【作者】 张冰；

【导师】 甄清；

【作者基本信息】 吉林大学 ， 公共卫生， 2011， 硕士

【摘要】 早在1928年,青霉素被英国医学家弗莱明所发现,从此结束了感染性疾病无抗菌药物治疗的时代。随着时代的发展,各种抗菌药物快速开发并广泛用于各类感染性疾病的治疗,有效地控制了这类疾病,延长了患者的寿命,对提高患者的生活质量起到了积极作用。但是细菌的耐药性问题又给临床治疗带来了新的难题。特别是革兰阴性杆菌耐药问题已成为全社会共同关注的公共卫生问题。为了控制细菌耐药的产生和蔓延,目前全球都在进行各种规模的细菌耐药监测工作,如美国建立国家级医院感染监测系统(NNIS)、世界30多个国家参与的SENTRY抗菌药物监测项目、欧洲建立了欧洲细菌耐药监测系统(EARSS)等。而我国也正在进行各种规模的细菌耐药监测工作,如全国细菌耐药监测网(Mohnarin)、全国细菌分离物耐药性Etest和琼脂稀释法监测(SEANIR)、中国CHINET细菌耐药监测等。由于不同地区应用抗菌药物都有各自不同的习惯,所以细菌的耐药性的产生和发展也各有不同。有资料显示,不同国家、不同地区、不同医院甚至同一医院的不同科室的细菌耐药率存在很大差异。因此,了解本地区、本单位的细菌的分布特点及耐药监测结果对临床医生正确使用抗菌药物,减少和延缓耐药菌株的出现,有效地控制耐药菌株的流行非常重要。为了解我院2009-2010年临床分离的革兰阴性杆菌的分布特点和耐药状况,为临床合理应用抗菌药物提供依据,本研究收集了2009年1月-2010年12月间从临床分离革兰阴性杆菌1171株(剔除同一病人相同部位分离的重复菌株),采用法国生物梅里埃的API鉴定系统和Vitek-compact鉴定系统进行菌种的鉴定。药物敏感性试验采用纸片扩散法(Kirby-bauer法)根据CLSI M100规定的标准判读结果。用WHONET5.3软件及SPSS13.0软件进行结果统计与分析。研究结果显示,2009年1月-2010年12月临床分离出革兰阴性杆菌1171株,其中2009年分离出革兰阴性杆菌689株,位居前五位的病原菌依次为克雷伯菌属、鲍曼不动杆菌、铜绿假单胞菌、阴沟肠杆菌、大肠埃希菌;2010年分离出革兰阴性杆菌482株,位居前五位的病原菌依次为克雷伯菌属、鲍曼不动杆菌、铜绿假单胞菌、大肠埃希菌、嗜麦芽窄食单胞菌。病原菌的主要科室来源为呼吸内科、ICU,病原菌主要标本来源为痰标本。除了克雷伯菌属、沙雷菌属、鲍曼不动杆菌、铜绿假单胞菌对部分抗菌药物2009年与2010年的耐药率有差异(P<0.05)外,其它革兰阴性杆菌对抗菌药物2009年与2010年的耐药率没有有明显差异(P>0.05)。对肠杆菌科细菌来讲,只有哌拉西林/他唑巴坦、头孢哌酮/舒巴坦、亚胺培南、美罗培南保持有良好的抗菌活性,但也存在一定的耐药性,耐药率在0.0%-17.0%之间,对其它β-内酰胺类抗菌药物存在很高的耐药率,这可能与产生碳氢霉烯酶、Ampc金属酶、超广谱β-内酰胺酶有关。大肠埃希菌对环丙沙星的耐药率大于73.6%,而其它肠杆菌科细菌对环丙沙星的耐药率多数在15.0%-23.0%之间。对肠杆菌科细菌来讲,对阿米卡星的耐药率明显低于对庆大霉素的耐药率,这可能与阿米卡星临床应用很少且它有很强的耐酶性有关。对非发酵革兰阴性杆菌来讲,鲍曼不动杆菌多重耐药状况严重,鲍曼不动杆菌除了对头孢哌酮/舒巴坦2009年与2010年的耐药率有差异(P<0.05)外,对其他抗菌药物没有明显差异。并且只有头孢哌酮/舒巴坦有好的抗菌活性。在2009年检出17株泛耐药菌株,在2010年检出24株泛耐药菌株。产生耐药现象严重的原因可能与产生超广谱β-内酰胺酶、Ampc酶、碳氢霉烯酶等各种β-内酰胺酶,产生氨基糖苷钝化酶、gyrA\parC基因的突变等有关。铜绿假单胞菌、嗜麦芽窄食单胞菌对抗菌药物的耐药率大部分低于20.0%。产生这一现象的原因可能是由于我院医生用药起点低或者医生采用轮换用药策略运用得好或者是多来源于定植菌等的原因。对于ICU与非ICU分离的肠杆菌科细菌来讲,只有阴沟肠杆菌对替卡西林/克拉维酸的耐药率有差异(P<0.05)。除了对阴沟肠杆菌以外,对其它肠杆菌科细菌抗菌活性最强的是亚胺培南、美罗培南,其次是对哌拉西林/他唑巴坦、头孢哌酮/舒巴坦、阿米卡星,抗菌活性最差的是氨苄西林。对于ICU与非ICU分离的非发酵革兰阴性杆菌来讲,ICU的鲍曼不动杆菌对大部分抗菌药物的耐药率明显高于非ICU的鲍曼不动杆菌对大部分抗菌药物的耐药率,它们之间存在差异,具有统计学意义(P<0.05)。对鲍曼不动杆菌来讲,只有头孢哌酮/舒巴坦的抗菌活性最好,其余大部分抗菌药物对鲍曼不动杆菌都处于高耐药状态。造成这一现状的原因是由于入住ICU的患者有使用气管插管、气管切开及呼吸机的使用等侵入性操作机率高,再加上住院时间久,基础疾病严重,长期应用大量的广谱抗菌药物等共性。本研究表明,我院分离的革兰阴性杆菌耐药状况非常严重,仅有哌拉西林/他唑巴坦、头孢哌酮/舒巴坦、亚胺培南、美罗培南、阿米卡星等少数几种抗菌药物存在好的抗菌活性。来源于ICU与非ICU的鲍曼不动杆菌对大部分抗菌药物的耐药率有差异(P<0.05),保持较高的耐药水平。所以加强本单位的细菌耐药监测工作,对指导临床医生合理应用抗菌药物,减少和延缓耐药菌株的出现,有效控制医院内感染意义深远。更多还原

【Abstract】 In early 1928, Penicillin was discovered by the British medical scientist Fleming,Since then, the infectious diseases without antimicrobial treatment era ended forever.With the development of the times,various antimicrobial were rapidly developed and widely used in various types of infectious diseases treatment, and played a positive role, which effectively controled the diseases, prolonged the life of patients and improved the quality of life of patients.However, bacterial resistance brings a new difficult problem to clinical treatment. Especially gram-negative bacillus drug resistance problem has become a concern of the whole society as a public health problem..At present, the whole world is carrying out a variety of sizes of the bacterial resistance surveillance work. For example, the United States is to establish a national nosocomial infection surveillance system ( NNIS ), the world more than 30 countries involved in the SENTRY antibacterial drug monitoring project, Europe has established the European