耐甲氧西林表皮葡萄球菌感染情况调查及药敏分析研究

目的 探讨耐甲氧西林表皮葡萄球菌的感染情况及其耐药性.方法 收集收集2013年7月至2016年4月住院患者的各类送检标本中分离鉴定的表皮葡萄球菌158株,由有经验的检验员采用BIOFOSUN微生物鉴定药敏分析系统对菌株进行鉴定,采用MIC法作抗生素敏感性试验,分析不同科室、不同年龄、不同标本及不同性别中MRSE菌株的分布情况;对院外与院内MRSE的临床特征进行分析;对MRSE在12种抗生素的药敏结果进行分析.结果 在表皮葡萄球菌感染的病例中耐甲氧西林表皮葡萄球菌(MRSE)占79.1％,且男性耐甲氧西林表皮葡萄球菌的检出率高于女性,>60岁的MRSE检出率高于30～60岁和<30岁的检出率,院内感染者检出率高于院外感染者,重症监护室MRSE的检出率为高于其他科室,来源于脓性分泌物标本的MRSE检出率高于血液标本和其他标本,差异均具有统计学意义(P<0.000).院内MRSE感染的患者中存在原发疾病的比例较院外感染的多,检出细菌前2周内服用两种以上抗生素的患者所占比例较院外感染的多,差异均具有统计学意义(P<0.05);MRSE对青霉素、氨苄西林、苯唑西林、头孢唑啉、红霉素及克林霉素的耐药性极强,均超过90.0％,而对环丙沙星、庆大霉素、四环素、利福平、甲氧苄啶/磺胺甲噁唑(SMZ)的耐药性较强,而对万古霉素敏感.结论 耐甲氧西林表皮葡萄球菌在临床上感染情况严重,且普遍存在对普通抗生素的耐药性.     

48株耐甲氧西林表皮葡萄球菌对7种头孢菌素的敏感性测定

采用琼脂稀释法对48株耐甲氧西林表皮葡萄球菌(methicillin-resistant Staphy-lococcus epidermidis,简称MRSE)进行了7种头孢菌素的敏感性测定,所有菌株对头孢呋肟和长效头孢菌素敏感(MIC90为8μg/ml),但对头孢氨苄、头孢唑林、头孢噻肟和ceftazidime则很少敏感(敏感菌株百分率分别为39.60％、22.9％、37.5％和35.4％)。所有MRSE对甲氧西林耐药(MIC_(90)>256μg/ml),而去甲万古霉素抗菌作用好。MRSE比MRSA的耐药性更高。     

3种鉴定耐甲氧西林葡萄球菌方法的比较

目的比较琼脂稀释、纸片及基因检测法鉴定甲氧西林耐药葡萄球菌的方法。方法按2004年美国临床实验室标准化委员会推荐的头孢西丁纸片扩散(K-B)法、琼脂二倍稀释(MIC)法,从中筛选出表型耐甲氧西林葡萄球菌(MRS),再将受试的葡萄球菌进行多重聚合酶链反应的体外扩增检测mecA基因。结果从临床分离的180株葡萄球菌中,mecA基因阳性葡萄球菌98株,其中金黄色葡萄球菌(SA)mecA基因阳性26株,阳性率为36.1%;凝固酶阴性葡萄球菌(CNS)mecA基因阳性72株,阳性率为66.7%,mecA阳性的MRS只对万古霉素、替考拉宁敏感。结论mecA基因的PCR检测能够尽早准确诊断,便于及时治疗MRS造成的感染。     

耐甲氧西林表皮葡萄球菌发生率及耐药性检测

目的 了解临床分离表皮葡萄球菌中耐甲氧西林菌株(MRSE)发生率及其耐药情况.方法 对128株表皮葡萄球菌进行头孢西丁纸片扩散法检测耐甲氧西林株,琼脂稀释法进行药敏试验.结果 128株表皮葡萄球菌中,MRSE检出率为79.7%.MRSE对多种抗菌药物耐药,对万古霉索、替考拉宁敏感,耐药率为0;除青霉素类、大环内酯类和糖肽类以外,MRSE对其他抗菌药物的耐药率均高于甲氧西林敏感表皮葡萄球菌(MSSE).结论 MRSE发生率高,耐多药,未发现糖肽类耐药株.     

