淋球菌对头孢菌素类等药物的敏感性与MLVA分型研究及其联合作用的研究

发布时间：2018-04-09 17:29

本文选题：淋球菌　切入点：Meta分析　出处：《北京协和医学院》2015年博士论文

【摘要】：第一部分：淋球菌对头孢克肟及阿奇霉素敏感性Meta分析研究[目的]分析世界范围内淋球菌对头孢克肟和头孢泊肟的敏感性及相关因素；分析中国地区淋球菌对阿奇霉素敏感性及相关因素。[方法] 两位研究者分别对PubMed. Embase、Web of Science、CNKI和万方数据库独立检索已经发表的文献,共有21篇有关头孢克肟敏感性文献和5篇有关头孢泊肟敏感性文献纳入Meta分析,共有8篇有关淋球菌对阿奇霉素敏感性文献纳入Meta分析,亚组分析应用卡方检验。[结果]经Meta分析后,淋球菌对头孢克肟的敏感性检测率为99.8%(95%CI：99.7%-99.8%)。亚组分析发现,收集于男性患者的淋球菌对头孢克肟的敏感性检测率比来自于无性别信息患者(96.5% vs.99.9%,χ2=1341.499, P0.001)或者男性和女性患者高(96.5% vs.99.8%, χ2=6776.778, P0.001)。亚洲地区淋球菌对头孢克肟的敏感性检测率低于欧洲(97.4% vs.99.0%, χ2=669.637, p0.001)、北美洲(97.4%vs.99.9%, x2=183.740, P0.001)和非洲(97.4% vs.99.5%, χ2=3.987, P=0.046)。2003年前淋球菌对头孢克肟的敏感性检测率比2003年后高(99.8% vs.99.0%, χ2=198.597,P0.001)。经Meta分析后,淋球菌对头孢泊肟的敏感性检测率为92.8%(95CI：89.0%-95.3%),并且比头孢克肟的敏感性检测率低(92.8% vs.99.8%, χ2=951.809, P0.001)。经Meta分析后,淋球菌对阿奇霉素的耐药率为6.3%(95%CI 3.3-11.6%).亚组分析发现,在2008年前收集的淋球菌对阿奇霉素的耐药率比2008年及以后收集的淋球菌对阿奇霉素的耐药率低(2.0% vs.12.5%, χ2=27.650, P0.001)。广东地区淋球菌对阿奇霉素的耐药率最高,其次为南京、重庆地区,最低为山东河北地区(χ2=22.321,P0.001)。[结论]在世界范围内,总体来讲淋球菌对头孢克肟敏感,但淋球菌对头孢克肟的敏感性在不同性别、不同地区存在差异,并且随着时间的变化逐渐降低,且淋球菌对头孢泊肟敏感性较头孢克肟低。在中国地区淋球菌对阿奇霉素的敏感性有地区差异,特别是广东省,阿奇霉素不宜单独作为治疗淋病的一线用药。第二部分：淋球菌对头孢克肟及其他抗生素的敏感性及MLVA分型研究[目的]了解中国地区淋球菌临床分离菌株对头孢克肟及其他抗生素的敏感性及获取多位点串联重复序列分型(Multiple-locus variable number tandem repeat ananlysis, MLVA)生物学信息。[方法]2012年在广州、南京和天津地区性病门诊收集244株淋球菌临床分离菌株,检测其对青霉素、四环素、环丙沙星、壮观霉素、头孢曲松和头孢克肟的敏感性。应用MLVA分型方法对244株淋球菌临床分离菌株进行基因分型。[结果]在广州、南京和天津三个城市中,质粒介导高度耐四环素淋球菌(Plasmid-mediated high level tetracycline-resistant Neisseria gonorrhoeae,TRNG) (χ2=26.418,P0.001)、头孢曲松低敏菌株(χ2=4.417,P=0.093)、头孢曲松低敏且头孢克肟非敏感菌株(χ2=2.768,P=0.096)检测率差异有统计学意义。头孢曲松低敏菌株与广州(odds ratio 14.428,95%CI 3.194-65.169, P=0.001)、南京(odds ratio 6.959,95%CI 1.532-31.616, P=0.012)和头孢克肟低敏菌株(odds ratio 2.378,95%CI1.103-5.310,P=0.027)正相关。头孢克肟非敏感菌株与产青霉素酶淋球菌(Penicillinase-producing Neisseria gonorrhoeae,PPNG) (odds ratio 0.537, 95%CI0.267-1.080,P=0.081)、TRNG (odds ratio 0.472,95%CI 0.232-0.964, P=0.039)负相关,与头孢曲松非敏感菌株(odds ratio 2.017,95%CI 0.957-4.249, P=0.065)正相关。244株淋球菌临床分离菌株进行MLVA分型,共获取110种基因型别和5个簇,其中簇Ⅲ与PPNG菌株相关(P=0.008),簇Ⅱ与非PPNG (P=0.008)及头孢曲松低敏菌株相关(P=0.024)。[结论]在中国广州、南京和天津地区可用头孢曲松和壮观霉素治疗淋病,但青霉素、四环素和环丙沙星和头孢克肟不适合用来推荐治疗淋病。MLVA分型可用于淋球菌基因分型,并且淋球菌对抗生素的敏感性可能与某些簇相关。第三部分：头孢曲松和阿奇霉素在体外抗淋球菌联合作用的研究[目的]研究头孢曲松和阿奇霉素在体外抗淋球菌的联合作用。[方法]2012年在大连地区性病门诊共收集25株淋球菌临床分离菌株,用Etest法检测头孢曲松和阿奇霉素在体外抗淋球菌的联合作用,计算部分抑菌浓度指数(Fractional inhibitory concentration index, FICI)判断头孢曲松和阿奇霉素在体外抗淋球菌的联合作用。[结果]共检测25株大连地区收集的淋球菌临床分离菌株,FICI在0.724-2.696之间,头孢曲松和阿奇霉素对所有淋球菌临床分离菌株都有相加作用,无协同作用,但也无拮抗作用。[结论]头孢曲松和阿奇霉素联合使用治疗淋病可能是未来中国推荐指南的一个选择。
