糖肽类抗菌药物利用评价标准的建立与应用分析

目的 建立糖苷类抗菌药物（万古霉素和替考拉宁）的药物利用评价标准,并评价糖肽类抗菌药物临床用药情况。方法 以药品说明书为基础,参照相关规范和专家共识,建立万古霉素和替考拉宁药物利用评价标准;采用回顾性研究方法,对2017年1月-6月274例使用万古霉素和替考拉宁的病例进行合理性评价。结果 糖肽类抗菌药物治疗有效率为75.91%,用药指征符合率为92.70%,剂量正确率为98.18%,用法正确率为91.24%,疗程合理率为79.93%,联合用药合理率为72.26%。结论 建立的万古霉素和替考拉宁药物利用评价标准可用于规范糖肽类抗菌药物的使用,该院万古霉素和替考拉宁的使用基本合理。     

2017年福州市第二医院病原菌的分布及耐药性分析

目的 了解2017年福州市第二医院临床分离病原菌的分布及对抗菌药物的敏感性,为临床用药提供指导。方法 共收集2 720株非重复分离菌,采用纸片扩散法或自动化仪器法进行药敏试验,按CLSI标准判读药敏结果。结果 2 720株细菌中,标本主要来源于伤口分泌物（989株）,占36.3%。革兰阴性菌1 786株,占65.7%,主要为大肠埃希菌、肺炎克雷伯菌、铜绿假单胞菌、鲍曼不动杆菌、嗜麦芽窄食单胞菌和阴沟肠杆菌;革兰阳性菌934株,占34.3%,主要为金黄色葡萄球菌、粪肠球菌和凝固酶阴性葡萄球菌。耐甲氧西林耐药株金黄色葡萄球菌、凝固酶阴性葡萄球菌的检出率分别为42.7%、84.2%。未发现对万古霉素、替考拉宁和利奈唑胺耐药的葡萄球菌。粪肠球菌对大多数抗菌药物的耐药率明显低于屎肠球菌。肠球菌属中未发现万古霉素、利奈唑胺、替考拉宁耐药的肠球菌。除对黏菌素100%敏感外,铜绿假单胞菌对其他常见抗菌药物的耐药率均较低,鲍曼不动杆菌除对黏菌素敏感外,对其他药物的耐药性均较高,均达46.2%以上。结论 2017年福州市第二医院病原菌耐药形势依旧严峻,应加强合理用药,避免交叉感染。     

2014—2017年六安市人民医院住院患者抗菌药物使用情况分析

目的 分析2014—2017年六安市人民医院住院患者抗菌药物的使用情况。方法 调取2014—2017年六安市人民医院抗菌药物的相关用药信息,并从多个角度对抗菌药物的使用率、使用强度（AUD）、用药频度（DDDs）、日均费用（DDC）进行回顾性统计分析。结果 抗菌药物给药途径以静脉注射为主,2014—2017年,抗菌药物使用率和AUD均下降,但各类品种选择结构有明显变化。总体上β-内酰胺类药物选用比例有所下降,但在住院患者抗菌药物中β-内酰胺类药物仍然DDDs及占比最高。第1、3、4代头孢的DDDs总体呈波动式下滑的趋势,只有第2代头孢的DDDs总体上呈上升的趋势,由于第3、4代头孢DDDs占比较少,第2代头孢取代第1代头孢的趋势比较明显,第2代头孢中头孢呋辛有取代头孢替安的趋势。β内酰胺/β内酰胺酶抑制剂复方制剂中哌拉西林他唑巴坦大幅增长,头孢哌酮钠舒巴坦钠、阿莫西林克拉维酸钾大幅下降。碳青霉烯类和头霉素类出现明显增长。单环β内酰胺类氨曲南的DDDs出现大幅下降。氟喹诺酮类药物中的盐酸莫西沙星氯化钠注射液、大环内酯类中的阿奇霉素干混悬剂逐年增长较为迅速,抗真菌药物伏立康唑（国产）、替考拉宁和利奈唑胺DDDs均显著增加。结论 2014—2017年六安市人民医院抗菌药物的管理是有效的,但应注意品种结构选择的变化及抗菌药物销售金额的增长,尤其关注哌拉西林他唑巴坦、头孢西丁钠、莫西沙星、比阿培南、伏立康唑、替考拉宁、利奈唑胺的不合理用药问题。     

