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Multiple genes encoding fluoroquinolone resistance co-located with ESBL genes in non-typhoidal salmonella isolated from food producing animals

Multiple genes encoding fluoroquinolone resistance co-locate...

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中国药理学会第十一届全国化疗药理学术研讨会

作者： Xiao-Ping Fu,Yu-Fang Guo,Li-Hua Wang,Jun-Yu Ren,Hong-Xia Jiang College of Veterinary Medicine,National Reference Laboratory of Veterinary Drug Residues,South China Agricultural University(SCAU),Guangzhou 510642,China )

OBJECTIVES To investigate the molecular epidemiology of genes that confer resistance to fluoroquinolones and extended spectrum(1 -lactams in non-typhoidal Salmonella(NTS) from food producing animals in *** Thirty-one non-duplicate NTS were examined by PCR for plasmid mediated ESBL(TEM,SHV,OXA,CMY,and CTX-M-9),fluoroquinolone-resistance(qnr,aac(6' )-Ib-cr,qepA and oqx) *** QRDR of topoisomerase genes (gyrA,gyrB,parC and parE) was also *** relatedness of isolates was determined by PFGE;susceptibility to antibiotics was measured with CLSI *** Numerous combinations of different antibiotic resistance genes and mutations in topoisomerase genes were *** most concern was that different isolates of Salmonella each contained several antibiotic resistance genes which together conferred high level resistance to extended spectrum(3 -lactams and *** These data suggest that contamination of food by multi-drug resistant bacteria in exporting countries with highly mobile populations will lead to global transfer of new antibiotic resistances from country to country by humans or on *** infections by such strains would be hard to treat.

关键词： plasmid Salmonella fluoroquinolone ESBL

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Development and validation of a new UPLC method for vancomycin and comparison to FPIA(TDx)

Development and validation of a new UPLC method for vancomyc...

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中国药理学会第十一届全国化疗药理学术研讨会

作者： Yuran Cao,Jing Zhang (Institute of Antibiotics Hua-shan Hospital,Fudan University & Key Laboratory of Clinical Pharmacology of Antibiotics,Ministry of Health,Shanghai 200040)

A ultra performance liquid chromatographic（UPLC） method with photo-diode array（PDA） detection for the quantification of vancomycin in human plasma was developed and *** method included an extraction of vancomycin by deproteinization with *** analyses were carried out at 230 nm as the detcet wavelength on a ACQUITY UPLC BEH C18 column（2.1 x 50 mm,1.7um） using a mobile phase composed of acetonitrile and 5 mM KHPO buffer at pH *** calibration curve was linear over the range from 1 to 100 mg/L（R2 higher than 0.999）.The method was validated via extraction recovery,intra- and inter-day methodological recovery and stability of vancomycin in *** used both established UPLC method and FPIA with vancomycin Kit to measure the serum vancomycin concentrations in 172 clinical samples,which were collected from the patients receiving vancomycin in the hospitals localized in Shanghai,China. Correlation analysis between the measurements of UPLC and FPIA in 172 serum samples gave the linear regression equation: （concentration by UPLC） = 0.949 *（concentration by FPIA） - 0.517（R = 0.923）.Thanks to the short analysis time and small quantities of plasma needed,this UPLC method developed in this study can be easily used for vancomycin TDM.

关键词： ultra high performance liquid chromatography(UPLC) vancomycin fluorescence polarization immunoassay(FPIA) therapeutic drug monitoring(TDM)

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The intra-herbal network effect of germacrone,curdione,and furanodiene combination on breast cancer cell proliferation

The intra-herbal network effect of germacrone,curdione,and f...

