Dandekar Prachi K, Tessier Pamela R, Farrell David J, Nightingale Charles H, Nicolau David P
Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT 06102, USA.
Int J Antimicrob Agents. 2005 Oct;26(4):331-4. doi: 10.1016/j.ijantimicag.2005.07.013.
In a recent study, our in vivo data suggested that clinically achievable levels of telithromycin are more effective than azithromycin against selected Streptococcus pneumoniae isolates with ribosomal mutations in 23S rRNA gene alleles and L22 region mutations. In the current study, we attempt to investigate further the antibacterial activity of telithromycin against these isolates to better delineate the disparity between isolates based on allelic differences. Four isolates of S. pneumoniae with ribosomal mutations were tested using in vitro time-kill methodology. Isolates were exposed to telithromycin at concentrations of 0.5-8 x the minimum inhibitory concentration (MIC). At these exposures, telithromycin demonstrated concentration-dependent killing for three of the four isolates. Against the fourth isolate, telithromycin affected only a 1 log decrease in colony-forming units/mL despite exposures of 8 x MIC. These data demonstrate the in vitro killing profile of telithromycin against S. pneumoniae isolates with ribosomal and L22 mutations. Whilst telithromycin did not demonstrate bactericidal activity against all isolates in these time-kill studies, the in vivo human-simulated exposures did result in a high degree of bacterial kill. Full evaluation of the potential utility of new antimicrobial agents against these emerging genotypic profiles requires both in vitro and in vivo assessments.
在最近一项研究中，我们的体内数据表明，对于在23S rRNA基因等位基因中存在核糖体突变以及L22区域突变的特定肺炎链球菌分离株，临床可达到的替利霉素水平比阿奇霉素更有效。在当前研究中，我们试图进一步研究替利霉素对这些分离株的抗菌活性，以便根据等位基因差异更好地描述分离株之间的差异。使用体外时间杀菌方法对4株具有核糖体突变的肺炎链球菌分离株进行了测试。将分离株暴露于浓度为最低抑菌浓度（MIC）的0.5 - 8倍的替利霉素中。在这些暴露条件下，替利霉素对4株分离株中的3株表现出浓度依赖性杀菌作用。对于第4株分离株，尽管暴露于8倍MIC的替利霉素中，其菌落形成单位/mL仅减少了1个对数。这些数据证明了替利霉素对具有核糖体和L22突变的肺炎链球菌分离株的体外杀菌情况。虽然在这些时间杀菌研究中替利霉素并未对所有分离株都表现出杀菌活性，但在体内模拟人体暴露确实导致了高度的细菌杀灭。对新型抗菌药物针对这些新出现的基因型的潜在效用进行全面评估需要进行体外和体内评估。
