四川省猪源沙门氏菌及耐药性变迁调查

为了解四川地区近几年猪源沙门氏菌的耐药性变迁情况,本研究于2009—2014年间采集了四川省主要猪养殖场的肛拭子样本2660份,分离鉴定获得沙门氏菌151株,总分离率为5.68%,占主导的血清型为德尔卑沙门氏菌(60.26%)。采用微量肉汤稀释法测定分离菌株对13种抗菌药物的敏感性。药敏结果显示,沙门氏菌对氨苄西林、阿莫西林/克拉维酸、大观霉素、四环素、磺胺异噁唑、复方新诺明和恩诺沙星7种药物的耐药率最高,分别为94.7%、92.7%、93.4%、95.4%、91.4%、90.1%和86.8%,对头孢噻呋和多粘菌素E相对敏感。分析猪源沙门氏菌对不同抗菌药物的耐药性随年份的变迁情况,结果表明:2009—2014年猪源沙门氏菌对氨苄西林、阿莫西林/克拉维酸、大观霉素、四环素、磺胺异噁唑和复方新诺明6种药物的耐药率维持较高的平稳动态趋势,对头孢噻呋、庆大霉素、多西环素、氟苯尼考、恩诺沙星、氧氟沙星和多粘菌素E这7种药物的耐药率呈上升趋势,尤其对头孢噻呋、多西环素、氟苯尼考和氧氟沙星的耐药率上升显著。6年间多重耐药菌株比例维持在较高水平(>60%)。研究表明,四川地区猪源沙门氏菌的耐药情况十分严重,亟需加强养殖业抗菌药物的合理应用以控制耐药性发展。     

上呼吸道感染患儿咽部病原菌分布及耐药性分析

目的了解天津滨海地区儿童上呼吸道感染病原菌情况及耐药性,以便指导临床合理用药。方法对2012年1月至2013年4月天津市滨海新区汉沽中医医院住院儿科1022例上呼吸道感染儿童咽拭子标本进行培养及鉴定。采用法国ATB自动细菌鉴定仪及MIC药敏板进行细菌鉴定和药敏试验,β-内酰胺酶试验采用头孢硝噻吩纸片法,耐甲氧西林金黄色葡萄球菌（MRSA）采用头孢西丁纸片法检测。结果检出病原菌296株,其中金黄色葡萄球菌、肺炎链球菌及流感嗜血杆菌检出率分别为13. 70%、5. 97% 、5. 19%,分列前三位。金黄色葡萄球菌对常用抗菌药物耐药率为苯唑西林30. 0%、青霉素95. 7%、红霉素80. 0%、左氧氟沙星4. 3%,MRSA占30. 0% （42/140）、;肺炎链球菌对常用抗菌药物耐药率为青霉素9. 84%、红霉素54. 1%、克林霉素52.5%、左氧氟沙星3. 3% ;流感嗜血杆菌对常用抗菌药物耐药率为氨苄西林34. 0%、阿奇霉素0%、左氧氟沙星0%,复方新诺明56. 6%、头孢呋辛3. 8%、阿莫西林/克拉维酸5. 7%。结论天津滨海地区儿童上呼吸道感染病原菌分布广泛,检出致病菌有一定的耐药率,临床应重视根据病原菌感染情况及药敏试验结果,进行耐药性监测和合理用药。     

