane/Tazobactam in <i>Pseudomonas aeruginosa</i> Arising by AmpC- and Non-AmpC-Mediated Pathways
Journal
Case Reports in Infectious Diseases
ISSN
2090-6625
2090-6633
Date Issued
2018
Author(s)
Erik Skoglund
Henrietta Abodakpi
Rafael Rios
Lorena Diaz
Elsa De La Cadena
An Q. Dinh
Javier Ardila
William R. Miller
Cesar A. Arias
Vincent H. Tam
Truc T. Tran
Type
Resource Types::text::journal::journal article
Abstract
<jats:p>Two pairs of ceftolozane/tazobactam susceptible/resistant <jats:italic>P. aeruginosa</jats:italic> were isolated from 2 patients after exposure to <jats:italic>β</jats:italic>-lactams. The genetic basis of ceftolozane/tazobactam resistance was evaluated, and <jats:italic>β</jats:italic>-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 AmpC<jats:sub>V213A</jats:sub> variant was associated with increased <jats:italic>β</jats:italic>-lactamase hydrolysis activity. On the other hand, the deletion of 7 amino acids in the Ω-loop of AmpC did not display enhanced <jats:italic>β</jats:italic>-lactamase activity. Resistance to ceftolozane/tazobactam in <jats:italic>P. aeruginosa</jats:italic> is associated with changes in AmpC; however, the apparent loss of <jats:italic>β</jats:italic>-lactamase activity in AmpC∆7 suggests that non-AmpC mechanisms could play an important role in resistance to <jats:italic>β</jats:italic>-lactam/<jats:italic>β</jats:italic>-lactamase inhibitor combinations.</jats:p>
Subjects
beta-lactamase
;
tazobactam
;
evolution
;
spectrum