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中国药理学会第十一届全国化疗药理学术研讨会

作者： Xiuping Chen (State Key Laboratory of Quality Research in Chinese Medicine,Macau,China Institute of Chinese Medical Sciences,University of Macau,Macau,China )

Traditional Chinese medicine(TCM) has been considered as "Hard to swallow" due to limited rational mechanism of action for most of its *** efforts and attempts have been made to dissect the action mode of TCM in recent years,which provided certain evidence for the inter-herbal interactions in TCM ***,the intra-herbal interactions have been largely neglected as each TCM herb containing dozens of components was replaced by a single pure compound in most *** present study,we asked,whether there are interactions among different components from a single *** effect of three main sesquiterpenes(germacrone(A),curdione(B),furanodiene(C)) isolated from a common TCM herb called WenEZhu(Curcuma Wenyujin *** et C Ling) on MDA-MB-231 and MCF-7 breast cancer cells proliferation alone or in combination with a fixed-dose-combination has been *** significantly inhibit cancer cells proliferation while germacrone and curdione showed no *** enhanced furanodiene' s anti-proliferative *** showed no effect on furanodiene' s anti-proliferative effect but partly reverse the anti-proliferative effect of germacrone and furanodiene *** morphological and mitochondrial membrane potential(△Ψm) changes showed similar ***,they demonstrated complicated interaction on the protein expressions of apoptotic-related proteins and key signaling transduction *** herb might be a network system with complex and unpredictable interactions among different *** intra-herb interactions should be taken into consideration when attempts are made to interpret the art of Chinese medical formulae or other similar recipes.

关键词： Curcuma *** C Ling proliferation breast cancer cell intra-herbal drug interactions Chinese medicine

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化疗相关认知功能障碍的病理机制研究进展

化疗相关认知功能障碍的病理机制研究进展

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第十一届海峡两岸心血管科学研讨会、2017年全国心脑血管药理学术会议、中国卒中学会第一次新药研讨会

作者：王甜甜韩峰浙江大学医学院附属邵逸夫医院浙江大学药学院

化疗是针对各类癌症最基础的治疗方法,不仅引起严重的躯体不良反应,如恶心、呕吐、骨髓抑制等,而且可以引起中枢神经系统的急性和迟发性毒性。随着癌症诊断和治疗的不断突破,癌症患者的生存时间得以延长,癌症也被认为是一种慢性病,改善... 详细信息

化疗是针对各类癌症最基础的治疗方法,不仅引起严重的躯体不良反应,如恶心、呕吐、骨髓抑制等,而且可以引起中枢神经系统的急性和迟发性毒性。随着癌症诊断和治疗的不断突破,癌症患者的生存时间得以延长,癌症也被认为是一种慢性病,改善患者的生存质量逐渐成为临床治疗的目标之一。化疗引起的认知功能障碍(chemotherapy-induced cognitive impairment CICI),俗称化疗脑对患者的生活能力造成了很大的影响,近些年引起了临床医生的关注,与之相关的基础研究逐渐趋热。迄今为止,虽然CRCI的发病机制在很大程度上仍未知,但是一些可能的重要机制已经得以确认,本文就CRCI的发病机制进行综述。临床针对乳腺癌患者的研究发现,CRCI可以出现在疾病进展的不同阶段,其发生与化疗药物的剂量相关而且可以出现在各类化疗药物的治疗中,在化疗结束后几个月甚至几年内持续存在,但是,也有报道在化疗结束后该病得以改善。临床主要通过神经影像学方法研究CRCI的病理机制,常用的有核磁共振成像(MRI)、弥散张量成像(DTI)、功能性磁共振成像(fMRI)、正电子发射断层成像和脑电图等。研究发现,化疗使患者的灰质体积和白质连接广泛减少并且改变了大脑的功能活性和连接,此外,研究还发现CRCI患者中与疲乏、抑郁和焦虑相关的神经生物分子的改变。在基础研究中,一般认为CRCI的发生与化疗药物的直接毒性作用和间接作用相关。化疗药物的直接毒性作用取决于该类药物并非靶向药物,可能通过血脑屏障直接损伤包括神经祖细胞和有丝分裂后期少突细胞在内的各类细胞,甚至直接影响各种神经生物过程,产生认知损伤。化疗药物对认知功能损伤的间接机制包括破坏机体的氧化平衡状态,该状态在调控神经干细胞和祖细胞的功能方面起关键作用;持续引发神经炎症,从而影响髓鞘形成和认知功能;此外,还对神经递质的释放、正常的血管密度和血液供应产生不利作用。CRCI具体的发病机制仍处于初步探索阶段,该疾病的发生可能是多条作用机制共同作用的结果,与遗传因素、机体状态和药物性质等均有一定的关系。研究CRCI复杂的发病过程,可能有助于揭示神经血管相关疾病的复杂病理机制,具有重要的研究价值。

关键词：化疗药物病理机制功能障碍

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Alterations in the intracellular Ca2+ concentration and vimentin in endothelial cells following tumor cell-endothelial cell interactions

Alterations in the intracellular Ca2+ concentration and vime...

