Affiliation:
1. Johnson & Johnson Pharmaceutical Research and Development, LLC, 1000 Route 202 South, Raritan, New Jersey 08869
Abstract
ABSTRACT
Single-step
Pseudomonas 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 the
mexXY
efflux genes. Mutants selected with ceftobiprole did not overexpress AmpC; 90% of these produced elevated levels of
mexXY
RNA, indicating that increased efflux, not AmpC derepression, is the predominant response to ceftobiprole during first-step mutations in
P. aeruginosa
.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
22 articles.
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