[Abstract]:The first part: Neisseria gonorrhoeae to cefixime and azithromycin sensitivity of Meta analysis to analyze the sensitivity of the world within the scope of Neisseria gonorrhoeae to cefixime and cefpodoxime and related factors analysis; China of Neisseria gonorrhoeae in azithromycin sensitivity and related factors. Methods: two researchers respectively on PubMed. Embase, Web of Science the independent, published literature retrieval of CNKI and Wanfang database, a total of 21 articles on cefixime sensitivity and 5 articles about cefpodoxime susceptibility literature into Meta analysis, a total of 8 papers of Neisseria gonorrhoeae to azithromycin sensitive documents into Meta analysis, subgroup analysis by chi square test. Results: after after Meta analysis, Neisseria gonorrhoeae susceptibility test of cefixime in rate was 99.8% (95%CI:99.7%-99.8%). Subgroup analysis found that the sensitivity of detection of Neisseria gonorrhoeae collected in male patients of cefixime Detection rate than those from the non gender information of patients (96.5% vs.99.9%, X 2=1341.499, P0.001) or men and women with high (96.5% vs.99.8% x 2=6776.778, P0.001). The sensitivity of detection of Neisseria gonorrhoeae in Asia cefixime was lower than in Europe (97.4% vs.99.0%, 669.637 x 2=, p0.001), North America (97.4%vs.99.9% x2=183.740, P0.001) and Africa (97.4% x 2=3.987, vs.99.5%, P=0.046).2003 years ago gonococcal susceptibility test of cefixime in high rate than in 2003 (99.8% vs.99.0%, X 2=198.597, P0.001). By Meta analysis, the sensitivity of detection of Neisseria gonorrhoeae Cefodoxime rate was 92.8% (95CI:89.0%-95.3%). And the ratio of sensitivity of cefixime low rate (92.8% vs.99.8%, X 2=951.809, P0.001). Through Meta analysis, gonococcal resistance to azithromycin was 6.3% (95%CI 3.3-11.6%). Subgroup analysis found that gonococcus collected in 2008 before Gonococcal bacteria resistance to azithromycin ratio after 2008 and collected the low rate of resistance to azithromycin (2% x 2=27.650, vs.12.5%, P0.001). Drug resistance of Neisseria gonorrhoeae in Guangdong area of azithromycin was the highest, followed by Nanjing, Chongqing, the lowest in Shandong Hebei area (x 2=22.321, P0.001)] in conclusion. In the world, the whole of Neisseria gonorrhoeae to cefixime sensitive, but the sensitivity of Neisseria gonorrhoeae to cefixime in different gender, different regions, and with the change of time decreased gradually, and the gonococcus to cefpodoxime sensitivity is low. In Chinese cefixime Neisseria gonorrhoeae has regional differences of sensitivity azithromycin, especially in Guangdong Province, should not be alone as first-line therapy of azithromycin in the treatment of gonorrhea. The second part: the sensitivity and MLVA of Neisseria gonorrhoeae to cefixime and other antibiotic type [Objective] To understand the sensitivity of China Neisseria gonorrhoeae in clinical isolates of cefixime and other antibiotics and obtain multilocus tandem repeat typing (Multiple-locus variable number tandem repeat ananlysis, MLVA]2012) method. The biological information in Guangzhou, Nanjing and Tianjin area were collected from 244 STD clinic strains of Neisseria gonorrhoeae in clinical isolates, the detection of penicillin, tetracycline, ciprofloxacin, spectinomycin, sensitivity to ceftriaxone and cefixime. Application of MLVA