49株表皮葡萄球菌的耐药分析

目的 分析从无菌体液标本中分离出的49株非重复表皮葡萄球菌对不同种类抗生素的耐药性,为临床合理用药提供参考.方法 收集临床分离出的49株非重复表皮葡萄球菌,用K-B法进行体外药敏试验,依据美国国家临床试验室标准化协会(CLSI)制定的标准判定药敏结果.结果 检出的49株非重复表皮葡萄球菌中耐甲氧西林表皮葡萄球菌(MRSE)的产生率达到83.7%.对头孢唑啉、亚胺培南和阿莫西林/克拉维酸的耐药率都在80%以上,对庆大霉素、环丙沙星、左氧氟沙星的耐药率在60%以上,对表皮葡萄球菌敏感率较高的有氯霉素、利福平、利奈唑胺、万古霉素,其中利奈唑胺和万古霉素均未出现耐药菌株.结论 表皮葡萄球菌的耐药情况严重,需加强表皮葡萄球菌的耐药监测,临床应结合药敏结果合理使用抗生素.     

肿痛安胶囊水提物对金黄色葡萄球菌和表皮葡萄球菌的体外抗菌活性

目的考察肿痛安胶囊水提物对金黄色葡萄球菌和表皮葡萄球菌的体外抗菌活性。方法采用琼脂二倍稀释法,以万古霉素为阳性对照品、以金黄色葡萄球菌ATCC29213为质控菌,测定了2个批次的肿痛安提取物对甲氧西林敏感金黄色葡萄球菌(MSSA)、耐甲氧西林金黄色葡萄球菌(MRSA)、甲氧西林敏感表皮葡萄球菌(MSSE)、耐甲氧西林表皮葡萄球菌(MRSE)共123株临床分离致病菌的最低抑菌浓度(MIC)。结果结果表明:肿痛安胶囊水提物对51株MRSA、25株MSSA、33株MRSE的MICrange为12.5 mg/ml~>50 mg/ml,MIC50分别为12.5 mg/ml、25 mg/ml、12.5 mg/ml;对受试的14株MSSE的MICrange为12.5~50 mg/ml,MIC50为25 mg/ml。结论肿痛安胶囊水提物对MRSA、MSSA、MRSE、MSSE均有较好的体外抗菌活性。     

盐酸万古霉素治疗新生儿MRSE/MRSA败血症35例临床研究

近年来,国内外报道革兰阳性球菌特别是耐甲氧西林表皮葡萄球菌(MRSE)/耐甲氧西林金黄色葡萄球菌(MRSA)在新生儿败血症的病原菌中呈增多趋势.据山西省儿童医院2003年1月至2004年5月统计结果,新生儿临床血标本的培养阳性者共148例,其中MRSE/MRSA35例,占23.65%,其中MRSE 29例,MRSA6例.由于MRSE/MRSA对青霉素类及多种头孢菌素耐药,因而为临床治疗带来了极大困难.万古霉素系治疗此类感染的首选药物,但其毒副作用一直为新生儿科医师所顾忌.盐酸万古霉素(稳可信,vancocin,美国礼来公司生产)作为万古霉素的新型制剂,在国内近年来应用越来越广泛.从2003年起,我们对新生儿MRSE/MRSA败血症进行了盐酸万古霉素疗效和安全性的临床观察,现报告如下.     

临床分离葡萄球菌耐药性和用药对策

目的了解葡萄球菌在临床感染中的情况及其对抗生素的耐药性,为抗生素的合理应用提供依据。方法采用苯唑西林纸片法(KB法)和自动化仪器法VITEK-32AMS系统GPI卡鉴定葡萄球菌,GPS-107卡鉴测耐苯唑西林的葡萄球菌(MRS)和β-内酰胺酶以及葡萄球菌的耐药谱。结果230株葡萄球菌中有72株金黄色葡萄球菌,其中耐苯唑西林(MRSA)的占73.6%,56株表皮葡萄球菌,其中耐苯唑西林(MRSE)的占66.07%,其它的102株凝固酶阴性的葡萄球菌中耐苯唑西林的占65.68%。其余的为对苯唑西林敏感的(MSS)菌株。结论临床分离的葡萄球菌中耐苯唑西林的葡萄球菌MRS占很大的比例,且对其它抗生素的敏感性明显低于对苯唑西林敏感的葡萄球菌。耐苯唑西林的葡萄球菌对万古霉素敏感性最高,利福平、呋喃妥因、复方磺胺甲口恶唑次之。     

