鲍曼不动杆菌临床感染菌株的药敏分析及对替加环素耐药机制的初探

发布时间：2018-10-16 09:52

【摘要】：目的:了解我院242株临床分离鲍曼不动杆菌感染患者的临床特征,检测其对常见抗菌药物敏感性,检测外排泵基因分布及部分外排泵基因表达水平,初探鲍曼不动杆菌耐替加环素的机制。方法:收集川北医学院附属医院2015年9月至2016年9月培养到的鲍曼不动杆菌株和相关临床资料,用K-B法对其进行体外药敏试验,并用PCR方法对adeB,adeG,adeJ,adeR,ade S,adeE,abeM,tetA,tetB,abeS等外排泵基因进行检测,对同时检出adeB,adeG,adeJ,abeM的菌株根据药敏试验分为对替加环素敏感组和耐药组,利用qPCR方法检测ade B,adeG,adeJ,abeM表达量并进行比较。结果:1.242株临床分离鲍曼不动杆菌标本来源于痰液最多,达181株(占74.79%),其次是脓液41株(16.94%)。科室分布前三位分别为:ICU(45.04%),神经外科(19.01%)和呼吸内科(18.18%)。显示男性138例,女性104例;≥70岁的有157例,50~70岁的64例;合并颅脑疾病最多,有65例(26.86%),合并COPD、糖尿病、心血管疾病分别有56例(23.14%)、46例(19.00%)、42例(17.36%)。合并器官衰竭情况:呼吸衰竭101例(41.73%),心功能衰竭39例(16.11%),肾功能衰竭15例(6.20%);抗菌药物使用情况:II联用药147例(60.74%),I联用药62例(25.62%),III联及以上用药33例(13.64%);住院期间使用过3种及以上抗菌药物的有149例(61.57%),使用过碳青霉烯类类抗生素的有87例(35.95%);有侵袭性操作者占86.78%;人工气道或机械通气者占62%;预后:住院期间无明显好转或死亡的有92例(38.02%);平均住院天数46.2天。2.我院临床分离的242株鲍曼不动杆菌体外药敏试验显示:鲍曼不动杆菌对头孢哌酮-舒巴坦、美罗培南、亚胺培南、替加环素耐药率50%,分别为45.04%、29.75%、27.27%、3.31%;对头孢吡肟、头孢曲松、头孢噻肟、头孢他啶耐药率分别为75.21%、73.55%、71.07%、66.53%;对链霉素、庆大霉素、氨苄西林/舒巴坦、哌拉西林/他唑巴坦、环丙沙星、左氧氟沙星、阿米卡星耐药率分别为:87.60%、83.06%、78.10%、77.69%、77.69%、66.12%、65.29%。3.我院242株鲍曼不动杆菌外排泵基因adeb,adeg,adej,ader,ades,adee,abem,teta,tetb,abes检出率分别为:81.82%、85.95%、83.47%、81.00%、78.93%、0%、80.58%、21.49%、46.28%、100%。对同时检测到adeb、adeg、adej、abem基因的菌株以对替加环素耐药与否分为敏感组和耐药组,检测其adeb、adeg、adej、abem的表达量,并对其进行比较,结果显示:adeb、adeg、adej、abem的表达量在耐药组:敏感组分别为:21倍、1倍、5倍、1倍。结论:1.我院鲍曼不动杆菌菌株分布主要在icu,其次是神经外科、呼吸内科,主要来源于痰液,感染患者年龄偏大,大部分在70岁以上,合并基础疾病多且病情重,住院期间抗菌药物使用种类多,联用现象常见,以肺部感染居多,容易发生呼吸衰竭,侵袭性操作或手术可能为鲍曼不动杆菌感染的危险因素。2.我院临床分离鲍曼不动杆菌对头孢吡肟、头孢曲松、头孢噻肟、头孢他啶耐药率高,对头孢哌酮-舒巴坦耐药率高于美罗培南、亚胺培南等碳青霉烯类抗菌药物,对替加环素耐药率低,碳青霉烯类抗菌药物、替加环素可以作为我院临床治疗鲍曼不动杆菌感染的首选药物。3.此次试验鲍曼不动杆菌中RND(adeABC、adeFGH、adeIJK)外排泵基因检出率普遍高,耐药组检出率高于敏感组,故鲍曼不动杆菌对抗菌药物的耐药可能主要由RND外排泵介导有关;adeE检出率为0,证明我院鲍曼不动杆菌可能不存在adeE外排泵基因流行现象。4.外排泵adeABC、adeIJK的高表达介导我院鲍曼不动杆菌对替加环素耐药,而RND外排泵家族中的adeFGH和abeM(即MATE外排泵系统)是否介导我院鲍曼不动杆菌对替加环素耐药需扩大样本进一步研究。
[Abstract]:Objective: To investigate the clinical characteristics of 242 clinical isolates of Baumannii infection in our hospital, to detect the susceptibility to common antimicrobial agents, to detect the distribution of efflux pump gene and the expression level of partial efflux pump gene. Methods: The drug sensitivity test was carried out in vitro by K-B method, and adeB, deG, adej, adeR, ade S, adeE, abeM, teA and teB were collected by using K-B method. The strains of adeB, adeG, adeJ and abeM were divided into sensitive groups and drug resistant groups according to the susceptibility test, and the expression levels of ade B, adeG, adej and abeM were detected by qPCR method and compared. Results: There were 181 strains (74. 79%) and 41 strains of pus (16.94%). The first three sections were ICU (45. 04%), neurosurgery (19. 01%) and respiratory medicine (18. 18%). There were 138 males, 104 females, 157 females aged 50 to 70 years old, and 64 patients aged 50 to 70 years old; 56 (23.14%), 46 (19. 00%), 42 (17. 36%) were combined with COPD, diabetes and cardiovascular diseases. The condition of organ failure: 101 cases of respiratory failure (41. 73%), 39 cases of cardiac failure (16. 11%), 15 cases of renal failure (6. 