title: Analysis of amikacin-resistant Pseudomonas aeruginosa developing in patients receiving amikacin.
abstract: During a 36-month period, 28 patients treated for infections due to amikacin-susceptible Pseudomonas aeruginosa subsequently developed infections or colonization with amikacin-resistant P aeruginosa at the same site. Eleven amikacin-susceptible/-resistant pairs of isolates were analyzed for aminoglycoside-inactivating enzymes, plasmid profiles, cellular proteins, outer membrane proteins (OMPs), lipopolysaccharide (LPS) profiles, and amikacin uptake. While clearly distinct from isolates of other patients, sensitive and resistant isolates from the same patients were indistinguishable in plasmid profile, LPS profiles, and OMPs. These results suggest that the resistant P aeruginosa isolates were derived from the sensitive isolates. None of the resistant isolates produced enzymes known to inactivate amikacin. In nine of 11 resistant isolates tested, transport of amikacin into P aeruginosa was reduced. A major mechanism of in vivo development of amikacin resistance in P aeruginosa is alteration in permeability to amikacin, but the aquisition of plasmids or changes in OMPs or LPS profile may not account for this phenomenon.
authors.affiliation: Department of Medicine, Emory University School of Medicine, Atlanta, GA.
authors.forename: J
authors.initials: J
authors.lastname: Maloney
authors.forename: D
authors.initials: D
authors.lastname: Rimland
authors.forename: D S
authors.initials: DS
authors.lastname: Stephens
authors.forename: P
authors.initials: P
authors.lastname: Terry
authors.forename: A M
authors.initials: AM
authors.lastname: Whitney
mesh_terms: D000583:Amikacin / Q000627:therapeutic use*; D001425:Bacterial Outer Membrane Proteins / Q000032:analysis; D001426:Bacterial Proteins / Q000032:analysis; D004352:Drug Resistance, Microbial; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008070:Lipopolysaccharides / Q000032:analysis; D008826:Microbial Sensitivity Tests; D010957:Plasmids; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D008070:Lipopolysaccharides; D000583:Amikacin