title: The therapeutic effect of tigecycline, unlike that of Ceftazidime, is not influenced by whether the Klebsiella pneumoniae strain produces extended-spectrum β-lactamases in experimental pneumonia in rats.
abstract: The efficacies of tigecycline and ceftazidime against fatal pneumonia in rats caused by an extended-spectrum β-lactamase (ESBL)-positive Klebsiella pneumoniae strain or its wild-type (WT) progenitor were compared. Ceftazidime at 12.5 or 50 mg/kg of body weight twice daily (b.i.d.) was effective (50% or 100% rat survival) in pneumonia caused by the WT isolate but unsuccessful (100% rat mortality) in pneumonia caused by the ESBL-positive variant. In contrast, tigecycline at 6.25, 12.5, or 25 mg/kg b.i.d. showed dosage-dependent efficacy up to 100% rat survival irrespective of the ESBL character of the infecting organism.
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands. w.goessens@erasmusmc.nl
authors.forename: Wil H F
authors.initials: WH
authors.lastname: Goessens
authors.forename: Johan W
authors.initials: JW
authors.lastname: Mouton
authors.forename: Marian T
authors.initials: MT
authors.lastname: Ten Kate
authors.forename: Fritz
authors.initials: F
authors.lastname: Sörgel
authors.forename: Martina
authors.initials: M
authors.lastname: Kinzig
authors.forename: Irma A J M
authors.initials: IA
authors.lastname: Bakker-Woudenberg
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D002442:Ceftazidime / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007710:Klebsiella Infections / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000254:growth & development; D008168:Lung / Q000187:drug effects* / Q000382:microbiology; D008297:Male; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D018410:Pneumonia, Bacterial / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D051381:Rats; D016019:Survival Analysis; D000078304:Tigecycline; D001618:beta-Lactamases / Q000096:biosynthesis*
chemical_list: D000900:Anti-Bacterial Agents; D000078304:Tigecycline; D002442:Ceftazidime; D001618:beta-Lactamases; D008911:Minocycline