bacterial resistance surveillance system ( EARSS ), etc.. China has also done a variety of sizes of the bacterial resistance surveillance work, such as the national antimicrobial resistance monitoring network ( Mohnarin ), the bacterial isolates resistant to Etest and agar dilution method in monitoring ( SEANIR ), Chinese CHINET bacterial resistance monitoring etc..Due to that application of antimicrobial agents have different habits in the different areas,the bacterial resistance and development are also different. The data shows that in different countries, different regions, different hospitals, the different sections of the same hospital, the bacterial drug resistance rates also were different. Therefore, understanding of bacterial distribution and drug resistance monitoring results guides clinicians in our region and units to correctly use antimicrobial drugs,which is very important to reduce and delay the emergence of resistant strains and effectively control the prevalence of resistant strains. Understanding the distribution and resistance situation of clinical isolates of gram-negative bacilli in our hospital from2009 to 2010, provides the basis for clinical rationally use of antimicrobial agents, and this study collected 1171 clinical isolates of gram-negative bacilli from 2009 January to 2010 December ( excluding separations of the repeated strain from the same patient or the same parts ). The use of French bioMerieux API identification system and Vitek-compact identification system for bacteria identification was made. Drug sensitivity test used disc diffusion method (Kirby-bauer method) according to CLSI M100 rules as the standard interpretation of results.The statistical results were analyzed by WHONET5.3 software and SPSS13.0 statistical software.The results showed that 1171 isolates of gram-negative bacilli were separated from January 2009 to December 2010, of which 689 strains were separated in 2009 and the top five of the pathogenic bacteria were Klebsiella, Acinetobacter Baumannii, Pseudomonas aeruginosa, Enterobacter cloacae, Escherichia coli; and 482 strains of the Gram-negative bacteria were separated in 2010 and the top five of the pathogenic bacteria were Klebsiella, Acinetobacter Baumannii, Pseudomonas aeruginosa, Escherichia coli, Stenotrophomonas maltophilia. The main departments that pathogenic bacteria come from were respiratory medical department and ICU,and the main source of the pathogen specimen were sputum specimens. In addition to Klebsiella, Serratia, Acinetobacter Baumannii, Pseudomonas aeruginosa on the part of antimicrobial drug resistance rate were different (P < 0.05 ) between 2009 and 2010, but other gram-negative bacilli on antimicrobial resistance rates did not have obvious difference (P > 0.05 ) in 2009 and 2010. For Enterobacteriaceae, only Piperacillin / Tazobactam, Cefoperazone / Sulbactam, Imipenem, Meraopenem had maintained good antibacterial activity, but there are also some resistance, and resistance rates were from 0.0% to 17.0%.For other beta-lactam antibiotics had very high resistance rate,which might be related to the generation of Carbapenemase, Ampc metal enzyme, Extended-spectrum-β-lactamases . Escherichia coli on ciprofloxacin resistance rate is greater than 73.6%, and other