替加环素的抗生素后效应及影响因素的研究

发布时间：2018-08-08 10:39

【摘要】：背景及目的：随着抗菌药物在临床上的广泛应用,尤其是不合理的抗菌药物使用,导致了细菌耐药性的不断产生和增强。目前,耐药菌已经成为院内感染的主要病原菌,严重威胁人类的生命安全,并且给临床治疗带来极大挑战。在此背景下,替加环素于2005年在美国批准上市,作为一种新型甘氨酰环素类抗菌药物,因其具有超广谱的抗菌活性,特别是对多种临床常见耐药菌均具有很高的活性,一经上市,便受到了广泛关注。本文通过研究替加环素对多重耐药的鲍曼不动杆菌(multidrug-resistant acinetobacter baumannii, MDR-AB)、耐甲氧西林的金黄色葡萄球菌(methicillin-resistant Staphylococcus aureus, MRSA)、产超广谱β内酰胺酶(extended-spectrum beta-lactamases, ESBL)的大肠埃希氏菌及大肠埃希氏菌标准菌株ATCC25922的体外抗生素后效应(Post Antibiotic Effect, PAE)及其影响因素,旨在提高广大临床医生对替加环素体外抗菌活性的认识,并且为临床合理用药提供依据。方法：除大肠埃希氏菌标准菌株ATCC25922以外,余待测菌株均来自大连医科大学附属第一医院临床分离株。采用微量肉汤稀释法测定各待测菌株的最低抑菌浓度(MIC),采用平板菌落计数法测定替加环素对各受试菌株的体外PAE,研究各受试菌株分别在各自的1、2.5、5、10倍的MIC药物浓度下分别接触1h、2h时的PAE值,并通过测定替加环素与头孢哌酮钠舒巴坦钠(舒普深)联合用药对MDR-AB的PAE值,来观察联合用药对PAE的影响。结果：本研究发现,替加环素对所有实验菌株均可以产生PAE。替加环素对MDR-AB可产生0.51-2.26h不等的PAE,平均为0.99±0.61h；对ESBL阳性大肠埃希氏菌可产生0.57-2.03h不等的PAE,平均为1.25±0.55h；对MRSA可产生1.59-4.25h不等的PAE,平均值为2.67±0.88h；同时也测定了替加环素对大肠埃希氏菌标准菌株ATCC25922的PAE,其范围在0.66-2.68h之间,平均1.53±0.75h,替加环素对MRSA可产生较长的PAE,与MDR-AB、ESBL阳性大肠埃希氏菌、大肠杆菌标准菌株相比,差异具有显著统计学意义(P0.01),而其余受试菌株之间差异无统计学意义(P0.05)。本研究中,所有受试菌株均表现出随着接触时间的增加,PAE值也随之延长,其中ESBL阳性大肠埃希氏菌、MRSA及ATCC25922的差异均有统计学意义(P0.05),而对于MDR-AB,虽然PAE随时间延长而增加,但差异无统计学意义(P0.05)：PAE随着药物浓度的增加而延长,对于多数受试菌株,不同浓度间PAE相比,差异有统计学意义(P0.05)。替加环素、舒普深单独用药时对MDR-AB的PAE的分别为0.37、0.73h,联合用药后的PAE为1.23h,两种抗菌药物表现出相加作用。结论：1.替加环素对MDR-AB、MRSA、ESBL阳性大肠埃希氏菌、大肠埃希氏菌标准株ATCC25922可产生0.51-4.25h不等的PAE。2.替加环素对MRSA的PAE明显长于对MDR-AB、ESBL日性大肠埃希氏菌、ATCC25922的PAE,差异均有统计学意义(P0.05)。3.替加环素对各实验菌株的PAE值随着药物浓度、接触时间的增加而延长。4.替加环素对大肠埃希氏菌标准株ATCC25922可产生较ESBL阳性大肠埃希氏菌长的PAE,但二者之间无统计学差异(P0.05)。5.替加环素与舒普深联合应用作用于MDR-AB时测PAE值,表现为相加作用。提示二者联合有助于临床加强抗MDR-AB的疗效。
[Abstract]:Background and purpose: with the widespread use of antimicrobial agents in the clinic, especially the use of irrational antibiotics, the drug resistance has been produced and enhanced. At present, drug resistant bacteria have become the main pathogens of nosocomial infection, which seriously threaten the safety of human life and bring great challenges to clinical treatment. In 2005, tegicycline was approved to be listed in the United States. As a new type of glycyl cyclin antibacterial agent, because of its super broad-spectrum antimicrobial activity, especially for a variety of clinical common drug resistant bacteria, it has been widely paid attention to. This paper has studied the multidrug resistance of tegacycline to the Bauman immobile. Multidrug-resistant Acinetobacter baumannii (MDR-AB), methicillin resistant Staphylococcus aureus (methicillin-resistant Staphylococcus aureus, MRSA), and in vitro antibiotics of Escherichia coli and Escherichia coli (extended-spectrum beta-lactamases, ESBL) and standard strains of Escherichia coli. Post Antibiotic Effect (PAE) and its influencing factors are designed to improve the understanding of the antibacterial activity of tegocycline in vitro and provide the basis for clinical rational use. Methods: