title: Potency of SMP-601, a novel carbapenem, in hematogenous murine bronchopneumonia caused by methicillin-resistant and vancomycin-intermediate Staphylococcus aureus.
abstract: We compared the potency of SMP-601, a novel carbapenem, with that of vancomycin in a murine model of hematogenous bronchopneumonia infection caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-intermediate S. aureus (VISA). The MICs of SMP-601 and vancomycin against MRSA were 2 and 1 mug/ml, respectively, while those against VISA were 2 and 8 mug/ml, respectively. Treatment with SMP-601 resulted in a significant decrease in the number of viable bacteria in the MRSA infection model (control, 100 mg/kg vancomycin, and 100 mg/kg SMP-601, 8.42 +/- 0.50, 5.29 +/- 0.71, and 5.50 +/- 0.58 log CFU/lung, respectively,) and in the VISA infection model (control, 100 mg/kg vancomycin, and 100 mg/kg SMP-601, 9.64 +/- 0.63, 8.72 +/- 0.45, 7.42 +/- 0.14 log CFU/lung) (mean +/- standard error of the mean). The survival rate in the VISA infection model treated with SMP-601 (70%) was significantly higher than those in the other two groups (20% for vancomycin and 0% for control; P < 0.05). Histopathological examination revealed that inflammatory changes in the SMP-601-treated group were less marked than in the other two groups. The results of pharmacokinetic-pharmacodynamic analysis supported the results of the bacteriological, histopathological and survival studies. Our results demonstrate the potency of SMP-601 against MRSA and VISA in murine hematogenous pulmonary infection.
authors.affiliation: Department of Pharmacotherapeutics, Nagasaki University Graduate School of Pharmaceutical Sciences, Nagasaki, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Kihara
authors.forename: Katsunori
authors.initials: K
authors.lastname: Yanagihara
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Morinaga
authors.forename: Nobuko
authors.initials: N
authors.lastname: Araki
authors.forename: Shigeki
authors.initials: S
authors.lastname: Nakamura
authors.forename: Masafumi
authors.initials: M
authors.lastname: Seki
authors.forename: Koichi
authors.initials: K
authors.lastname: Izumikawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kakeya
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsukamoto
authors.forename: Shimeru
authors.initials: S
authors.lastname: Kamihira
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D017848:Blood-Borne Pathogens; D001996:Bronchopneumonia / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D015780:Carbapenems / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D006801:Humans; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008297:Male; D016106:Methicillin Resistance; D051379:Mice; D011023:Pneumonia, Staphylococcal / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D013047:Specific Pathogen-Free Organisms; D013211:Staphylococcus aureus / Q000187:drug effects*; D016896:Treatment Outcome; D014640:Vancomycin / Q000494:pharmacology*; D020713:Vancomycin Resistance
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D014640:Vancomycin