全基因组测序技术对沙门氏菌血清型和耐药性的预测能力分析

[目的] 评价全基因组测序技术在沙门氏菌血清型和耐药性检测方面的应用能力。[方法] 对我国1950-2015年分离的290株鸡源沙门氏菌用常规检测方法进行了血清分型和药敏试验;提取全基因组进行测序,应用SeqSero和ResFinder数据库分析沙门氏菌的血清型和耐药性;对用常规检测方法和全基因组测序分析方法得到的血清型和耐药性结果进行比较,分析两种方法所得结果的符合性情况。[结果] 沙门氏菌的主要血清型为肠炎和鸡白痢（≥84.5%）,常规检测方法和全基因组测序分析方法在沙门氏菌血清分型方面的总体符合率为97.6%。对11种抗菌药物的最小抑菌浓度（MIC）检测结果显示,沙门氏菌对磺胺异噁唑（39.3%）、氨苄西林（39.0%）和粘菌素（39.0%）的耐药率较高,对其他抗菌药物的耐药率较低。全基因组测序分析能够100%预测美罗培南、氟苯尼考、阿奇霉素和阿莫西林/克拉维酸的耐药性,而且对恩诺沙星、四环素、复方新诺明、氨苄西林、头孢噻呋、磺胺异噁唑的预测符合率均超过95.0%。[结论] 本研究结果表明,全基因组测序技术对沙门氏菌的血清分型和耐药性的预测具有较高的准确性和敏感性,是分析沙门氏菌血清型和耐药性的有效工具,具备良好的应用前景。     

近12年下呼吸道感染病原菌变迁及耐药性分析

目的:了解1996-2007年湘雅医院呼吸科下呼吸道感染住院患者病原茵变迁及耐药性情况.方法:对呼吸病房下呼吸道感染住院患者痰菌(或支纤镜吸取分泌物)培养阳性标本结果进行回顾性统计分析.结果:分离出细菌2966株,其中革兰阴性杆菌占86.9%,病原菌主要为铜绿假单胞菌、肺炎克雷伯菌、鲍曼不动杆菌、副流感嗜血杆菌、大肠埃希菌和流感嗜血杆菌;革兰阳性球菌占13.1%,主要病原菌为金葡菌和肺炎链球菌.近四年革兰阴性杆菌有所增加,而革兰阳性球菌有所减少.革兰阴性杆菌中,副流感嗜血杆菌和流感嗜血杆菌的比例明显升高;革兰阳性球菌中,金黄色葡萄球茵比例降低、肺炎链球菌比例升高.药敏试验结果提示主要革兰阴性杆菌对美洛培南、头孢哌酮/舒巴坦、阿米卡星均较敏感.铜绿假单胞菌还对头孢他啶、哌拉西林/他唑巴坦、氨曲南敏感性高,对头孢曲松、氨苄西林/舒巴坦、头孢噻肟耐药率增高.鲍曼不动杆菌对氨苄西林/舒巴坦敏感性较好,但耐药率有增高趋势,对头孢噻肟、头孢他啶、环丙沙星耐药率明显增高.肺炎克雷伯菌和大肠埃希菌对头孢哌酮、头孢曲松、头孢噻肟、头孢他啶、氨苄西林/舒巴坦耐药率增高;但二者对头孢他啶仍然保持相对敏感,耐药率为25.3%和27.6%.嗜血杆菌属中,流感嗜血杆菌与副流感嗜血杆菌的敏感抗生素谱相似,均对强力霉素、壮观霉素、头孢类抗生素耐药性低,而对喹诺酮类和青霉素敏感性差.主要革兰阳性球菌对阿奇霉素、克林霉素、红霉素及青霉素耐药率均较高;二者对红霉素耐药率明显增高.其中金葡菌对万古霉素均敏感,对左氟沙星、苯唑青霉素、头孢唑啉、美洛培南、强力霉素耐药率均明显增高.肺炎链球菌还对美洛培南、左氟沙星耐药率低,耐药率无明显增高.结论:近年下呼吸道感染病原菌以革兰阴性杆菌为主;主要病原菌对大部分抗菌药物的耐药率有逐渐增高的趋势,临床应合理应用抗菌药,以延缓细菌耐药性的产生.     

细菌性前列腺炎病原菌及临床耐药情况分析

目的 分析汕头地区慢性前列腺炎（CP）病原菌的分布及耐药情况,为确定病原菌分布情况和临床治疗提供参考依据。方法 细菌鉴定及药敏试验采用VITEK-60全自动细菌鉴定仪。结果 葡萄球菌是汕头地区CP的主要致病菌（67％）,其中表皮葡萄球菌的检出率最高,为21．58％。葡萄球菌引起的CP对苯唑西林、头孢唑林、氨苄西林-舒巴坦、阿莫西林-克拉维酸和红霉素等基本无效;而肠球菌对青霉素耐药率为0。治疗首选万古霉素、呋喃妥因、克林霉素和利福平等抗生素。结论 该地区CP的致病菌以葡萄球菌为主,其中表皮葡萄球菌已成为CP的主要病原菌。为减少浪费、提高疗效,建议根据药敏结果选择抗生素。     

