title: Efficacy of tigecycline vs. imipenem in the treatment of experimental Acinetobacter baumannii murine pneumonia.
abstract: The in vivo activity of tigecycline was evaluated in an experimental pneumonia model (C57BL/6 mice) by Acinetobacter baumannii. Two clinical strains were used: minimum inhibitory concentrations (MICs) of imipenem and tigecycline 1 and 2 microg/mL (imipenem-susceptible, IPM-S), and 8 and 2 microg/mL (imipenem-intermediate, IPM-I), respectively. For imipenem (30 mg/Kg), T/CMI (h) were 1.04 and 0.51 for IPM-S and IPM-I, respectively. For tigecycline (5 mg/Kg), the area under the concentration-time curve (AUC)/MIC(0-24 h) (serum and lung) were 9.24 and 4.37 (for the two strains), respectively. In the efficacy experiments with the IPM-S, imipenem (log CFU/g 3.59 +/- 0.78, p = 0.006) and tigecycline (2.82 +/- 1.2, p = 0.054) decreased the bacterial counts in lungs with respect to its controls; with the IPM-I, both imipenem (1.21 +/- 0.52, p = 0.002) and tigecycline (3.21 +/- 0.28, p = 0.035) decreased the bacterial counts with respect to the controls. In the survival experiments, with the IPM-S, the mortality was the same in the control (67%) and in the tigecycline (77%) groups, and imipenem reduced it (21%, p = 0.025); with the IPM-I, the mortality was the same in the control (87%) and in the tigecycline (85%) groups, and imipenem (0%) reduced it (p < 0.001). In summary, the present study shows that tigecycline is less efficacious than imipenem in the treatment of experimental A. baumannii pneumonia caused by IPM-S and IPM-I strains.
authors.affiliation: Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Seville, Spain. cristina.pichardo.exts@juntadeandalucia.es
authors.forename: C
authors.initials: C
authors.lastname: Pichardo
authors.forename: M E
authors.initials: ME
authors.lastname: Pachón-Ibañez
authors.forename: F
authors.initials: F
authors.lastname: Docobo-Perez
authors.forename: R
authors.initials: R
authors.lastname: López-Rojas
authors.forename: M E
authors.initials: ME
authors.lastname: Jiménez-Mejías
authors.forename: A
authors.initials: A
authors.lastname: Garcia-Curiel
authors.forename: J
authors.initials: J
authors.lastname: Pachon
mesh_terms: D000151:Acinetobacter Infections / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000187:drug effects*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D004195:Disease Models, Animal; D005260:Female; D015378:Imipenem / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D008168:Lung / Q000737:chemistry / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008911:Minocycline / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D018410:Pneumonia, Bacterial / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology; D018709:Statistics, Nonparametric; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D000078304:Tigecycline; D015378:Imipenem; D008911:Minocycline