title: Aminoglycoside-resistance mechanisms for cystic fibrosis Pseudomonas aeruginosa isolates are unchanged by long-term, intermittent, inhaled tobramycin treatment.
abstract: Aminoglycoside-resistance mechanisms were characterized in Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients during a recent clinical trial of inhaled tobramycin. Impermeability, in which bacteria have reduced susceptibility to all aminoglycosides, was the predominant mode of resistance in isolates obtained both before and after 6 months of cyclic treatment with tobramycin or placebo administered by aerosol. Enzymatic resistance mechanisms were found in fewer than 10% of resistant isolates. P. aeruginosa from individual patients could be grouped on the basis of genetic relatedness. When enzymatic resistance was involved, all isolates in a group had elevated tobramycin MICs. When impermeability occurred, MICs of a genotypic group varied from susceptible to resistant. These findings suggest that impermeability resistance occurs in only a fraction of the P. aeruginosa population in lungs of persons with CF and that this form of resistance arises by a process involving multiple small changes in MIC.
authors.affiliation: Department of Research Biology, PathoGenesis Corp., Seattle, WA 98119, USA. dmacleod@pathogenesis.com
authors.forename: D L
authors.initials: DL
authors.lastname: MacLeod
authors.forename: L E
authors.initials: LE
authors.lastname: Nelson
authors.forename: R M
authors.initials: RM
authors.lastname: Shawar
authors.forename: B B
authors.initials: BB
authors.lastname: Lin
authors.forename: L G
authors.initials: LG
authors.lastname: Lockwood
authors.forename: J E
authors.initials: JE
authors.lastname: Dirk
authors.forename: G H
authors.initials: GH
authors.lastname: Miller
authors.forename: J L
authors.initials: JL
authors.lastname: Burns
authors.forename: R L
authors.initials: RL
authors.lastname: Garber
mesh_terms: D000280:Administration, Inhalation; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003550:Cystic Fibrosis / Q000382:microbiology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D014031:Tobramycin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D014031:Tobramycin