20%), and the use of antibacterial drugs: 147 cases (60. 74%), 62 cases (25.62%) of I-linked drugs, and 33 cases (13.64%) of drug use. There were 149 cases (61. 57%) of the antibacterial drugs used during hospitalization, 87 (35. 95%) were used for carbapillenems, 86. 78% were invasive operators, 62% were artificial airway or mechanical ventilation, and the prognosis was as follows: There were 92 patients (38. 02%) who had no improvement or death during hospitalization; the average length of hospital stay was 46. 2 days. In vitro chemosensitivity test of 242 strains of Baumannii isolated from our hospital showed that the drug resistance rate was 50%, 45.04%, 29.75%, 27.27% and 3.31%, respectively. The resistance rates of ceftaxime and methamidophos were 75. 21%, 73. 55%, 71. 07%, 66. 53%, respectively. 77. 69%, 66. 12%, 65. 29%. 3. The positive rates of adeb, adeg, adej, ader, ades, adee, abem, taeta, teb, abes of 242 strains of Baumannii in our hospital were 81 82%, 85 95%, 83 47%, 81. 00%, 78. 93%, 0%, 80. 58%, 21.49%, 46. 28% and 100% respectively. The expression of adeb, adeg, adej and abem was detected by adeb, adeg, adej and abem genes, and the expression of adeb, adeg, adej and abem was tested, and the results showed that adeb, adeg, adej, abem were expressed in drug resistant group: The sensitivity groups were 21 times, 1-fold, 5-fold and 1-fold, respectively. Conclusion: 1. The distribution of the strains of Baumannii in our hospital is mainly in icu, followed by neurosurgery and respiratory medicine, mainly from sputum, the age of infected patients is large, most of them are over 70 years old, and the combination of basic diseases is more and more serious. The use of antibacterial drugs during hospitalization is much more common, and the combination phenomenon is common. In most cases of pulmonary infection, respiratory failure, invasive operation or operation may be a risk factor for the infection of Bowman. The drug resistance rate of ceftaxime, ceftripine, cefixime and drug resistance was high in the clinical isolates of Baumannii in our hospital. Carbapenem antibacterial drugs, tigecycline can be used as the first choice medicine for the clinical treatment of Baumannii infection in our hospital. The detection rate of RND (deABC, adeFGH, adeIIEF) efflux pump was generally high in Baumannii, and the detection rate of drug-resistant group was higher than that in the sensitive group. Therefore, the drug resistance of B. baumannii to antibacterial drugs could be mainly mediated by RND efflux pump, and the detection rate of adeE was 0. It is proved that there may not be adee efflux pump gene epidemic phenomenon in Baumannii in our hospital. The high expression of deABC and adeIIIa of efflux pump mediated the drug resistance of Baumannii in our hospital, while adeFGH and abeM (i.e. MATE efflux pump system) in the RAND efflux pump family mediate the further study of the drug resistance of Baumannii in our hospital.
【学位授予单位】：川北医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R446.5

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