万古霉素敏感性减低葡萄球菌筛选及抗生素耐药相关基因检测

目的 了解万古霉素敏感性减低葡萄球菌临床分离株对-内酰胺类、氨基糖苷类、四环素以及万古霉素耐药相关基因存在状况.方法 采用含61tg/mL万古霉素脑心浸液琼脂从临床分离的葡萄球菌中筛选万古霉素中介葡萄球菌和万古霉素耐药葡萄球菌;采用菌谱分析法筛选异质性万古霉素耐药葡萄球菌:E-test法和琼脂稀释法检测其MIC值;PCR技术扩增mecA,aac(6')/aph(2'),aph(3)-Ⅲ,tetM,vanA.vanB和vanC基因,并对阳性扩增产物进行测序.结果 从100株临床分离葡萄球菌中检出7株异质性万古霉素耐药葡萄球菌,并从部分菌株中检出耐药基因,mecA,aac(6')/aph(2'),aph(3')-川基因检出率分别为85.7%,57.1%和85.7%,没有检出tetM,vanA,vanB和vanC.对PCR阳性扩增产物进行测序,BLASTn比对分析,与已登录基因库的相同基因序列具有高度同源性.结论 同甲氧西林耐药葡萄球菌相似,万古霉素敏感性减低葡萄球菌携带多种耐药基因,耐药表型与基因分析支持该菌株多药耐药,该类菌株的检测对于指导临床合理用药具有积极意义.     

新生儿感染耐甲氧西林葡萄球菌的药敏分析

目的:探索致新生儿感染的耐甲氧西林葡萄球菌(MRS)流行病学及常见10种抗菌药物敏感性。方法:按《全国临床检验操作规程》鉴定细菌,玻片法血浆凝固酶试验,K－B扩散法药敏试验。结果:分离出葡萄球菌323株,其中金黄色葡萄球菌(SA)55株,耐甲氧西林金葡菌(MRSA)14株(25．5%),表皮葡萄球菌 171株,耐甲氧西林表葡菌(MRSE)102株(59,6%),腐生葡萄球菌97株,耐甲氧西林腐生葡菌(MRSS)52株(53．6%),院内感染株中 MRS所占比例明显高于甲氧西林敏感葡萄球菌(MS),x~2=3.978,P＝0.046。对氨苄西林、青霉素及红霉素总耐药率分别为86.8%、84.6%及68.9%,而对万古霉素及头孢唑啉总耐药率分别仅为6.7%(7/140)及11.3%(26/231),万古霉素对全部SA、甲氧西林敏感表葡菌(MSSE)、甲氧西林敏感腐生葡菌(MSSS)均敏感,MRS对青霉素、氨苄西林、头孢哇啉、头孢呋辛、头孢他啶、庆大霉素、阿米卡星、诺氟沙星及万古霉素的耐药率较MSS明显增高(P＜0.01)。结论:新生儿耐甲氧西林葡萄球菌易引起医院感染,其耐药性明显,值得高度重视．     

Clevudine University of Georgia/Abbott/Bukwang/Triangle/Yale University

The pyrimidine analog, clevudine (L-FMAU: 2'-fluoro-5-methyl-beta-L-arabinofuranosyluridine) is a potent antihepatitis B virus (HBV) and anti-Epstein-Barr virus (EBV) agent, discovered by researchers at the University of Georgia, in collaboration with Yale University and Bukwang. Bukwang transferred its technology to Triangle Pharmaceuticals in 1998 together with a license to develop clevudine worldwide except Korea [279649], [281942]. In June 1999, Triangle and Abbott Laboratories entered into a strategic alliance to copromote antiviral products including L-FMAU [326798]. In September 2000, Triangle Pharmaceuticals Inc initiated a 30-day phase I/II evaluation of clevudine in HBV-infected patients [381755]. Clevudine is a much less toxic derivative of the toxic agent P-D-FMAU. The mechanism of action of clevudine is not yet clear, but the agent induces a rapid decrease in HBV nucleic acid as doses increase from 0.3 to 10 mg/kg [319145]. It is believed that the target for clevudine lies in the viral replication mechanism. Clevudine is phosphorylated to the triphosphate form intracellularly. This is removed slowly from the cells, thus exerting a sustained inhibitory antiviral activity [178173], [320720], [320721].     

Spotlight from the American Society for Preventive Cardiology on Key Features of the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guidelines on the Management of Blood Cholesterol

The 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol retains focus on recommendations for statin treatment in the original four statin-eligible groups [those with atherosclerotic cardiovascular disease (ASCVD), diabetes, low-density lipoprotein cholesterol (LDL-C) ≥ 190 mg/dL, and higher risk primary prevention] without the use of treatment initiation or target LDL-C levels from the earlier 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline, but has several new features. First, patients with primary prevention are divided into those who are at low (< 5%), borderline (5% to < 7.5%), intermediate (7.5% to < 20%), and high (≥ 20%) risk based on the ASCVD risk estimator. Moreover, the new guideline goes further to consider a wider range of factors [now called “risk enhancers”—premature family history of ASCVD, persistently high LDL-C, chronic kidney disease (CKD), metabolic syndrome, conditions specific to women, inflammatory diseases, and high-risk ethnicities] that can be used to better inform the treatment decision. Moreover, more detailed recommendations on how the results of coronary calcium scanning can be used to inform the treatment decision are provided, including how it may be used to “de-risk” certain patients for delaying or avoiding the use of statin therapy. There are also specific sections for cholesterol management in other patient subgroups including women, children, certain ethnic groups, those with CKD, chronic inflammatory disorders and HIV, as well as discussion on the management of hypertriglyceridemia. Importantly, for persons with known ASCVD, a distinction is made for those who are at “very high risk” based on having had two major ASCVD events or one major event and two or more other high risk conditions, such as diabetes or other major risk factors, or bypass surgery or percutaneous intervention. Finally, the concept of a threshold LDL-C for initiating a non-statin therapy (after considering highest tolerated statin dosage) is provided, with ezetimibe recommended as the key non-statin to be added if the LDL-C still remains ≥ 70 mg/dL for all ASCVD patients, and in those who are at “very high risk”, further consideration for using a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. While the new guideline does have greater detail (and arguably, complexity), the refinements provide a strategy for guiding the clinician to target both statin and non-statin therapy to those most likely to derive benefit.     

