摘要
目的
调查研究2008年1月～2009年12月天津医科大学总医院急救中心病房危重症患者病原菌耐药趋势,为临床合理使用抗生素提供依据。
方法
对2008年1月～2009年12月在急救中心病房危重症患者送检的临床各类标本中分离的病原菌,描述其在2年间的分布情况,调查2年间临床常见的病原菌对常用抗生素的药敏结果,探讨临床常见的病原菌的耐药与变迁。标本按《全国临床检验操作规程》培养分离菌株,并用法国生物梅里埃公司生产的VITEK-AMS全自动微生物分析仪测定病原菌,采用Kirby-Bauer纸片扩散法(K-B)法进行抗生素敏感试验。使用纸片初筛选法和纸片表型确证试验检测产超广谱β-内酰胺酶的菌株。按美国临床实验室标本委员会(NCCLs)判断标准进行药敏试验结果判断。用SPSS17.0统计软件建立数据库并进行统计学分析,统计学方法包括一般描述性方法,比较产ESBLs组和非产ESBLs组的耐药率,用K-S法检验数据资料,显示数据呈正态分布,用Logistic进行多重耐药菌危险因素分析,以p<0.05为有统计学意义。
结果
1.本次调查2年间共分离出病原菌738株,其中革兰阴性杆菌442株,占总分离数的59.9%；革兰阳性菌96株,占13.0%；真菌200株,占27.1%。在革兰阴性菌位居前五位的依次为铜绿假单胞菌116株,占26.2%；肺炎克雷伯菌84株,占19.0%；大肠埃希菌59株,占13.3%；鲍曼不动杆菌54株,占12.2%；阴沟肠杆菌30株,占6.8%。革兰阳性菌中主要菌株为肠球菌42株,占43.8%；葡萄球菌41株,占42.7%；其中耐甲氧西林的葡萄球菌25株,占61.0%；耐高浓度氨基糖苷类肠球菌33株,占78.6%。未发现耐万古霉素的革兰阳性菌。真菌中以白色假丝酵母菌为主,占真菌分离数的80.0%。
2.临床分离的病原菌主要来自于呼吸道痰标本,占总分离菌的77.0%,其次是泌尿道,占18.2%,血标本只占2.4%。
3.耐药结果分析显示：五种常见革兰阴性杆菌对临床常用抗生素总体耐药率最低的是美罗培南5.9%,亚胺培南的耐药率为13.4%,氨苄西林耐药率最高,为93.7%。铜绿假单胞菌对美罗培南和亚胺培南的敏感率最高,分别为87.0%和70.0%,对头孢噻吩和头孢唑林的耐药率均为100%。肺炎克雷伯菌对亚胺培南和美罗培南的敏感率最高,分别为96.4%和98.8%,对氨苄西林的耐药率最高,耐药率为100%。大肠埃希菌对抗菌药物敏感率最高的是亚胺培南和美罗培南及青霉素类的哌拉西林/他唑巴坦敏感率较高分别为98.3%、96.7%和98.3%,头孢哌酮舒巴坦、头孢西丁的敏感率为86.4%和83.1%,丁胺卡那霉素的敏感率为82.1%,其余药物敏感率均低于60%。鲍曼不动杆菌对亚胺培南和美罗培南的敏感率最高,均达到了100%,对头孢哌酮/舒巴坦、头孢他啶、头孢吡肟、替卡西林/棒酸的敏感率均在90%以上,头孢噻肟、替卡西林、哌拉西林/他唑巴坦、庆大霉素、丁胺卡那霉素、妥布霉素、奈替米星、左旋氧氟沙星、复方新诺明的敏感率均大于80%,呋喃妥因耐药率为100%。阴沟肠杆菌对多数抗菌药物均有较好的活性,敏感率最高的是亚胺培南和美罗培南以及奈替米星,敏感率均为100%,丁胺卡那霉素、妥布霉素的敏感率均在90%以上
4.实验共分离出产超广谱β-内酰胺酶的菌株51株,检出率为11.5%,其中产ESBLs的肺炎克雷伯菌23株,产酶率为27.4%,产ESBLs的大肠埃希菌是28株,产酶率为47.5%。肺炎克雷伯菌和大肠埃希菌是产超广谱β-内酰胺酶的主要菌株。肺炎克雷伯菌和大肠埃希菌的产ESBLs菌株的耐药率明显高于非产ESBLs组。
5.葡萄球菌对抗生素敏感率最高的是呋喃妥因和万古霉素,敏感率均为100%,其次是利奈唑烷,敏感率为94.6%。肠球菌对抗菌药物敏感率最高的是利奈唑烷和万古霉素,敏感率为95.2%和100%,未发现对万古霉素耐药的菌株。
6.真菌抗菌活性最好的是5-氟胞嘧啶,敏感率为100%、其次为两性霉素B、酮康唑敏感率均达99.0%,特比萘芬、制霉菌素耐药率最高均达80.0%以上。
结论
1.呼吸道是危重症患者院内感染主要部位,主要与患者高龄、合并肺部疾病多、长期卧床,营养状态差,气管插管、呼吸机使用以及既往应用广谱抗菌药物导致呼吸道二重感染有关。
2.革兰阴性菌是危重症患者院内感染主要致病菌,其中铜绿假单胞菌、肺炎克雷伯菌、大肠埃希菌、鲍曼不动杆菌、阴沟肠杆菌最常见。真菌成为第二大感染菌,主要与有创检查,免疫抑制剂、以及抗菌药物的不合理应用有关。多重耐药菌株主要为铜绿假单胞菌,侵入性操作、抗生素使用是多重耐药菌株铜绿假单胞菌的独立危险因素。
3.革兰阴性杆菌对青霉素和一、二代头孢菌素耐药率较高,耐药率达50%以上,对三、四代头孢菌素有较好的敏感性,敏感率在50%以上。革兰阴性杆菌对亚胺培南和美罗培南最敏感,敏感率在95%以上,但铜绿假单胞菌对其的敏感性在70%以上。革兰阳性球菌对红霉素、青霉素有较高的耐药率,耐药率达80%以上,对万古霉素、利奈唑烷最敏感,敏感率在94%以上。真菌对两性霉素B、5-氟胞嘧啶、氟康唑和酮康唑敏感率在96%以上,特比萘芬和制霉菌素的敏感率较低,敏感率在10%以下。
4.监测细菌耐药性的变化,依据药物敏感试验结果合理的选用抗生素,及时调整经验性用药是至关重要的。
Objectives To investigate the distribution and antimicrobial resistance trend of pathogens in patients from Emergency Intensive Care Unit(ICU)of Tianjin Medical University between July 2008 and Dec 2009, so as to provide theoretical bases of rational usage of antibiotics and experienced therapy for the clinic.
