Open AccessDifferential Selection of Single-Step AmpC or Efflux Mutants of Pseudomonas aeruginosa by Using Cefepime, Ceftazidime, or Ceftobiprole
Author(s) -
Anne Marie Queenan,
Wenchi Shang,
Karen Bush,
Robert K. Flamm
Publication year - 2010
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.00060-10
Subject(s) - cefepime , ceftazidime , efflux , pseudomonas aeruginosa , derepression , microbiology and biotechnology , mutant , biology , chemistry , bacteria , biochemistry , gene , gene expression , genetics , psychological repression
Single-stepPseudomonas aeruginosa mutants, selected with ceftobiprole, ceftazidime, or cefepime, were generated at frequencies of 10−6 to <10−9 at two and four times the MIC. The chromosomal AmpC β-lactamase activity was increased in all ceftazidime-selected mutants. Mutants selected with cefepime either increased AmpC activity or upregulated expression of themexXY efflux genes. Mutants selected with ceftobiprole did not overexpress AmpC; 90% of these produced elevated levels ofmexXY RNA, indicating that increased efflux, not AmpC derepression, is the predominant response to ceftobiprole during first-step mutations inP. aeruginosa .