genotyping method of 244 strains of Neisseria gonorrhoeae isolates were genotyped. Results: in Guangzhou, Nanjing and Tianjin city in three, the height of the plasmid mediated tetracycline resistant Neisseria gonorrhoeae (Plasmid-mediated high level tetracycline-resistant Neisseria gonorrhoeae TRNG (x), 2=26.418, P0.001), ceftriaxone low sensitive strains (x 2=4.417, P=0.093), head of ceftriaxone and cefixime in low sensitivity Non sensitive isolates (2=2.768, P=0.096) detection rate was statistically significant. Reduced susceptibility to ceftriaxone isolates from Guangzhou (odds ratio 14.428,95%CI 3.194-65.169, P=0.001), Nanjing (odds ratio 6.959,95%CI 1.532-31.616, P=0.012) and cefixime (odds ratio low sensitive strains 2.378,95%CI1.103-5.310, P=0.027) is related to cefixime non sensitive strains. With penicillinase producing Neisseria gonorrhoeae (Penicillinase-producing Neisseria gonorrhoeae PPNG (odds) ratio 0.537, 95%CI0.267-1.080, P=0.081), TRNG (odds ratio 0.472,95%CI 0.232-0.964, P=0.039) negative correlation with ceftriaxone non sensitive strain (odds ratio 2.017,95%CI 0.957-4.249, P=0.065) is related to.244 clinical strains of Neisseria gonorrhoeae strains were classified with MLVA and CO to obtain 110 genotypes and 5 clusters, the cluster III associated with strain PPNG (P =0.008), cluster II and non PPNG (P=0.008) and ceftriaxone Low sensitive strain related (P=0.024). Conclusion] in Guangzhou Chinese, Nanjing and Tianjin area available for ceftriaxone and spectinomycin in treatment of gonorrhea, but penicillin, tetracycline and ciprofloxacin and cefixime is not suitable for the recommended treatment of gonorrhea.MLVA type can be used for the genotyping of Neisseria gonorrhoeae, and susceptibility of Neisseria gonorrhoeae to antibiotics may be related and some of the cluster. The third part: the combination of]2012 method. Effect of combined effects of ceftriaxone and azithromycin in vitro against Neisseria gonorrhoeae research [Objective] of ceftriaxone and azithromycin in vitro against Neisseria gonorrhoeae in Dalian area of STD clinic were collected from 25 strains of Neisseria gonorrhoeae isolates, the combined effect of ceftriaxone and detected by Etest azithromycin in vitro against Neisseria gonorrhoeae, calculating the fractional inhibitory concentration index (Fractional inhibitory concentration index, FICI) to determine ceftriaxone and spectinomycin. The combined effects of in vitro. Anti gonococcus were detected in 25 strains of Neisseria gonorrhoeae in Dalian collected clinical isolates, FICI between 0.724-2.696, ceftriaxone and azithromycin have additive effect on all clinical isolates of Neisseria gonorrhoeae, no synergistic effect, but also no antagonistic effect. Conclusion ceftriaxone and Azithromycin combined with the use of the treatment of gonorrhea may be a choice for the future China recommendations.

【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R759.2

【参考文献】