title: Activity of imipenem against VIM-1 metallo-beta-lactamase-producing Klebsiella pneumoniae in the murine thigh infection model.
abstract: The in-vivo activity of imipenem against VIM-1-producing Klebsiella pneumoniae (VPKP) was assessed in a thigh infection model in neutropenic mice. Animals were infected with three VPKP isolates (imipenem MICs 2, 4 and 32 mg/L, respectively) and a susceptible clinical isolate (MIC 0.125 mg/L) that did not produce any beta-lactamase with broad-spectrum activity. Bacterial density at the site of infection was determined after imipenem treatment (30 and 60 mg/kg every 2 h for 24 h). The log(10) reduction in CFU/thigh was greatest for the wild-type isolate, intermediate for the two imipenem-susceptible VPKP isolates, and lowest for the imipenem-resistant VPKP isolate. Whilst in-vivo imipenem activity appeared reduced against in-vitro susceptible VIM-1 producers compared with a VIM-1-negative control, an increased drug dosage could moderate this reduction.
authors.affiliation: First Department of Propaedeutic Medicine, Medical School, University of Athens, Athens, Greece.
authors.forename: G L
authors.initials: GL
authors.lastname: Daikos
authors.affiliation: First Department of Propaedeutic Medicine, Medical School, University of Athens, Athens, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Panagiotakopoulou
authors.affiliation: Laboratory of Bacteriology, Hellenic Pasteur Institute, Athens, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Tzelepi
authors.affiliation: Laboratory of Bacteriology, Hellenic Pasteur Institute, Athens, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Loli
authors.affiliation: Department of Microbiology, Medical School, University of Athens, Athens, Greece.
authors.forename: L S
authors.initials: LS
authors.lastname: Tzouvelekis
authors.affiliation: Laboratory of Bacteriology, Hellenic Pasteur Institute, Athens, Greece. Electronic address: miriagou@mail.pasteur.gr.
authors.forename: V
authors.initials: V
authors.lastname: Miriagou
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015378:Imipenem / Q000097:blood / Q000494:pharmacology*; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000201:enzymology* / Q000302:isolation & purification; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D009135:Muscular Diseases / Q000188:drug therapy* / Q000382:microbiology; D009503:Neutropenia / Q000097:blood; D013997:Time Factors; D001618:beta-Lactamases / Q000096:biosynthesis
chemical_list: D000900:Anti-Bacterial Agents; D015378:Imipenem; C417264:VIM-1 metallo-beta-lactamase; D001618:beta-Lactamases