except for the standard Escherichia coli strain, ATCC25922, the remaining strains were isolated from the clinical isolation of the First Affiliated Hospital of Dalian Medical University. The minimum inhibitory concentration (MIC) of each strain was measured with the dilution method of broth, and the PAE of tegacycline was measured by plate colony counting method in vitro. The PAE values of the tested strains were respectively exposed to 1H and 2H at the 1,2.5,5,10 times of the MIC drug concentration in their respective 1,2.5,5,10 times, and by the determination of tegacycline and cefperidin. The effect of combined use of sodium ketone sodium sulbactam sodium (Shu Pushen) on the PAE value of MDR-AB was observed. Results: This study found that tegocyclin could produce PAE with PAE. tegocycline for MDR-AB to produce 0.51-2.26h unequal to MDR-AB, averaging 0.99 + 0.61h; 0.57-2.03 for ESBL positive Escherichia coli could produce 0.57-2.03. The average PAE of H is 1.25 + 0.55h, and MRSA can produce PAE with unequal 1.59-4.25h, and the average value is 2.67 + 0.88h. Meanwhile, the PAE of the standard strain of tegocyclin against the standard Escherichia coli strain ATCC25922 is also measured. The range is between 0.66-2.68h, and the average of 1.53 + 0.75h. There was significant difference in the difference between the standard strains of Escherichia coli and Escherichia coli (P0.01), but there was no significant difference between the other strains (P0.05). In this study, all the tested strains showed that the PAE value increased with the increase of contact time, including the difference of ESBL positive Escherichia coli, MRSA and ATCC25922. There were statistical significance (P0.05), but for MDR-AB, although PAE increased with time, the difference was not statistically significant (P0.05):PAE with the increase of drug concentration, and for most of the strains, the difference was statistically significant (P0.05) compared with PAE (P0.05). 0.37,0.73h, the PAE of the combined drug was 1.23h, and the two kinds of antibiotics showed additive effect. Conclusion: 1. tegocycline can produce MDR-AB, MRSA, ESBL positive Escherichia coli and Escherichia coli standard strain ATCC25922 to produce 0.51-4.25h unequal PAE.2. tegocyclin for MRSA PAE obviously longer than that of MDR-AB, Escherichia coli. 5922 PAE, the difference was statistically significant (P0.05) the PAE value of tegocyclin to the experimental strains was increased with the concentration of drug and the increase of contact time,.4. tegocycline could produce a PAE of ESBL positive Escherichia coli longer than ESBL positive Escherichia coli, but there was no statistical difference between the two (P0.05).5. tegocyclin. The combination of Shupushen and MDR-AB can increase the PAE value of MDR-AB.
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R96

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