老年患者难愈性创面的病原菌分布及耐药性

目的分析老年患者难愈性创面的病原菌分布及耐药情况。方法对2011年1月至2014年12月间中国人民解放军第八五医院烧伤外科收治老年难愈性创面患者创面分离出的病原菌,采用VITEK2全自动微生物分析仪对病原菌进行鉴定,K-B纸片扩散法进行药物敏感试验,数据统计采用SPSS 17.0软件处理。结果分离出病原菌132株,其中革兰阳性菌28株(21.21%),革兰阴性菌104株(78.79%)。常见病原菌为铜绿假单胞菌(42株,31.82%)、金黄色葡萄球菌(21株,15.91%)、大肠埃希菌(20株,15.15%)和鲍曼不动杆菌(16株,12.12%)。革兰阳性菌对青霉素、氨苄西林、红霉素、克林霉素、环丙沙星、氨苄西林/舒巴坦、阿莫西林/克拉维酸、头孢曲松的耐药率高于70%,对万古霉素、利奈唑烷、达托霉素和奎奴普丁/达福普汀的耐药率均为0%。革兰阴性菌对氨苄西林、阿莫西林/克拉维酸、头孢唑林、替卡西林/克拉维酸的耐药率高于70%,对头孢噻肟、左氧氟沙星、头孢呋辛、头孢吡肟的耐药率介于50%~70%,对美罗培南、亚胺培南、头孢哌酮/舒巴坦的耐药率低于30%。结论老年患者难愈性创面病原菌以革兰阴性菌居多,病原菌耐药严重,应引起临床重视。     

四川绵阳地区肺炎链球菌流行病学特征

目的了解四川绵阳地区肺炎链球菌的耐药情况,为临床合理用药及感染控制提供依据。方法收集我院2015年1月至2017年12月临床分离的718株肺炎链球菌,并对其药物敏感性检测结果进行分析。结果肺炎链球菌对红霉素和四环素的耐药率最高,均在95%以上;对左氧氟沙星、莫西沙星、泰利霉素、氯霉素的敏感性较高,均在89%以上;对青霉素、美罗培南、阿莫西林和头孢类抗生素的耐药率均在30%以上;未检出万古霉素和利奈唑胺耐药株。肺炎链球菌主要耐药模式为头孢曲松+红霉素+四环素+复方新诺明+美罗培南+青霉素+阿莫西林+头孢噻肟,占19.44%。2017年肺炎链球菌青霉素敏感株和不敏感菌株对美罗培南、阿莫西林、厄他培南、头孢噻肟、头孢曲松、氧氟沙星、复方新诺明和氯霉素的不敏感率比较差异有统计学意义(P0.05)。结论本地区肺炎链球菌对红霉素、四环素耐药率较高,不适用于肺炎链球菌感染的治疗;对青霉素、美罗培南、阿莫西林和头孢类抗生素不敏感率较高,应慎重用于经验治疗;对万古霉素、利奈唑胺和喹诺酮类药物敏感性较高,临床可合理使用。     

