title: Mechanism of amikacin resistance in Pseudomonas aeruginosa isolates from patients with cystic fibrosis.
abstract: We studied 27 amikacin-resistant isolates of Pseudomonas aeruginosa from patients with cystic fibrosis to determine the mechanism of antibiotic resistance. The absence of aminoglycoside-modifying enzymes (AMEs) in these isolates was inferred from the failure of DNA probes for 16 candidate AMEs to hybridize with DNA harvested from these isolates and, in addition, the uniform reduction in susceptibility to a panel of aminoglycosides. In eight of the 27 isolates that were resistant to amikacin at high levels (minimum inhibitory concentration > or = 250 micrograms/ml), plasmids were not detected. The ribosomes of these isolates were sensitive to amikacin in studies of protein synthesis by cell "ghosts." These data suggest that impermeability is the mechanism of amikacin resistance in isolates of P. aeruginosa from patients with cystic fibrosis. Recognition of this mode of resistance may be difficult, as some isolates appeared to be borderline susceptible when tested against aminoglycosides other than amikacin, or had zone diameters that overlapped those obtained with amikacin-susceptible isolates.
authors.affiliation: Division of Infectious Disease, Children's Hospital and Medical Center, Seattle, Washington, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Hurley
authors.forename: G H
authors.initials: GH
authors.lastname: Miller
authors.forename: A L
authors.initials: AL
authors.lastname: Smith
mesh_terms: D000583:Amikacin / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003470:Culture Media; D003550:Cystic Fibrosis / Q000382:microbiology; D015342:DNA Probes; D004352:Drug Resistance, Microbial / Q000235:genetics; D006801:Humans; D008826:Microbial Sensitivity Tests; D010641:Phenotype; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification
chemical_list: D000900:Anti-Bacterial Agents; D003470:Culture Media; D015342:DNA Probes; D000583:Amikacin