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中国药理学会第十一届全国化疗药理学术研讨会

作者： Yan PAN,Xuejun LI (State Key Laboratory of Natural and Biomimetic Drugs,Department of Pharmacology, School of Basic Medical Sciences,Peking University and Institute of System Biomedicine, Peking University,Beijing 100191,China )

Objective Interactions of tumor cells with endothelial cells（ECs）,for example tumor cell adhesion and migration through the EC layer,are essential components of tumor *** calcium regulation and cytoskeletal proteins in both tumor cells and ECs provide important signaling mechanisms for the growth,angiogenesis and metastasis of tumor *** the present study,we investigated the influence of tumor cell-EC interactions on the intracellular calcium ion concentration([Ca]) and vimentin in ***[Ca] was measured by confocal microscopy in human umbilical vein endothelial cells（HUVECs） before and after the addition of PC-3M prostate carcinoma *** expression and structural organization of vimentin in HUVECs was analyzed by immunofluorescence *** effect of heparin and nifidipine on EC[Ca] and vimentin were ***,a known disruptor of intermediate filaments,was used to induce the collapse of vimentin filaments,and the distribution of calcium ions in ECs was *** PC-3M cells induced a rapid[Ca] elevation and lead to altered vimentin distribution in ECs at the sites of tumor cell-EC *** cell-induced[Ca] elevation was significantly inhibited by heparin and nifidipine;heparin could preserve endothelial cells to pretend a more normal vimentin structure;however,nifidipine had no obvious effects on the expression and organization of ***-induced collapse of vimentin filaments shifted the distribution of calcium ions from the cytoplasm to the nucleus and perinuclear field in ***,acrylamide could not inhibit tumor cell-induced[Ca] *** Rapid[Ca] elevation and alterations in vimentin distribution occur in ECs at the sites of tumor cell-EC contact;the structural integrity of vimentin is partly related to the intracellular calcium ion distribution and concentration.

关键词： Calcium ions vimentin tumor cell-endothelial cell interaction.

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卡铂在ICR小鼠体内的组织分布研究

卡铂在ICR小鼠体内的组织分布研究

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中国药理学会第十一届全国基础与临床生殖药理学术研讨会暨生殖药理新技术与新方法培训班

作者：李钊郭湘洁朱焰上海市计划生育科学研究所生殖药理组国家人口和计划生育委员会计划生育药具重点实验室上海生殖健康药具工程技术研究中心

目的:建立测定ICR小鼠血浆和组织中卡铂含量的方法,测定卡铂在ICR小鼠体内不同时间点不同组织中浓度的变化,初步探讨卡铂在ICR小鼠体内的组织分布特征。方法:ICR小鼠24只,雌雄各半,雌雄分别按体重随机分为4组,每组3只,分别腹腔注射给予... 详细信息