2016-2018年医院血培养病原菌的分布及耐药性分析

目的:分析2016-2018年医院血培养病原菌的分布及其耐药性。方法:对2016年1月至2018年12月遵义医科大学附属医院各科室送检的血标本进行培养、鉴定和药敏试验,并对主要病原菌的分布和药敏结果进行统计分析。结果:2016-2018年分别分离出病原菌1459、1647、1711株,其中革兰氏阴性杆菌分别为占57.78%、55.43%、54.24%,革兰氏阳性球菌分别占37.97%、39.34%、43.25%,真菌分别占4.25%、5.22%、2.51%。2016-2018年,大肠埃希菌对头孢呋辛、头孢曲松的耐药率逐年降低,对厄他培南耐药率呈明显的升高趋势;肺炎克雷伯菌对头孢呋辛、头孢曲松、头孢吡肟的耐药率逐年降低,对头孢哌酮/舒巴坦、氨苄西林/舒巴坦耐药率上升;凝固酶阴性葡萄球菌对左氧氟沙星、苯唑西林、庆大霉素的耐药率明显降低,对环丙沙星、克林霉素的耐药率有明显的上升趋势;金黄色葡萄球菌对环丙沙星、克林霉素的耐药率明显升高,对左氧氟沙星的耐药率明显降低,对呋喃妥因、万古霉素、利奈唑胺、替加环素均不耐药;白色假丝酵母菌、热带假丝酵母菌对两性霉素B均不耐药,白色假丝酵母菌对氟康唑、伏立康唑不耐药,热带假丝酵母菌对氟康唑、伊曲康唑均高度耐药。结论:造成血流感染(BSI)的主要病原菌为革兰氏阴性杆菌,病原菌对常用的抗菌药物都有不同程度的耐药,临床应合理使用抗菌药物,以降低耐药性,并加强医院感染控制措施减少耐药菌的传播。     

2004至2005年我院嗜血杆菌的分离及其耐药性

目的了解我院2004至2005年流感嗜血杆菌的分离率、产酶率,并对其耐药性进行分析,指导临床合理用药控制嗜血杆菌的流行。方法对1695份痰及咽拭子标本进行嗜血杆菌分离培养、鉴定,并用头孢硝噻吩纸片法进行β-内酰胺酶测定,采用琼脂扩散法进行药敏试验。结果共分离出226株嗜血杆菌,其中流感嗜血杆菌52株,副流感嗜血杆菌174株。产β-内酰胺酶42株,对氨苄西林、复方新诺明、环丙沙星的耐药率分别为22.1%、74.3%和57.5%。而对阿莫西林/棒酸、阿奇霉素、头孢噻肟、头孢呋辛钠、亚胺培南、利福平、氨曲南的耐药率均低于10%。结论我院呼吸道嗜血杆菌感染以副流感嗜血杆菌为主,临床上治疗嗜血杆菌感染最有效的药物是头孢噻肟。     

眼分泌物耐甲氧西林表皮葡萄球菌检测及耐药性分析

目的 探讨眼科分泌物中表皮葡萄球菌耐药特征,指导临床合理使用抗菌药物.方法 用定量接种针挑取单个菌落溶于0.5 McFarland硫酸钡接种液制成混悬液,再用接种器吸取菌液接种于Pos Combo Panel Type20,35℃孵育24 h,应用美国德灵SCAN4微生物分析仪对192株葡萄球菌中的86株表皮葡萄球菌进行鉴定和药敏试验.结果 表皮葡萄球菌检出86株,检出率为44.8％ (86/192);MRSE检出58株,检出率为30.2％ (58/192),MRSE占表皮葡萄球菌的67.4％ (58/86);MRSE对头孢西丁、青霉素、红霉素、阿莫西林/克拉维酸、头孢唑啉、复方新诺明、苯唑西林、左氧氟沙星、庆大霉素、亚胺培南具有显著耐药性,对万古霉素、利奈唑烷、利福平、四环素、氯霉素敏感.结论 眼科分泌物中表皮葡萄球菌耐药性严重,并且MRSE呈现多重耐药,医院应加强对MRSE的检测,依据药敏结果合理选用抗菌药物治疗感染.     

