慢性感染临床微生物样本中持留菌的特性研究

Characteristics of Persisters Isolated from Chronic Infected Patients

目的：了解慢性感染患者微生物样本中持留菌的持留特性，明确持留菌与感染时间及抗生素之间的关系。方法将41株持留菌分离株（4株大肠埃希菌，23株肺炎克雷伯菌，8株铜绿假单胞菌，6株金黄色葡萄球菌）置于不同抗生素种类和浓度（10×MIC，50×MIC和100×MIC）以及营养不足的生长条件下，通过其在各环境中的特异性生长曲线分析其持留水平。结果随着抗生素浓度增加，持留菌比例逐渐下降，抗生素浓度到达100 MIC其本可以将持留菌全部清除；同一株持留菌对不同抗生素的持留水平不同，其中大肠埃希菌对头孢噻肟的持留水平最低，肺炎克雷伯菌对环丙沙星的持留水平最低，铜绿假单胞菌对左氧氟沙星的持留水平最低，金黄色葡萄球菌对亚胺培南的持留水平最低；持留菌对于营养不足的生长条件耐受明显要高于对照株（存活率10^－3：10^－6，P＜0.05）；用独立样本的单因素方差分析同一患者不同感染时期持留菌的持留水平差异没有统计学意义（P＞0.05）。结论持留株对不同种类和浓度的抗生素具有不同的耐受能力。这为深入了解持留菌与慢性感染的关系、持留菌在临床中的不同持留特性提供了重要信息。

Objective To investigate the characteristics of persisters isolated from the chronic infected patients and clarify the relationship between the infection time and persistence as well as antibiotic drugs,so as to provide scientific basis for clinical effective measures to prevent,control and treatment of persister-associated chronic infection.Methods The tolerant ability of the 41 persisters （4 strains of Escherichiacoli,23 strains of Klebsiellapneumoniae,8 strains of Pseudomonasaeruginosa and 6 strains of Staphylococcusaureus）under differet kind and concentration of antibiotics and nutritional deficiencies cindi-tions were detected.In addition,analysis of the homologous strains isolated from the same patients with different infection time was performed.Results The study found that with the increase of concentration of antibiotics,the proportion of persis-ters would gradually decrease.The tolerance ability of the same persister strain to different antibiotics was dissimilar,and different species persisters also had various tolerance ability to the same kind of antibiotics.Persisters were more able to withstand the lack of nutrition.What’s more,there is no significant difference between the resistant ability of the homolo-gous strains isolated from the same patients with different infection time （P〉0.05）.Conclusion Persisters have different a-bility to stand the kill of different kinds and concentration of antibiotics and they can even be completely removed when ex-posed to sufficiently high concentrations of antibiotic.