Potency of SMP-601, a Novel Carbapenem, in Hematogenous Murine Bronchopneumonia Caused by Methicillin-Resistant and Vancomycin-Intermediate Staphylococcus aureus | Zendy

Rie Kihara | Zendy; Katsunori Yanagihara | Zendy; Yoshitomo Morinaga | Zendy; Nobuko Araki | Zendy; Shigeki Nakamura | Zendy; Masafumi Seki | Zendy; Koichi Izumikawa | Zendy; Hiroshi Kakeya | Zendy; Yoshihiro Yamamoto | Zendy; Kazuhiro Tsukamoto | Zendy; Shimeru Kamihira | Zendy; Shigeru Kohno | Zendy

Open Access

Potency of SMP-601, a Novel Carbapenem, in Hematogenous Murine Bronchopneumonia Caused by Methicillin-Resistant and Vancomycin-Intermediate Staphylococcus aureus

Author(s) -

Rie Kihara,

Katsunori Yanagihara,

Yoshitomo Morinaga,

Nobuko Araki,

Shigeki Nakamura,

Masafumi Seki,

Koichi Izumikawa,

Hiroshi Kakeya,

Yoshihiro Yamamoto,

Kazuhiro Tsukamoto,

Shimeru Kamihira,

Shigeru Kohno

Publication year - 2008

Publication title -

antimicrobial agents and chemotherapy

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.07

H-Index - 259

eISSN - 1070-6283

pISSN - 0066-4804

DOI - 10.1128/aac.01532-07

Subject(s) - vancomycin , staphylococcus aureus , potency , methicillin resistant staphylococcus aureus , microbiology and biotechnology , medicine , pharmacodynamics , carbapenem , staphylococcal infections , pharmacokinetics , antibiotics , biology , bacteria , in vitro , biochemistry , genetics

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.

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