Clinic of Infectious Diseases, Department of Biomedical Sciences, Università Politecnica delle Marche, Ancona, Italy.
Peptides. 2011 Apr;32(4):697-701. doi: 10.1016/j.peptides.2011.01.016. Epub 2011 Jan 22.
An experimental study was performed to evaluate the interaction between s-thanatin and colistin both in vitro and in vivo, using two Pseudomonas aeruginosa strains with different patterns of susceptibilities. We evaluated whether selecting for colistin-resistant P. aeruginosa could be prevented in vitro by combining colistin with s-thanatin. The strains were serially exposed in broth to twofold stepwise increasing concentrations of colistin alone or in combination with a fixed concentration [0.25× minimum inhibitory concentration (MIC)] of s-thanatin. We also performed an in vitro synergy study. For in vivo studies, a mouse model of Pseudomonas sepsis has been used. Main outcome measures were lethality and quantitative blood cultures. Exposure to colistin alone gradually selected for Pseudomonas strains with an increased MIC. In vitro studies, s-thanatin showed a positive interaction with colistin, and was able to prevent its resistance. In vivo studies, s-thanatin combined with colistin exhibited the highest efficacy on all main outcome measurements. These results highlight the potential usefulness of this combination and provide a future therapeutic alternative in severe Pseudomonas infections.
一项实验研究评估了 s-Thanatin 和黏菌素在体外和体内的相互作用，使用了两种对两种不同模式敏感的铜绿假单胞菌菌株。我们评估了在体外通过将黏菌素与 s-Thanatin 联合使用是否可以防止选择耐黏菌素的铜绿假单胞菌。这些菌株在肉汤中连续暴露于两倍递增浓度的黏菌素单独或与固定浓度[0.25×最小抑菌浓度（MIC）]的 s-Thanatin 联合。我们还进行了体外协同研究。在体内研究中，使用了铜绿假单胞菌脓毒症的小鼠模型。主要观察指标为死亡率和定量血培养。单独接触黏菌素逐渐选择出 MIC 增加的铜绿假单胞菌菌株。体外研究表明，s-Thanatin 与黏菌素呈正相互作用，并能防止其耐药性。体内研究表明，s-Thanatin 联合黏菌素在所有主要观察指标上均显示出最高的疗效。这些结果突出了这种组合的潜在有用性，并为严重铜绿假单胞菌感染提供了未来的治疗选择。