Enterobacteriaceae on ciprofloxacin resistance rates were mostly from 15.0% to 23.0%. For Enterobacteriaceae, The resistance rates of Amikacin was significantly lower than those of gentamicin, which might be associated with the Amikacin rare clinical application and it had strong tolerance to enzyme. For Nonfermentative gram-negative bacilli, multiple drug resistance situation of Acinetobacter Baumannii were serious, besides the resistance rates of Cefoperazone / Sulbactam had difference (P< 0.05 ) in 2009 and 2010 ,and the resistance rates of other antimicrobial agent had not obvious difference.And only the Cefoperazone / Sulbactam has good antibacterial activity. In 2009, 17 strains of Pan resistant strains were detected, and 24 strains of Pan resistant strains were detected in 2010. Cause of serious resistance phenomenon might be related to the generation of Extended-spectrum-β-lactamases, Ampc enzyme, Carbapenemase and otherβ-lactamases, and aminoglycoside inactivating enzymes, gyrA /parC gene mutation and so on.Antimicrobial resistance rates of Pseudomonas aeruginosa and Stenotrophomonas maltophilia were much lower than 20%. The reason for this phenomenon was that probably medication starting point was low in our hospital or rotation dosing strategies were used well by doctors or originated from the colonization of bacteria and so on. For Enterobacteriaceae of ICU and non-ICU, , only the resistance rate of Enterobacter cloacae to ticarcillin / clavulanate had difference (P<0.05 ) in 2009 and 2010. In addition to Enterobacter cloacae, antibacterial activity of imipenem and meropenem was the strongest on other Enterobacteriaceae, followed by piperacillin / tazobactam, Cefoperazone / Sulbactam, Amikacin, and antibacterial activity of ampicillin was the worst. For non-fermenting Gram-negative bacteria from ICU and non-ICU ,the resistance rate of Acinetobacter baumannii from ICU to most antibiotics was significantly higher than that from non-ICU, and the resistance rates of Acinetobacter baumannii to most antimicrobial agents had differences between them (P<0.05). The antibacterial activity of Cefoperazone / Sulbactam is only the best to Acinetobacter baumannii, and the antibacterial activity of other antimicrobial agents to Acinetobacter baumannii remained higher resistant state. The reason for this situation is that patients in the ICU have common characteristics ,such as endotracheal intubation, tracheotomy , use of ventilator with a long hospital stay, serious underlying diseases, long-term application of broad-spectrum antibiotics and so on.This study shows that antimicrobia resistance of Gram-negative bacilli in our hospital is very serious.Only several antibiotics had good antibacterial activity,such as Piperacillin / Tazobactam, Cefoperazone / Sulbactam, Imipenem, Meropenem, Amikacin and so on. Most antimicrobial resistance rates to Acinetobacter baumannii were different (P<0.05) between the ICU and the non-ICUand remainded a high level of resistance. So Bacterial resistance surveillance works should have been finished well, which has far-reaching significance for guiding the rational use of antimicrobial drugs, reducing and delaying the emergence of resistant strains and effectively controlling nosocomial infections.更多还原