Methods Distribution of the main pathogens isolated from all specimens of critical patients and antimicrobial susceptibility test results were analyzed retrospectively. Flora cultivation and isolation was operated with the methods described by the National Clinical Laboratory Operational Regulations.Bacterial identification was carried out using VITEK-AMS.Bacterial susceptibility testing was carried out using Kirby-bauey methods. Two kinds of disc diffusion sorcening test and phenotypic confirmatory test were used to detect Extended-Spectrumβ-Lactamases(ESBLs) in bacteria;The resistant rate of bacteria was analyzed according to the guidelines of the National Committee for Clinical Laboratory Standards. Data were analyzed with SPSS 17.0 software and ststistical methods including general descriptive methods, Compare the resistance rate in ESBLs-produced group and in non-ESBLs-produced group, then the data were tested by K-S method, which was shown to be in normal distribution.
Results 1.738 strains of pathogenic bacteria were isolated from clinical samples during 2 years,among which there are 442 strains of Gram-negative bacilli among them,accounting for 59.5% in total clinical isolates; 96 strains of Gram-positive bacteria among them, accounting for 13.0% in total clinical isolates; 200 strains of fungus among them, accounting for 27.1% in total clinical isolates. The common Gram-negative bacilli were mainly Pseudomonas aeruginosa 116 strains(26.2%), Klebsiella spp 84 strains(19.0%), Escherichia coli 59 strains(13.3%),Acinetobacter baumannii 54 strains(12.2%), Enterobacter cloacae 30 strains(6.8%), The common Gram-positive bacilli were Enterococcus42strains(43.8%), Staphylococcus41 strains(42.7%). Methicillin resistant Staphylococcus accountde for 61.0% in total Staphylococcus. High concentration of Aminoglycoside resistant enterococci accounted for 78.6% in the total Enterococcus. No vancomycin-resistant gram-positive bacteria was found. The common fungus was Candida albicans, accounting for 80.0% in total clinical fungus isolates.2.77.0% pathogens are isolated from specimens in respiratory tract and 18.2% from than in urinary tract among 738 strains of pathogens, blood specimens only account for 2.4%.3. According to surveillance of drug resistance, the clinical antibacterial drugs with the lowest total drug-resistant rates of Gram-negative bacilli were imipenem and meropem.4. A total of 51 strains of ESBLs-produced bacteria were isolated, the detecting rate is 11.5%. They include 23 strains of Klebsiella pneumonia whose ESBLs-produced rate is 27.4% and 28 strains of Escherichia coli whose ESBLs-produced rate is 47.5%. Klebsiella pneumonia and Escherichia coli were predominant strains of ESBLs-producing. The resistance rates of ESBLs-produced strains to the common antimicrobial agents were Significantly higher than those of non-ESBLs-producing strains.5. Vancomycing and Nitrofurantoin are the most effective antibiotics against staphylococcus and enterococci.No vancomycin-resistant strains were detected.6. 5-flurocytosine Amphotericin B and Ketoconazole Capsules were the most active antibiotic against fungus.
Conclusions 1. Respiratory tract is the main site where nosocomial infections occur in critically ill patients.2. Gram-negative bacterium is the main pathogenic bacteria in nosocomial infection, Invasive procedures and antibiotic use are independent risk factors of the multi-drug resistant strains of Pseudomonas aeruginosa.3. Third and fourth generation cephalosporins against gram-negative bacteria has good sensitivity, and the sensitivity ratio is over 50%. Imipenem and Meropenem against Gram-negative bacteria are most sensitive, and the sensitivity ratio is more than 95%. Vancomycin, linezolid against gram-positive bacteria are most sensitive, and the sensitivity ratio is above 94%. Amphotericin B,5 - fluorocytosine, fluconazole and ketoconazole have good sensitivity against fungal, and the sensitivity ratio is above 96%.4. Monitoring bacteria resistant, according to antimicrobial susceptibility test changes result chosing antibiotic adjust experience administration is very important.
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