title: Persistence of Pseudomonas aeruginosa during ciprofloxacin therapy of a cystic fibrosis patient: transient resistance to quinolones and protein F-deficiency.
abstract: The mechanism of persistence was characterized in Pseudomonas aeruginosa isolates obtained ten days before (4405), on the tenth day of (4419), and four days after (4478) ciprofloxacin therapy in a cystic fibrosis patient. Isolate 4419 showed a 16-fold increase in resistance to ciprofloxacin, norfloxacin and nalidixic acid. The outer membrane of 4419 had no detectable protein F. A modified lipopolysaccharide profile, a longer lag phase before growth and a slower generation time were also noted for isolate 4419. Cell surface hydrophobicity was increased by 20% in 4419 whereas uptake of [14C]ciprofloxacin was equivalent in all three isolates. Ciprofloxacin doses causing 50% inhibition of DNA synthesis were proportional to MICs for each isolate indicating that the DNA gyrase of 4419 was resistant to quinolones. A quinolone-susceptible revertant of 4419 remained deficient in protein F. Protein F-deficiency was not associated with resistance to quinolones, nor to other antibiotics, supporting the view that it plays little role in outer membrane permeability to antibiotics.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: S
authors.initials: S
authors.lastname: Chamberland
authors.forename: F
authors.initials: F
authors.lastname: Malouin
authors.forename: H R
authors.initials: HR
authors.lastname: Rabin
authors.forename: T
authors.initials: T
authors.lastname: Schollaardt
authors.forename: T R
authors.initials: TR
authors.lastname: Parr
authors.forename: L E
authors.initials: LE
authors.lastname: Bryan
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000494:pharmacology*; D000911:Antibodies, Monoclonal; D001425:Bacterial Outer Membrane Proteins / Q000096:biosynthesis*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002939:Ciprofloxacin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003470:Culture Media; D003550:Cystic Fibrosis / Q000382:microbiology*; D015342:DNA Probes; D004269:DNA, Bacterial / Q000032:analysis / Q000096:biosynthesis; D004352:Drug Resistance, Microbial; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008070:Lipopolysaccharides / Q000302:isolation & purification; D008297:Male; D009124:Muscle Proteins / Q000172:deficiency*; D025203:Phosphofructokinase-1, Muscle Type; D025221:Phosphofructokinases; D011506:Proteins; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics
chemical_list: D000890:Anti-Infective Agents; D000911:Antibodies, Monoclonal; D001425:Bacterial Outer Membrane Proteins; D003470:Culture Media; D015342:DNA Probes; D004269:DNA, Bacterial; D008070:Lipopolysaccharides; D009124:Muscle Proteins; D011506:Proteins; D002939:Ciprofloxacin; D025221:Phosphofructokinases; D025203:Phosphofructokinase-1, Muscle Type; C026043:PFKM protein, human