2010~2012年长江流域抗MRSA药物利用分析

回顾分析2010~2012年长江流域抗MRSA药物应用状况及趋势。该类药物用药总金额逐年上升,其中糖肽类药物使用金额所占比重最大;通用名金额排序中万古霉素超越替考拉宁,位列第一;DDDs排序位于前列的有糖肽类和利奈唑胺。     

我院抗菌药使用与葡萄球菌耐药率变化的相关性分析

摘 要 目的:对南京医科大学第二附属医院抗菌药使用情况和葡萄球菌属的耐药情况进行统计分析,为临床合理使用抗菌药提供参考依据。方法：对我院2010～2012年抗菌药的用药频度（DDDs）及所分离的葡萄球菌属的药敏结果分别进行统计分析。结果：2010～2012年我院抗菌药的DDDs分别为357 978.3,379 699.9和264 053.4。3年共分离葡萄球菌3 228株,未发现耐万古霉素、利奈唑胺菌株,出现了少数替考拉宁耐药菌株。3年来葡萄球菌属的耐药率总体呈下降趋势,金黄色葡萄球菌对万古霉素、替考拉宁、利奈唑胺、呋喃妥因的耐药率在0～0.93%之间,略低于凝固酶阴性葡萄球菌的耐药率（0～2.3%）,仍高度敏感;凝固酶阴性葡萄球菌对红霉素、左氧氟沙星、苯唑西林、复方磺胺甲噁唑耐药率分别为79.8%,58.8%,72.8%,44.1%,高于金黄色葡萄球菌对这四种药的耐药率60.8%,42.1%,60.0%,26.2%。金黄色葡萄球菌对呋喃妥因和替考拉宁的耐药率与头孢菌素类药DDDs呈正相关;凝固酶阴性葡萄球菌对庆大霉素耐药率与大环内酯类药DDDs,对米诺环素耐药率与青霉素类药DDDs、氨基糖苷类药DDDs,对利福平耐药率与糖肽类药DDDs之间,对苯唑西林耐药率与硝基咪唑类药DDDs均呈正相关。结论：3年来葡萄球菌属的耐药率虽然有所波动,但总体呈下降趋势,与抗菌药的使用减少有一定的关系。     

3种药物治疗耐甲氧西林金黄色葡萄球菌感染的疗效及其相关因素分析

摘 要 目的：评价万古霉素、替考拉宁及利奈唑胺治疗耐甲氧西林金黄色葡萄球菌（MRSA）感染的疗效、安全性及相关影响因素。 方法：采用回顾性研究方法,收集某三甲医院2016 年8月～2017 年 1月使用万古霉素、替考拉宁及利奈唑胺治疗MRSA感染的病例,统计不同用药组患者的年龄、性别、感染部位、病原学检查、用药情况、药品不良反应等,评价比较3组疗效。结果：共纳入260例患者,主要是中老年患者,感染部位主要分布在肺部、腹腔、颅内、皮肤软组织及血液。万古霉素组（100例）、替考拉宁组（80例）、利奈唑胺组（80例）临床有效率分别为68.00%,70.00%,73.75%,差异无统计学意义（P＞0.05）;药品不良反应发生率分别是23.00%,7.50%,30.00%,替考拉宁组与万古霉素组、利奈唑胺组相比,差异有统计学意义（P<0.01）;万古霉素组发生肾功能损害16例,利奈唑胺组发生血小板减少16例。〖HTH〗结论：〖HTK〗3组药物有效率不高可能分别与感染部位用药选择、血药浓度监测较少、不良反应发生、首剂负荷剂量不足、合并感染等多种因素有关,临床治疗应加以重视。     

