In vitro activity of tebipenem, a new oral carbapenem antibiotic, against penicillin-nonsusceptible Streptococcus pneumoniae
In vitro activity of tebipenem, a new oral carbapenem antibiotic, against penicillin-nonsusceptible Streptococcus pneumoniae
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DOI：
10.1128/aac.49.3.889-894.2005
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发表时间：
2005-03-01
影响因子：
4.9
通讯作者：
Ubukata, K
中科院分区：
文献类型：
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作者：
Kobayashi, R;Konomi, M;Ubukata, K
将特比培南 (TBM)（一种新型口服碳青霉烯类抗生素）针对肺炎链球菌临床分离株 (n = 202) 的体外活性与 15 种参考药物的体外活性进行了比较。 PCR 鉴定异常 pbp1a、pbp2x 和 pbp2b 基因后，将分离株分为五个基因型类别：(i) 青霉素敏感肺炎链球菌 (PSSP) 分离株，无异常 pbp 基因 (n = 34；16.8%)，(ii) 基因型青霉素中间型肺炎链球菌 (gPISP) 分离株，仅具有异常 pbp2x 基因 [gPISP。 (2x)] (n = 48; 23.8%)，(iii) 具有异常 pbp1a 和 pbp2x 基因的 gPISP 分离株 (n = 32; 15.8%)，(iv) 具有异常 pbp2x 和 pbp2b 基因的 gPISP 分离株 (n = 16; 7.9%)，以及 (v) 具有 3 个异常的基因型耐青霉素肺炎链球菌 (gPRSP) 分离株pbp 基因（n = 72；35.6%）。大多数测试菌株具有 mefA (n = 59; 29.2%) 或 ermB (n = 91; 45%) 基因介导的大环内酯耐药性。对于这些分离株，TBM 抑制 90% 分离株的 MIC 显着低于参考口服抗生素，如下：PSSP 为 0.002 微克/毫升，gPISP (2x) 为 0.004 微克/毫升，gPISP 为 0.016 微克/毫升（具有异常 pbp1a 和 pbp2x 基因的分离株以及具有异常 pbp2x 和 pbp2b 基因的分离株），以及gPRSP 为 0.063 杯/毫升。此外，TBM对gPRSP分离株表现出优异的杀菌活性，当它们与大于或等于MIC的浓度一起孵育时，在2小时内表现出3-log(10)下降。短期暴露于 TBM 后，通过扫描电子显微镜观察到细胞壁合成向长轴方向的抑制以及随后的细胞裂解，这与头孢菌素所观察到的效果不同。这些数据表明，TBM 对多重耐药肺炎链球菌（社区获得性呼吸道感染的致病病原体）具有强大的活性。
The in vitro activity of tebipenem (TBM), a new oral carbapenem antibiotic, against Streptococcus pneumoniae clinical isolates (n = 202) was compared with those of 15 reference agents. The isolates were classified into five genotypic classes after PCR identification of abnormal pbp1a,pbp2x, and pbp2b genes: (i) penicillin-susceptible S. pneumoniae (PSSP) isolates with no abnormal pbp genes (n = 34; 16.8%), (ii) genotypic penicillin-intermediate S. pneumoniae (gPISP) isolates with only an abnormal pbp2x gene [gPISP. (2x)] (n = 48; 23.8%), (iii) gPISP isolates with abnormal pbp1a and pbp2x genes (n = 32; 15.8%), (iv) gPISP isolates with abnormal pbp2x and pbp2b genes (n = 16; 7.9%), and (v) genotypic penicillin-resistant S. pneumoniae (gPRSP) isolates with three abnormal pbp genes (n = 72; 35.6%). The majority of the strains tested had mefA (n = 59; 29.2%) or ermB (n = 91; 45%) gene-mediating macrolide resistance. For these isolates the MIC at which 90% of isolates are inhibited was significantly lower for TBM than for the reference oral antibiotics, as follows: 0.002 mug/ml for PSSP, 0.004 mug/ml for gPISP (2x), 0.016 mug/ml for gPISP (isolates with abnormal pbp1a and pbp2x genes and isolates with abnormal pbp2x and pbp2b genes), and 0.063 mug/ml for gPRSP. In addition, TBM showed excellent bactericidal activity against gPRSP isolates, which exhibited a 3-log(10) decrease within 2 h when they were incubated with a concentration greater than or equal to the MIC. Inhibition of cell wall synthesis toward the long axis and subsequent cell lysis were observed by scanning electron microscopy after a short-term exposure to TBM, unlike the effects seen with cephalosporins. These data suggest that TBM has potent activity against multidrug-resistant S. pneumoniae, the causative pathogen of community-acquired respiratory tract infections.