Affiliation:
1. Servicio de Microbiología and Unidad de Investigación, Hospital Universitario Son Espases, Instituto de Investigación Sanitaria de las Islas Baleares (IdISBa), Palma de Mallorca, Spain
Abstract
ABSTRACT
Inhaled administration of high doses of aminoglycosides is a key maintenance treatment of
Pseudomonas aeruginosa
chronic respiratory infections in cystic fibrosis (CF). We analyzed the dynamics and mechanisms of stepwise high-level tobramycin resistance development
in vitro
and compared the results with those of isogenic pairs of susceptible and resistant clinical isolates. Resistance development correlated with
fusA1
mutations
in vitro
and
in vivo. pmrB
mutations, conferring polymyxin resistance, were also frequently selected
in vitro
. In contrast, mutational overexpression of MexXY, a hallmark of aminoglycoside resistance in CF, was not observed in
in vitro
evolution experiments.
Funder
MINECO | Instituto de Salud Carlos III
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
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