利奈唑胺对临床分离阳性球菌的体外敏感性分析

目的:对比利奈唑胺与万古霉素及其他几种常用抗菌药物对临床分离阳性球菌的体外抗菌活性。方法:按照NCCLS(CLSI)2007纸片扩散法操作标准测定利奈唑胺与其他几种常用抗菌药物的体外抗菌活性。结果:本院分离的耐甲氧西林金黄色葡萄球菌(MRSA)比例较高(79.1%),利奈唑胺、万古霉素、替考拉宁的敏感率均达到100%。耐甲氧西林凝固酶阴性葡萄球菌(MRC-NS)的比例较MRSA高(88.9%),利奈唑胺与万古霉素、替考拉宁活性相当,敏感率均为100%。利奈唑胺对粪肠球菌的活性与万古霉素、替考拉宁相当,对屎肠球菌的活性优于万古霉素和替考拉宁(100%,80.4%,78.1%),对青霉素耐药的肺炎链球菌(PRSP)也表现了优越的抗菌活性。结论:对于MRSA、MRCNS、PRSP、粪肠球菌,利奈唑胺与万古霉素、替考拉宁的活性相当,均为100%的敏感率;对屎肠球菌的抗菌活性优于万古霉素和替考拉宁,是治疗多药耐药阳性球菌感染的新型药物。     

耐甲氧西林金黄色葡萄球菌耐药分析

目的了解全院临床科室耐甲氧西林金黄色葡萄球菌(MRSA)耐药情况,为呼吸科临床治疗提供抗菌药选用依据。方法对临床分离的28株金黄色葡萄球菌中耐甲氧西林金黄色葡萄球菌(MRSA)的药物敏感报告单进行耐药分析。结果 28株金黄色葡萄球菌中耐甲氧西林金黄色葡萄球菌(MRSA)的检出率为53.57%,MRSA对18种抗菌药物中种耐药率>63.24%,对青霉素类、头孢菌素类以及红霉素100.0%耐药,MRSA对替考拉宁、利奈唑胺100.0%敏感,检测到1株耐万古霉素金黄色葡萄球菌。结论本研究中我院呼吸科MRSA发生率低于国内平均水平,复方新诺明和氯霉素对其仍较敏感,万古霉素出现耐药菌株,替考拉宁、利奈唑胺仍为首选。     

利奈唑胺、替考拉宁和万古霉素等抗菌药物对常见需氧革兰阳性球菌的体外抗菌活性

目的评价利奈唑胺、替考拉宁和万古霉素等抗菌药物的体外抗菌活性。方法采用琼脂稀释法对临床收集的132株革兰阳性球菌进行抗菌活性测定,记录其各自的MIC并进行比较。结果利奈唑胺、替考拉宁及万古霉素3药对革兰阳性球菌均有较大抗菌活性,敏感率均为100%,包括其中的耐甲氧西林葡萄球菌和青霉素中介肺炎链球菌均有良好抗菌作用。3药在部分革兰阳性球菌的抗菌作用中与利福平相仿,但比氨基糖苷类抗生素和氟喹诺酮类抗菌药强。在对甲氧西林敏感金葡萄的抗菌活性中,替考拉宁的MIC90均为利奈唑胺和万古霉素的4倍;在对甲氧西林敏感凝固酶阴性葡萄球菌的抗菌活性中,替考拉宁的MIC90分别均为利奈唑胺和万古霉素的8倍;而在青霉素敏感和中介肺炎链球菌的抗菌活性中,替考拉宁的MIC90为利奈唑胺的1/16,为万古霉素的1/8;在肠球菌属的抗菌活性中,万古霉素的MIC90分别为利奈唑胺的2倍,是替考拉宁的4倍和8倍。结论利奈唑胺、替考拉宁以及万古霉素等三药对革兰阳性球菌有较大的抗菌作用,对部分革兰阳性菌的抗菌作用与利福平相仿,但比其他如氨基糖苷类抗生素和氟诺酮类抗菌药更优,是临床革兰阳性球菌严重感染的有效药物。     

