本文選題：淋球菌　切入點(diǎn)：Meta分析　出處：《北京協(xié)和醫(yī)學(xué)院》2015年博士論文

【摘要】：第一部分：淋球菌對頭孢克肟及阿奇霉素敏感性Meta分析研究[目的]分析世界范圍內(nèi)淋球菌對頭孢克肟和頭孢泊肟的敏感性及相關(guān)因素；分析中國地區(qū)淋球菌對阿奇霉素敏感性及相關(guān)因素。[方法] 兩位研究者分別對PubMed. Embase、Web of Science、CNKI和萬方數(shù)據(jù)庫獨(dú)立檢索已經(jīng)發(fā)表的文獻(xiàn),共有21篇有關(guān)頭孢克肟敏感性文獻(xiàn)和5篇有關(guān)頭孢泊肟敏感性文獻(xiàn)納入Meta分析,共有8篇有關(guān)淋球菌對阿奇霉素敏感性文獻(xiàn)納入Meta分析,亞組分析應(yīng)用卡方檢驗(yàn)。[結(jié)果]經(jīng)Meta分析后,淋球菌對頭孢克肟的敏感性檢測率為99.8%(95%CI：99.7%-99.8%)。亞組分析發(fā)現(xiàn),收集于男性患者的淋球菌對頭孢克肟的敏感性檢測率比來自于無性別信息患者(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)。亞洲地區(qū)淋球菌對頭孢克肟的敏感性檢測率低于歐洲(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年前淋球菌對頭孢克肟的敏感性檢測率比2003年后高(99.8% vs.99.0%, χ2=198.597,P0.001)。經(jīng)Meta分析后,淋球菌對頭孢泊肟的敏感性檢測率為92.8%(95CI：89.0%-95.3%),并且比頭孢克肟的敏感性檢測率低(92.8% vs.99.8%, χ2=951.809, P0.001)。經(jīng)Meta分析后,淋球菌對阿奇霉素的耐藥率為6.3%(95%CI 3.3-11.6%).亞組分析發(fā)現(xiàn),在2008年前收集的淋球菌對阿奇霉素的耐藥率比2008年及以后收集的淋球菌對阿奇霉素的耐藥率低(2.0% vs.12.5%, χ2=27.650, P0.001)。廣東地區(qū)淋球菌對阿奇霉素的耐藥率最高,其次為南京、重慶地區(qū),最低為山東河北地區(qū)(χ2=22.321,P0.001)。[結(jié)論]在世界范圍內(nèi),總體來講淋球菌對頭孢克肟敏感,但淋球菌對頭孢克肟的敏感性在不同性別、不同地區(qū)存在差異,并且隨著時間的變化逐漸降低,且淋球菌對頭孢泊肟敏感性較頭孢克肟低。在中國地區(qū)淋球菌對阿奇霉素的敏感性有地區(qū)差異,特別是廣東省,阿奇霉素不宜單獨(dú)作為治療淋病的一線用藥。第二部分：淋球菌對頭孢克肟及其他抗生素的敏感性及MLVA分型研究[目的]了解中國地區(qū)淋球菌臨床分離菌株對頭孢克肟及其他抗生素的敏感性及獲取多位點(diǎn)串聯(lián)重復(fù)序列分型(Multiple-locus variable number tandem repeat ananlysis, MLVA)生物學(xué)信息。[方法]2012年在廣州、南京和天津地區(qū)性病門診收集244株淋球菌臨床分離菌株,檢測其對青霉素、四環(huán)素、環(huán)丙沙星、壯觀霉素、頭孢曲松和頭孢克肟的敏感性。應(yīng)用MLVA分型方法對244株淋球菌臨床分離菌株進(jìn)行基因分型。[結(jié)果]在廣州、南京和天津三個城市中,質(zhì)粒介導(dǎo)高度耐四環(huán)素淋球菌(Plasmid-mediated high level tetracycline-resistant Neisseria gonorrhoeae,TRNG) (χ2=26.418,P0.001)、頭孢曲松低敏菌株(χ2=4.417,P=0.093)、頭孢曲松低敏且頭孢克肟非敏感菌株(χ2=2.768,P=0.096)檢測率差異有統(tǒng)計學(xué)意義。頭孢曲松低敏菌株與廣州(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)和頭孢克肟低敏菌株(odds ratio 2.378,95%CI1.103-5.310,P=0.027)正相關(guān)。頭孢克肟非敏感菌株與產(chǎn)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)負(fù)相關(guān),與頭孢曲松非敏感菌株(odds ratio 2.017,95%CI 0.957-4.249, P=0.065)正相關(guān)。244株淋球菌臨床分離菌株進(jìn)行MLVA分型,共獲取110種基因型別和5個簇,其中簇Ⅲ與PPNG菌株相關(guān)(P=0.008),簇Ⅱ與非PPNG (P=0.008)及頭孢曲松低敏菌株相關(guān)(P=0.024)。[結(jié)論]在中國廣州、南京和天津地區(qū)可用頭孢曲松和壯觀霉素治療淋病,但青霉素、四環(huán)素和環(huán)丙沙星和頭孢克肟不適合用來推薦治療淋病。MLVA分型可用于淋球菌基因分型,并且淋球菌對抗生素的敏感性可能與某些簇相關(guān)。第三部分：頭孢曲松和阿奇霉素在體外抗淋球菌聯(lián)合作用的研究[目的]研究頭孢曲松和阿奇霉素在體外抗淋球菌的聯(lián)合作用。[方法]2012年在大連地區(qū)性病門診共收集25株淋球菌臨床分離菌株,用Etest法檢測頭孢曲松和阿奇霉素在體外抗淋球菌的聯(lián)合作用,計算部分抑菌濃度指數(shù)(Fractional inhibitory concentration index, FICI)判斷頭孢曲松和阿奇霉素在體外抗淋球菌的聯(lián)合作用。[結(jié)果]共檢測25株大連地區(qū)收集的淋球菌臨床分離菌株,FICI在0.724-2.696之間,頭孢曲松和阿奇霉素對所有淋球菌臨床分離菌株都有相加作用,無協(xié)同作用,但也無拮抗作用。[結(jié)論]頭孢曲松和阿奇霉素聯(lián)合使用治療淋病可能是未來中國推薦指南的一個選擇。
[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.

【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級別】：博士
【學(xué)位授予年份】：2015
【分類號】：R759.2

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