Potency of SMP-601, a novel carbapenem, in hematogenous murine bronchopneumonia caused by methicillin-resistant and vancomycin-intermediate Staphylococcus aureus

被引:14
作者
Kihara, Rie [1 ,2 ]
Yanagihara, Katsunori [2 ,3 ]
Morinaga, Yoshitomo [2 ,3 ]
Araki, Nobuko
Nakamura, Shigeki [3 ]
Seki, Masafumi [3 ]
Izumikawa, Koichi [3 ]
Kakeya, Hiroshi [3 ]
Yamamoto, Yoshihiro
Tsukamoto, Kazuhiro [1 ]
Kamihira, Shimeru [2 ]
Kohn, Shigeru
机构
[1] Nagasaki Univ, Grad Sch Pharmaceut Sci, Dept Pharmacotherapeut, Nagasaki 8528501, Japan
[2] Nagasaki Univ, Grad Sch Med Sci, Dept Lab Med, Nagasaki 8528501, Japan
[3] Nagasaki Univ, Grad Sch Med Sci, Dept Internal Med 2, Nagasaki 8528501, Japan
关键词
D O I
10.1128/AAC.01532-07
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 mu g/ml, respectively, while those against VISA were 2 and 8 mu g/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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收藏
页码:2163 / 2168
页数:6
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