title: Rapid emergence of resistance in Pseudomonas aeruginosa in cystic fibrosis patients due to in-vivo selection of stable partially derepressed beta-lactamase producing strains.
abstract: The development of significant mechanisms of resistance to beta-lactam antibiotics in Pseudomonas aeruginosa in cystic fibrosis (CF) patients have been studied in ten CF patients during a two week course of anti-pseudomonal beta-lactam antibiotic therapy. Sputum samples were collected on days 1, 7 and 15. Entire homogenized sputum samples were examined directly for the number of bacteria resistant to different levels of antibiotics. This allowed the detection of pre-existing resistant subpopulations of bacteria as well as following the changes in beta-lactam antibiotic susceptibility during treatment. P. aeruginosa isolates were characterized by means of sero-grouping, phage- and pyocin-typing. Outer membrane proteins of paired sensitive and resistant strains were characterized. Sonicated extracts of cells were assayed for basal and induced beta-lactamase activity. Beta-lactamase activity was further characterized by isoelectric focusing and inhibition profiles. Our observations were in accordance with the hypothesis that the sensitive inducible population was overrun by the pre-existing resistant subpopulation, during treatment. The resistant in-vivo selected P. aeruginosa population exhibited stable partially derepression but the beta-lactamase inhibitor tazobactam restored beta-lactam antibiotic activity.
authors.affiliation: Institute of Medical Microbiology, University of Copenhagen, Denmark.
authors.forename: B
authors.initials: B
authors.lastname: Giwercman
authors.forename: P A
authors.initials: PA
authors.lastname: Lambert
authors.forename: V T
authors.initials: VT
authors.lastname: Rosdahl
authors.forename: G H
authors.initials: GH
authors.lastname: Shand
authors.forename: N
authors.initials: N
authors.lastname: Høiby
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D002648:Child; D003550:Cystic Fibrosis / Q000378:metabolism / Q000382:microbiology*; D004352:Drug Resistance, Microbial; D005260:Female; D006801:Humans; D008297:Male; D010397:Penicillanic Acid / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D013183:Sputum / Q000382:microbiology; D000078142:Tazobactam; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D065093:beta-Lactamase Inhibitors; D010397:Penicillanic Acid; D001618:beta-Lactamases; D000078142:Tazobactam