2019—2020年上海地区儿童幽门螺杆菌感染及其耐药性分析

为分析2019-2020年上海地区儿童幽门螺杆菌感染及其对4种常用抗菌药物的耐药状况,本研究收集了2019年1月-2020年10月于复旦大学附属儿科医院就诊且经胃镜检查、快速尿素酶试验阳性的患儿 1 605 例,取胃黏膜样本进行幽门螺杆菌分离培养及鉴定,采用E-test法进行体外药敏试验,分析不同年龄组患儿幽门螺杆菌耐药状况。结果显示,本研究入组患儿标本的幽门螺杆菌分离率为31.5%(506/1 605),无性别和年龄差异。幽门螺杆菌临床分离株对甲硝唑、克拉霉素、左氧氟沙星、阿莫西林的耐药率分别为42.3%、25.1%、8.1%、3.0%。除13～16岁组幽门螺杆菌对克拉霉素的耐药率显著高于1～3岁组(31.2% vs. 13.3%,P＝0.040)外,其他各年龄和性别组之间耐药率均无统计学差异。此外,幽门螺杆菌对克拉霉素＋甲硝唑的双重耐药率为18.0%,显著高于对克拉霉素＋左氧氟沙星(5.1%)、甲硝唑＋左氧氟沙星(4.9%)、甲硝唑＋阿莫西林(1.4%)和阿莫西林＋左氧氟沙星的耐药率(0.8%)(χ2＝172.706, P<0.01)。多重耐药分析显示,幽门螺杆菌对左氧氟沙星＋克拉霉素＋甲硝唑的耐药率为3.0%,显著高于对左氧氟沙星＋阿莫西林＋克拉霉素(0.6%)、阿莫西林＋甲硝唑＋左氧氟沙星的耐药率(0.6%)(χ2＝13.907,P＝0.01)。结果提示,2019--2020年从上海地区儿童分离的幽门螺杆菌对甲硝唑、克拉霉素的耐药率较高,对阿莫西林和左氧氟沙星的耐药率较低,对甲硝唑和克拉霉素的双重耐药率较高。     

Pharmacokinetics Study of Amoxycillin and Clavulanic acid (8:1)-A New Combination in Healthy Chinese Adult Male Volunteers Using the LC–MS/MS Method

New oral granules of amoxicillin and clavulanic acid in 8:1 ratio have recently been developed and approved to conduct clinical trial in China. To date, there has been no report studying the pharmacokinetic characteristics of amoxicillin and clavulanic acid in man. Therefore, it is urgent to investigate the pharmacokinetic properties of amoxicillin and clavulanic acid in man. The aim of the study was to assess the pharmacokinetic properties of amoxicillin and clavulanic acid in 8:1 with different dosage in healthy volunteers and provide support for this drug to obtain marketing authorization in China. A liquid chromatography-tandem mass spectrometry method for determining the concentration of amoxicillin and clavulanic acid in human plasma was developed and applied to this open-label, single- and multiple-dose Pharmacokinetics study. Subjects were randomized to receive a single dose of 1, 2, and 4 pouches of the test granulation of amoxicillin and clavulanic acid in 8:1 ratio (amoxicillin is 250 mg and clavulanic acid is 31.25 mg per pouch). In the single-dose phase, blood samples were collected before dosing and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 5, 8, 12, and 24 h after drug administration. In the multiple-dose phase, samples were obtained before drug administration on days 1, 2, 3, and 4 to determine the C_min of amoxicillin and clavulanic acid. In the 4th day, samples were collected from 0.25 to 24 h after drug administration. Profiles of the concentration–time curves of amoxicillin and clavulanic acid were best fitted to two-compartment model. In this group of healthy Chinese subjects, the pharmacokinetics of amoxicillin fitted the linear dynamic feature at doses of 250,500 and 1,000 mg, and not obviously about clavulanic acid at doses of 31.25, 62.5, and 125 mg. The t _1/2 of single dose and multidoses were (1.45 ± 0.12) and (1.44 ± 0.26) h of amoxicillin and (1.24 ± 0.23) and (1.24 ± 0.17) of clavulanic acid, respectively; The AUC_0–24 of single dose and multidoses were (27937.85 ± 4265.59) and (24569.80 ± 3663.63) ng h mL^?1 of amoxicillin and (891.45 ± 194.30) and (679.61 ± 284.05) ng h mL^?1 of clavulanic acid, respectively; The C_max of single dose and multidoses were (8414.58 ± 1416.78) and (7929.17 ± 1291.54) ng mL^?1 of amoxicillin and (349.00 ± 89.54) and (289.00 ± 67.36) ng h mL^?1 of clavulanic acid, respectively. t _1/2, AUC_0–24, and C_max were similar after multiple-dose administration and after single-dose administration, suggesting that amoxicillin and clavulanic acid do not accumulate with multiple-dose administration of 500 and 62.5 mg, respectively.     

