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Resistance to Ceftolozane/Tazobactam in Arising by AmpC- and Non-AmpC-Mediated Pathways

Overview
Journal Case Rep Infect Dis
Publisher Wiley
Specialty Infectious Diseases
Date 2019 Jan 25
PMID 30675406
Citations 18
Authors
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
Affiliations
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Abstract

Two pairs of ceftolozane/tazobactam susceptible/resistant were isolated from 2 patients after exposure to -lactams. The genetic basis of ceftolozane/tazobactam resistance was evaluated, and -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 variant was associated with increased -lactamase hydrolysis activity. On the other hand, the deletion of 7 amino acids in the Ω-loop of AmpC did not display enhanced -lactamase activity. Resistance to ceftolozane/tazobactam in is associated with changes in AmpC; however, the apparent loss of -lactamase activity in AmpC∆7 suggests that non-AmpC mechanisms could play an important role in resistance to -lactam/-lactamase inhibitor combinations.

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