目的:建立测定ICR小鼠血浆和组织中卡铂含量的方法,测定卡铂在ICR小鼠体内不同时间点不同组织中浓度的变化,初步探讨卡铂在ICR小鼠体内的组织分布特征。方法:ICR小鼠24只,雌雄各半,雌雄分别按体重随机分为4组,每组3只,分别腹腔注射给予卡铂（60mg/kg）。分别于给药后的5min、30min、60min、240min,解剖采集不同脏器组织(心、肝、脾、肺、肾、子宫（♀）、卵巢（♀）、睾丸（♂）、附睾（♂）、膀胱、骨骼肌);不同时间点的不同脏器分别使用匀浆机制备组织匀浆液,匀浆液采用蛋白沉淀的方式进行处理,并用液质联用（HPLC-MS/MS）检测各时间点血浆和组织器官药物浓度。采用Waters Atlantis T3 （3μm,100×2.1mm）色谱柱进行样品分析,柱温:40℃,以乙腈（10mM甲酸铵）-水（10mM甲酸铵、0.1%甲酸）为流动相,梯度洗脱:0-2min:2%-98%B,2-2.5min:98%B,2.51-4.0min:2%B;流速:0.3ml/min;MRM检测（ESI源）,用于定量分析的离子反应分别为m/z 372.20→294.10 （卡铂）和m/z 376.30→298.20（内标:氘代卡铂）。结果:卡铂各组织样品2.50～5000.00 ng·mL内线性关系良好,精密度、准确度、稳定性均能符合生物样品分析的要求。组织分布结果表明卡铂在ICR小鼠体内组织均有分布,组织内浓度依次为:肺>肝≈脾≈肾>心>睾丸>卵巢>子宫>附睾>膀胱>肌肉。结论:本实验测定ICR小鼠各组织中卡铂药物浓度的方法,具有快速、稳定、专属性高的特点,可以用于卡铂血浆及组织的测定。

关键词： ICR 分布研究

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Prevalence and molecular typing of the antiseptic resistance genes qacA/B among Staphylococcus aureus strains isolated in a teaching hospital

Prevalence and molecular typing of the antiseptic resistance...

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中国药理学会第十一届全国化疗药理学术研讨会

作者： Xiao Yu Wei,Tao Luo,Bei Jia,Li Jun Chang,Xiao Qiang Li,Wen Xiang Huang (l.Key Laboratory of Infectious and Parasitic Diseases in Chongqing,Infectious Disease Department,First Affiliated Hospital of Chongqing Medical University,Chongqing,China 2.Infectious Disease Department, Yuncheng City Central Hospital,Shanxi,China)

Background The qacA/B genes are found in Staphylococcus aureus and confer resistance to various antiseptics and ***,the prevalence of the qacA/B genes in methicillin-resistant ***(MRSA) and methicillin-sensitive ***(MSSA) is *** typing systems are used to analyse the relatedness of these qacA/ S-positive *** One hundred and seventy-six strains of clinically isolated *** were collected between July 2008 and June *** strains carrying the qacA/B genes were characterised by pulse-field gel electrophoresis(PFGE) typing,Staphylococcus protein A(spa) typing,Panton-Valentine leucocidin(pvl) PCR detection,staphylococcal chromosomal cassette(SCC) mec typing,and antimicrobial resistance *** Strains carrying the qacA/B genes composed 9.1% of the strains isolated,but the incidence of qacA/B genes in MRSA strains was significantly higher than that in MSSA strains (14.6%versus 4.3%,p<0.05).Additionally,two predominant PFGE(B and A) and spa types(t037 and t042) were identified along with two major antimicrobial resistance *** of these qacA/B-positive strains strains were pvl-negative by *** qacA/B-positive MRSA strains all contained the group III SCCmec *** strains were obtained mainly from patients in surgical wards;therefore,the neurosurgical ward and ICU may be considered as a source of MRSA strains carrying the qacA/B ***,the strain identified as spa type t037 is likely to be an epidemiological *** The presence of the antiseptic resistance genes qacA/B by MRSA could potentially lead to MRSA strain ***,the optimal usage of antiseptics and disinfectants is warranted.A policy of molecular typing needs to be implemented to track the possible dissemination of these resistance genes.

关键词： Prevalence and molecular typing of the antiseptic resistance genes qacA/B among Staphylococcus aureus strains isolated in a teaching hospital

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SM1044在大鼠体内的组织分布研究

SM1044在大鼠体内的组织分布研究

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中国药理学会第十一届全国基础与临床生殖药理学术研讨会暨生殖药理新技术与新方法培训班