产ESBLs肺炎克雷伯菌AmpC酶的检测及耐药性分析

目的了解深圳市人民医院产ESBLs肺炎克雷伯菌中产AmpC酶的情况及其耐药性。方法收集产ESBLs肺炎克雷伯菌临床株126株,应用Tris-EDTA纸片法检测AmpC酶。用琼脂稀释法测定菌株对11种抗生素的最低抑菌浓度（MIC）。结果126株ESBLs阳性的肺炎克雷伯菌中12株检出AmpC酶,检出率为9.5%。AmpC阳性菌株对头孢西丁、头孢他啶、氨曲南、氨苄西林/舒巴坦和阿莫西林/克拉维酸的耐药率达100%,对阿米卡星和哌拉西林/他唑巴坦的耐药率分别为83.3%和33.3%,其中头孢西丁、头孢他啶、氨曲南、阿莫西林/克拉维酸、阿米卡星和哌拉西林/他唑巴坦的耐药率显著高于AmpC阴性株（P〈0.05）。结论深圳市人民医院产ESBLs肺炎克雷伯菌中检出AmpC酶阳性株,其耐药性强于单产ESBLs菌株。     

Molecular Epidemiology of Nontypeable Haemophilus influenzae Causing Community-Acquired Pneumonia in Adults

Nontypeable Haemophilus influenzae (NTHi) is an opportunistic pathogen which causes a variety of respiratory infections. The objectives of the study were to determine its antimicrobial susceptibility, to characterize the β-lactam resistance, and to establish a genetic characterization of NTHi isolates. Ninety-five NTHi isolates were analyzed by pulsed field gel electrophoresis (PFGE) and multi locus sequence typing (MLST). Antimicrobial susceptibility was determined by microdilution, and the ftsI gene (encoding penicillin-binding protein 3, PBP3) was PCR amplified and sequenced. Thirty (31.6%) isolates were non-susceptible to ampicillin (MIC≥2 mg/L), with 10 of them producing β-lactamase type TEM-1 as a resistance mechanism. After ftsI sequencing, 39 (41.1%) isolates showed amino acid substitutions in PBP3, with Asn526→ Lys being the most common (69.2%). Eighty-four patients were successfully treated with amoxicillin/clavulanic acid, ceftriaxone and levofloxacin. Eight patients died due either to aspiration or complication of their comorbidities. In conclusion, NTHi causing CAP in adults shows high genetic diversity and is associated with a high rate of reduced susceptibility to ampicillin due to alterations in PBP3. The analysis of treatment and outcomes demonstrated that NTHi strains with mutations in the ftsI gene could be successfully treated with ceftriaxone or fluoroquinolones.     

大肠埃希菌和肺炎克雷伯菌ESBLs检测及耐药性分析

由细菌超广谱β-内酰胺酶（ESBLs）引起的细菌耐药性一直是临床相关感染性疾病治疗中的棘手问题。从不同病区患者标本中分离了96株大肠埃希菌和80株肺炎克雷伯菌,分剐采用双纸片协同试验和药物敏感试验检测了上述菌株产生ESBLs情况及对17种抗生素的耐药性。结果发现,27．1％（26／96）的大肠埃希菌株和22．5％（18／80）肺炎克雷伯菌株产ESBLs。ICU病房分离的大肠埃希菌和肺炎克雷伯菌株ESBLs总阳性率（46．0％）与介入科病房和烧伤科病房分离菌株ESBLs总阳性率（28．6％和25．0％）无显著性差异（P〉0．05）,但明显高于呼吸科、骨科、其他病房及门诊部分离菌株ESBLs总阳性率（6．3％～14．3％,P〈0．01）。不产ESBLs大肠埃希菌株和肺炎克雷伯菌株对17种抗生素耐药率明显低于产ESBLs菌株。产ESBLs大肠埃希菌和肺炎克雷伯菌对氨曲南均敏感,对氨苄西林／舒巴坦、阿莫西林／棒酸、阿米卡星耐药率仅为15．8％-23．4％。上述实验结果提示,大肠埃希菌和肺炎克雷伯菌临床菌株中有较高的ESBLs阳性率,不同病区患者感染的大肠埃希菌和肺炎克雷伯菌ESBLs阳性率有很大差异,氨曲南、氨苄西林／舒巴坦、阿莫西林／棒酸、阿米卡星可作为治疗产ESBLs大肠埃希菌和肺炎克雷伯菌感染性疾病的首选药物。     