老年科常用抗菌药物与药敏情况分析

目的：分析老年科常用抗菌药物与药敏情况。方法：收集2020年6月—2021年6月我院老年科382例住院患者的病历资料、样本培养结果,分析病原菌分布及药敏情况。结果：382例患者中感染部位为呼吸系统的患者占比最高,为42.36%。样本培养共分离出致病菌221株,其中革兰阳性菌49株,革兰阴性菌132株,真菌40株。金黄色葡萄球菌对阿米卡星、利奈唑胺、呋喃妥因、利福平、替考拉宁、四环素、万古霉素的敏感性均达90%以上。溶血葡萄球菌对利奈唑胺、呋喃妥因、利福平、替考拉宁、万古霉素的敏感性均为100.0%。粪肠球菌对利奈唑胺、万古霉素的敏感性达80%以上。肺炎克雷伯菌对哌拉西林、氨苯西林的敏感性均为100.0%。大肠埃希菌对氨苯西林的敏感性较高,为80.0%。铜绿假单胞菌、鲍曼不动杆菌对头孢替坦、呋喃妥因、头孢曲松、氨苯西林的敏感性均为100.0%。结论：对常用抗菌药物的药敏情况进行研究,可为医院抗菌药物的管理提供依据。     

Elimination of various polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) in rat faeces

A defined mixture (of a composition characteristic of that present in incinerator fly ash) of polychlorinated dibenzo-p-dioxins and -furans (PCDDs and PCDFs) was subcutaneously administered to rats and the elimination of the unchanged congeners via faeces was measured. 1) All congeners administered could be found in faeces. 2) The rates of elimination via faeces were rather different for the different congeners. 3) The most toxic congeners, 2378-T4CDD and 12378-P5CDD, were present in unmetabolized form in faeces to < 4% and < 8% of the administered dose within the first week. Thus, parenteral administration clearly minimizes contamination of the animal quarters when compared with corresponding oral dosing. 4) The rate of unchanged elimination was apparently especially pronounced for the higher chlorinated PCDDs and PCDFs. The highest excretion rate was found for 1234678-H7CDD (up to 30% of administered dose). 5) No obvious differences were observed in the rates of elimination of the unchanged substances via faeces of the 2378-substituted or the non-2378-substituted isomers.Abbreviations Used PCDDs PCDFs polychlorinated dibenzo-p-dioxins, and -furans - T4CDDs T4CDFs tetra-chlorinated dibenzo-p-dioxins, and -furans - P5CDDs P5CDFs penta-chlorinated dibenzo-p-dioxins, and -furans - H6CDDs H6CDFs hexa-chlorinated dibenzo-p-dioxins, and -furans - H7CDDs H7CDFs hepta-chlorinated dibenzo-p-dioxins, and -furans - OCDD OCDF octa-chlorinated dibenzo-p-dioxin, and-furan - DMSO dimethyl-sulfoxide     

Pharmacokinetic and Metabolic Disposition of p-Chloro-m-xylenol (PCMX) in Dogs

The pharmacokinetic and metabolic profile of p-chloro-m-xylenol (PCMX) was studied in healthy mongrel dogs after intravenous and oral administration of single doses of 200 and 2000 mg of PCMX, respectively. Calculation of pharmacokinetic parameters was based on compartmental and noncompartmental methods. The mean pharmacokinetic parameters of elimination half-life and mean residence time were 1.84 and 1.69 hr, respectively. The apparent volume of distribution at steady state was estimated to be 22.4 liters, and the plasma clearance was 14.6 liters/hr. The bioavailability of PCMX was 21%, indicating low absorption for this drug. PCMX's metabolite data show that a presystemic elimination process (first-pass effect) is also occurring. PCMX plasma concentrations after intravenous administration of 500-, 200-, and 100-mg doses were found to be proportional to the dose given, demonstrating that the pharmacokinetic profile of PCMX is linear over the dose range studied. Biotransformation studies showed that urinary excretion was not the major route for rapid elimination of unchanged PCMX and almost all material excreted in urine was associated with the conjugated species (glucuronides and sulfates). Statistical significant differences were not found (P > 0.05) between the percentages excreted in urine of PCMX and its conjugated metabolites after intravenous and oral administration. The percentages excreted in urine after iv and oral doses of unchanged PCMX were, respectively, 0.45 and 0.37; total conjugates, 46.3 and 43.3; sulfates, 38.1 and 33.2; and glucuronides, 8.2 and 10.2.     