作者：郭湘洁李钊钟瑞华朱焰上海市计划生育科学研究所生殖药理组国家人口和计划生育委员会计划生育药具重点实验室上海生殖健康药具工程技术研究中心

研究目的:建立测定大鼠血浆和组织中SM1044含量的方法,测定SM1044在SD大鼠体内不同时间点不同组织中浓度的变化,初步探讨SM1044在SD大鼠体内的组织分布特征。方法:雌性SD大鼠,9只,按体重随机分为3组,每组3只,分别腹腔注射给予SM1044（7m... 详细信息

研究目的:建立测定大鼠血浆和组织中SM1044含量的方法,测定SM1044在SD大鼠体内不同时间点不同组织中浓度的变化,初步探讨SM1044在SD大鼠体内的组织分布特征。方法:雌性SD大鼠,9只,按体重随机分为3组,每组3只,分别腹腔注射给予SM1044（7mg/kg）。分别于给药后的10min、60min、120min使用7%戊巴比妥钠麻醉后,解剖采集不同脏器组织（心、肝、脾、肺、肾、子宫、卵巢、膀胱、骨骼肌）;不同时间点的不同脏器分别使用匀浆机制备组织匀浆液,匀浆液采用液液萃取的方式进行处理,采用液质联用（HPLC-MS/MS）方法检测各时间点血浆和组织器官药物浓度。采用Phenomenex Kinetex 2.6u EVO C18 100A（2.6μm,100×2.1mm）色谱柱进行样品分析,柱温:40℃,以甲醇（4mM醋酸铵）-水（10mM醋酸铵、0.1%醋酸）为流动相,梯度洗脱:0-2min:70%-92%B,2-4min:92%B,4.01-7.5min:70%B;流速:0.35 ml/min;MRM检测（ESI源）,用于定量分析的离子反应分别为m/z 638.4→372.3（SM1044）和m/z 316.3→267.2 （内标蒿甲醚）。结果:SM1044各组织样品0.10～100.00 ng·mL内线性关系良好,精密度、准确度、稳定性均能符合生物样品分析的要求。组织分布结果表明SM1044在SD雌性大鼠体内主要分布于肺、子宫、卵巢及膀胱,心脏中也有少量分布。结论:本实验中建立测定SD雌性大鼠各组织中的SM1044药物浓度的LC-MS/MS方法,具有快速、稳定、专属性高的特点,其组织分布研究进一步的开发与临床应用SM1044提供了参考。

关键词：不同时间点雌性大鼠 SM1044 分布研究

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新化合物SM1044与顺铂联用抗人子宫内膜癌（hec-1a）的实验研究

新化合物SM1044与顺铂联用抗人子宫内膜癌（hec-1a）的实验研究

引用

中国药理学会第十一届全国基础与临床生殖药理学术研讨会暨生殖药理新技术与新方法培训班

作者：周洁芸杨文捷谢淑武李国停朱焰复旦大学生殖与发育研究院上海市计划生育科学研究所生殖药理组国家卫生健康委员会计划生育药具重点实验室

目的:研究新化合物SM1044单独和与顺铂联合应用,对Ⅰ型人子宫内膜癌细胞（hec-1a）荷瘤裸小鼠BALB/c-nu模型的影响。方法:体内建立heca荷瘤裸鼠动物模型,随机分成模型对照组、阳性对照组(顺铂3mg·kg+紫杉醇15mg·kg)、SM1044(7... 详细信息