Structural Variabilities in β-Lactamase (blaA) of Different Biovars of Yersinia enterocolitica: Implications for β-Lactam Antibiotic and β-Lactamase Inhibitor Susceptibilities

Yersiniosis caused by Yersinia enterocolitica has been reported from all continents. The bacterial species is divided into more than fifty serovars and six biovars viz. 1A, 1B, 2, 3, 4 and 5 which differ in geographical distribution, ecological niches and pathogenicity. Most Y.enterocolitica strains harbor chromosomal genes for two β-lactamases, blaA an Ambler class A penicillinase and blaB an Ambler class C inducible cephalosporinase. In the present study, susceptibility to b-lactam antibiotics and β-lactamase inhibitor was studied for Y. enterocolitica strains of biovars 1A, 1B, 2 and 4. We observed that β-lactamases were expressed differentially among strains of different biovars. To understand the molecular mechanisms underlying such differential expression, the sequences of genes and promoters of blaA were compared. Also, the variants of blaA present in different biovars were modeled and docked with amoxicillin and clavulanic acid. The mRNA secondary structures of blaA variants were also predicted in-silico. Our findings indicated that neither variations in the promoter regions, nor the secondary structures of mRNA contributed to higher/lower expression of blaA in different biovars. Analysis of H-bonding residues of blaA variants with amoxicillin and clavulanic acid revealed that if amino acid residues of a β-lactamase interacting with amoxicillin and the clavulanic acid were similar, clavulanic acid was effective in engaging the enzyme, accounting for a significant reduction in MIC of amoxicillin-clavulanate. This finding might aid in designing better β-lactamase inhibitors with improved efficiencies in future.     

Randomized comparison of two non-bismuth-containing second-line rescue therapies for Helicobacter pylori

Background: Classical second‐line anti‐Helicobacter pylori includes proton‐pump inhibitor, tetracycline, metronidazole, and bismuth salts, but alternative therapies are required owing to the restricted availability of the latter. Levofloxacin‐containing triple therapy is recommended but is expensive. Besides, quinolone resistance in an endemic tuberculosis infection area like Taiwan is concerned. The low in vitro antibiotic resistance to amoxicillin and tetracycline in Taiwanese H. pylori strains implies that in vivo esomeprazole/amoxicillin/tetracycline (EAT) second‐line rescue therapy may be effective. This study compared the efficacy of esomeprazole/amoxicillin/levofloxacin (EAL) and EAT second‐line eradication therapies and determines the clinical factors influencing the efficacy of salvage regimens. Materials and methods: One hundred and twenty‐eight patients who failed H. pylori eradication using the standard triple therapy for 7 days are randomly assigned to either EAL group (esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, and levofloxacin 500 mg once daily) for 7 days or EAT group (esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, tetracycline 500 mg four times daily) for 14 days. Follow‐up endoscopy or urea breath test was performed 8 weeks later to assess treatment response. Results: The eradication rates of EAL and EAT groups were 78.1 versus 75.0%, p = .676 (in intention‐to‐treat analysis) and 80.3 versus 80%, p = .0964 (per‐protocol analysis). Both groups exhibited similar drug compliance (95.3 vs 96.9%, p = .952) but more adverse events in the EAT group (6.3 vs 12.5%, p = .225). Conclusions: Despite low in vitro drug resistances to amoxicillin and tetracycline, the efficacy of 14‐day EAT regimens attained an unacceptable report card of 75% eradication rates in intention‐to‐treat analysis and was not even superior to the 7‐day EAL regimen. Drug–drug interaction between combined antibiotics should be considered other than in vivo drug resistances.