特征肽技术用于龟甲(浙龟甲)中掺巴西龟的检查研究

目的 找出巴西龟特征肽段,建立龟甲（浙龟甲）中掺入巴西龟的专属性检查方法。方法 样品以水提法提取,胰蛋白酶酶解,利用超高效液相色谱-四级杆飞行时间质谱和数据处理软件查找巴西龟特征肽,并利用蛋白质搜库技术初步测序;利用找到的特征肽段,建立超高效液相色谱-串联四级杆质谱的多反应监测的巴西龟掺伪专属性检查方法。结果 找出巴西龟特征性肽段m/z 400.23（双电荷）,并初步测定序列,通过分析该特征肽段二级质谱图,确定了专属性检测离子对m/z 400.23（双电荷）→374.05,142.90,并建立了龟甲（浙龟甲）中掺入巴西龟的专属性检查方法。20批样品中,11批样品检出巴西龟成分。结论 该方法的专属性强,符合分析检测的方法技术要求,可用于龟甲（浙龟甲）掺入巴西龟的检查。     

Pharmacological characterization of N-methyl-D-Aspartate receptors in spinal cord of rats with a chronic peripheral mononeuropathy

N-Methyl-D-aspartate (NMDA) receptor antagonists, acting in the spinal cord, are analgesic. However, the clinical utility of these antagonists is diminished by their adverse effects on cognition and behavior. To facilitate the development of spinal cord-selective NMDA receptor antagonists, we characterized ligand interactions at NMDA receptors in spinal cord of normal rats and rats with a chronic peripheral neuropathy. NMDA receptors in spinal cord were distinguished from those in cerebral cortex on the basis of differences in the potencies of competitive and noncompetitive antagonists and on the basis of differences in their response to spermidine. D(-)-2-Amino-5-phosphonopentanoic acid (AP-5) and (+)-(1-hydroxy-3-aminopyrrolidine-2-one) (HA-966) were more potent in inhibiting NMDA-dependent [³H]TCP binding in spinal cord while, conversely, MK-801 was more potent in inhibiting [³H]TCP binding to NMDA receptors in cerebral cortex. Spermidine increased [³H]TCP binding to NMDA receptors in cerebral cortex (39 ± 8%) but not spinal cord (2 ± 1%). Based on these properties, NMDA receptors in spinal cord more closely resembled those in cerebellum than those in cerebral cortex. Generation of a chronic neuropathy had no effect on the density of NMDA receptors in lumbar spinal cord. There were also no major changes in the potencies of competitive antagonists or channel blocking ligands, although there was a trend for kynurenic acid and -CPP to be more potent in the spinal cords of neuropathic animals. These findings indicate that, in both normal and neuropathic pain states, NMDA receptors in spinal cord can be distinguished pharmacologically from those in cerebral cortex. These findings underscore the feasibility of developing spinal cord-selective NMDA receptor antagonists as novel analgesics.     

Relevance and analysis of traffic related platinum group metals (Pt,Pd, Rh) in the aquatic biosphere,with emphasis on palladium

Following the introduction of automobile catalysts in the middle of the Eighties in Germany there is an increasing emission of the platinum-group-metals (PGM) platinum (Pt), palladium (Pd) and rhodium (Rh). Still, it remains unclear if these metals are bioavailable for aquatic animals and to which extent they accumulate in the aquatic biosphere. Zebra mussels (Dreissena polymorpha ) were maintained in water containing road dust at a concentration of 1 kg/10 l. Following an exposure period of 26 weeks, soft tissues of the mussels were analysed applying adsorptive cathodic stripping voltammetry (ACSV) for the determination of Pt and Rh and total-reflection X-ray fluorescence analysis after co-precipitation of Pd with mercury. This experiment revealed for the first time that all the three catalyst emitted metals were accumulated by mussels. The bioaccumulation increased in the following manner: Rh相似文献   