目的:研究新化合物SM1044单独和与顺铂联合应用,对Ⅰ型人子宫内膜癌细胞（hec-1a）荷瘤裸小鼠BALB/c-nu模型的影响。方法:体内建立heca荷瘤裸鼠动物模型,随机分成模型对照组、阳性对照组(顺铂3mg·kg+紫杉醇15mg·kg)、SM1044(75mg·kg)、联合组(SM104475mg·kg+顺铂3mg·kg);SM1044灌胃给予每周3次,顺铂腹腔给予每周3次,紫杉醇腹腔给予每周1次,治疗3周后,对裸鼠体重和移植瘤体积、瘤质量的影响,并初步观察其有无毒性反应及毒性靶器官。结果:与治疗前相比,治疗三周后模型对照组体重显著增加（P<0.01）;阳性对照组（紫杉醇+顺铂）、SM1044(75mg·kg)、联合组（SM1044+顺铂）体重降低,其中阳性对照、联合组体重显著降低（P<0.01）。治疗前各组肿瘤体积无明显差异（P>0.05）;治疗结束后,与模型对照组相比,阳性对照组（紫杉醇+顺铂）、联合组（SM1044+顺铂）瘤体积、瘤重显著降低（P<0.01）,瘤体积抑制率分别为77.10%、89.22%;相对肿瘤增殖率T/C%分别为:23%、11%;SM1044(75mg·kg)瘤体积、瘤重明显降低（P<0.05）,T/C%为51%。治疗结束后,肉眼观察主要脏器无明显病变。与模型对照组相比,阳性对照组（紫杉醇+顺铂）心、肝脏系数显著升高（P<0.01）;SM1044(75mg·kg)脾脏系数明显升高（P<0.05）;联合组（SM1044+顺铂）心脏系数明显升高（P<0.05）。结论:SM1044对heca裸鼠移植瘤的生长具有抑制作用,且SM1044联用顺铂具有协同抗肿瘤的作用。

关键词：青蒿素衍生物顺铂人子宫内膜癌

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A Multicenter,Randomized Controlled Clinical Study on Ceftriaxone/Sulbactam and Cefoperazone/ Sulbactam Injection in the Treatment of Respiratory and Urinary Tract Infections caused by Resistant Bacteria

A Multicenter,Randomized Controlled Clinical Study on Ceftri...

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中国药理学会第十一届全国化疗药理学术研讨会

作者： Xiaojuan Xin~a,Bei Jia~(a*),Wenxiang Huang~a,Chongzhi Li~a,Changzheng Wang~b,Lixin Zhou~c, Xiuzhen Sun~d,Baosong Gui~d,Xinghuo Tang~e,Yunhua Liao~e,Yijiang Huang~f, Yunkui Zhu~g,Chunsheng Xi~g,Weili Zhang~h,Ling Zhong~h a.Key Laboratory of Infectious and Parasitic Diseases in Chongqing,Infectious Disease Department,First Affiliated Hospital of Chongqing Medical University,Chongqing,China b.Secondary Affiliated Hospital of the Third Military Medical University,Chongqing,China c.Renji Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai China d.Second Affiliated Hospital,Medicial School of Xi'an Jiaotong University,Xi'an,China e.First Affiliated Hospital of Guangxi Medical University,Nanning,China f.Hainan General Hospital,Haikou,China g.Lanzhou General Hospital of Lanzhou Military Area Command of Chinese PLA,Lanzhou China and h.Second Affiliated Hospital of Chongqing Medical University,Chongqing China

Background Ceftriaxone/sulbactam(4:1) is a novel p -lactam/ p -lactamase- inhibitor combination injection.A clinical study was designed to evaluate its efficacy and safety in the treatment of respiratory and urinary infections caused by ceftriaxone-resistant bacteria comparing with cefoperazone/sulbactam(2:1) on cefoperazone-resistant *** A total of 285 patients with respiratory or urinary tract infections were enrolled into this multicenter,open-label,randomized controlled clinical study,and the bacteria isolated from whom were either ceftriaxone-resistant or cefoperzaone-resistant. Two hundred fifty three patients completed the trial and 263 were enrolled into the ITT *** of the 285 patients were included into the safety *** patients were given ceftriaxone/sulbactam 2.5 g or cefoperazone/sulbactam 4.5 g twice daily,*** 7-14 days according to their *** trial was conducted at 8 medical centers in *** The cure and effective rates were 39.55%and 85.07%in the ceftriaxone/sulbactam group and 36.43%and 79.84%in the cefoperazone/sulbactam group,the bacterial eradication rates were 83.58%and 83.72%,and the adverse-event rates were 7.48%and 7.80%,*** were no significant differences between the two groups(P > 0.05).Conclusion Ceftriaxone/sulbactam is as effective and well-tolerated as cefoperazone/sulbactam for the treatment of intermediate and severe bacterial infections caused by resistant strains.

关键词： Resistant bacterial infection Ceftriaxone/sulbactam Randomized controlled clinical study

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