Serum unconjugated bisphenol A concentrations in men may influence embryo quality indicators during in vitro fertilization

Here we assess bisphenol A (BPA) in couples undergoing in vitro fertilization (IVF) and indicators of embryo quality; embryo cell number (ECN) and embryo fragmentation score (EFS). Twenty-seven couples provided serum on the day of oocyte retrieval. Unconjugated BPA was measured by HPLC with Coularray detection. Odds ratios (OR) were generated using ordinal logistic regression including female and male BPA concentrations, age and race, and day of embryo transfer for ECN. Inverse associations are suggested for male BPA with ECN (OR = 0.70, P = 0.069), and EFS (OR = 0.54, P = 0.009), but not for women. Male BPA exposure may affect embryo quality during IVF.     

In vitro study of lysozyme in poly(lactide-co-glycolide) microspheres with sucrose acetate isobutyrate

This study investigated the suitability of microsphere formulations for extended protein delivery and complete protein release. These microspheres were prepared by a multi-emulsion method and prepared using a mixture of poly(lactide-co-glycolide) (PLGA), RG 502H (lactide:glycolide=50:50, M(W) 9300) and sucrose acetate isobutyrate (SAIB). SAIB embedded into the microspheres and mixed with PLGA, improved the efficiency of enzyme encapsulation. The in vitro release rate of lysozyme (Lys) from the microspheres was reduced due to the high viscosity of the added SAIB and less degradation of PLGA by SAIB. These properties enabled prolonged release of Lys for up to 2 months, characterized by a minimal initial burst of Lys and nearly zero-order protein release kinetics result from co-administration of sorbitan monooleate 80. When it is considered that degradation products of SAIB are inactive for labile proteins, SAIB may be regarded as a promising candidate for long-acting protein delivery.     

Anti-erbB-2 antibody trastuzumab in the treatment of HER2-amplified breast cancer

Human epidermal growth factor receptor-2 (HER2/erbB-2) is a member of a family of four transmembrane receptor tyrosine kinases that regulate cell growth, survival and differentiation via multiple signal transduction pathways. Amplification of the HER2 gene occurs in 20–25% of human breast cancers. This amplification event is an independent adverse prognostic factor as well as a predictive factor for increased response to doxorubicin-based combination chemotherapy, response to trastuzumab and decreased response to hormonal therapy. Methods for detecting protein overexpression or gene amplification in clinical tumor specimens include immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) techniques, with the latter considered by some to be more accurate. Trastuzumab (Herceptin) is a recombinant humanized monoclonal antibody which targets an epitope in the extracellular domain of the HER2 protein. Preclinical models demonstrated that this antibody has significant anti-tumor activity as a single agent and has synergy with certain chemotherapeutic drugs. Phase II and III clinical trials performed in women with metastatic breast cancer that overexpress HER2 have shown that trastuzumab has clinical activity when used as first-, second- or third-line monotherapy, and improves survival when used as first-line therapy in combination with chemotherapy. Newer combinations with numerous chemotherapeutic drugs have also shown significant clinical activity in phase II studies. In all of these trials, trastuzumab was generally well-tolerated, but cardiac toxicity (particularly when the antibody was combined with anthracyclines) was an unexpected adverse effect. Although trastuzumab is currently usually administered on a weekly intravenous schedule, evidence suggests that a triple dose of the drug given once every three weeks has a pharmacokinetic profile expected to be equally efficacious. Neither the optimal schedule nor the optimal duration of trastuzumab therapy has yet been clearly defined in controlled clinical trials. Current clinical investigations of trastuzumab include its use in both the adjuvant and neoadjuvant settings as well as in combination with other chemotherapy drugs or new biologic targeted agents.     

The Cytotoxicity of p-Chloro-m-xylenol in Primary Culture of Rat Hepatocytes

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