Cerebral metabolism of [3H]-p-chloroamphetamine

The time-dependent metabolism of intraventricularly administered $\text{[}{}^3\text{H}\text{]-p-}\text{chloroamphetamine}$ was followed. The parent compound and its metabolites were recovered by high pressure liquid chromatography and characterized by high pressure liquid chromatography, thin-layer chromatography, and gas chromatography-mass spectrometry. By 4 hr after injection, two major toluene-soluble metabolites were present in brain. Their biological half-lives were different from the parent compound. On the basis of their analyses, one of the metabolites is p-chloronorephedrine, the other (P₃) is as yet unidentified. Pretreatment with Lilly 110140 prevented or markedly reduced the synthesis of both p-chloronorephedrine and P₃. Iprindole prevented the synthesis of p-chloronorephedrine. The P₃ appeared first in the brain then in the liver, suggesting that both of these organs can metabolize p-chloroamphetamine to this compound. The metabolites were recovered primarily from the nuclear and microsomal fractions following subcellular fractionation of the brain, with small quantities present in the synaptosomal fraction. The level of metabolites was higher in the brainstem than in the neocortex. Glutathione, administered simultaneously with p-chloroamphetamine either intraventricularly or intraperitoneally failed to alter the toxicity of p-chloroamphetamine.     

甘草配伍大戟的体外肝毒性研究

目的 研究甘草和大戟配伍的体外肝毒性。方法 采用显微观察法和MTT法检测不同浓度的甘草单煎液、大戟单煎液、甘草-大戟合煎液和甘草-大戟单煎混合液对人肝癌细胞HepG2增殖的影响,并比较大戟单煎液、甘草-大戟合煎液和甘草-大戟单煎混合液相当浓度下细胞毒性的大小。结果 大戟单用及大戟与甘草配伍均有细胞毒性,且呈剂量相关性;与大戟单煎液相比,甘草-大戟单煎混合液细胞毒性无明显差异,甘草-大戟合煎液细胞毒性减小。结论 甘草和大戟配伍导致大戟的体外肝毒性减小。     

Conversion of the N-O-glucuronide and N-O-sulfate conjugates of N-hydroxyphenacetin to reactive intermediates

The N-O-glucuronide of [¹⁴C]acetyl-N-hydroxyphenacetin is sufficiently stable to purify, but slowly breaks down in aqueous solutions to a reactive intermediate that can covalently bind to protein. When the pure compound was incubated in Tris buffer, pH 7.4, at 37°, it decomposed with a half-life of about 8.7 hr to the following compounds: phenacetin, 2-hydroxyphenacetin glucuronide, acetamide and acetaminophen. On addition of glulathione to the systems and allowing the reactions to go to completion, a glutathione-acetaminophen conjugate was formed at the expense of acetamide and acetaminophen: the fraction converted to phenacetin or to the 2-hydroxyphenacetin glucuronide was unchanged. On addition of ascorbic acid to the system and allowing the reactions to go to completion, the fraction converted to acetaminophen was increased at the expense of acetamide: the fractions converted to phenacetin and 2-hydroxyphenacetin glucuronide, however, were again unchanged. When the glucuronide was incubated with bovine serum albumin, covalent binding to the protein occurred at the expense of acetaminophen and acetamide; again, the fraction of the glucuronide converted to phenacetin and 2-hydroxyphenacetin glucuronide was unchanged. Moreover, the covalent binding could be partially prevented by addition of ascorbic acid or glutathione. Since there is formation of covalently bound material, the glutathione conjugate and acetaminophen appear to be interrelated; it seems likely that they are formed from a common intermediate, possibly acetylimidoquinone. However, the data suggest that the formation of phenacetin and 2-hydroxyphenacetin glucuronide occurs by different mechanisms. The N-O-sulfate of [¹⁴C]acetyl-N-hydroxyphenacetin also breaks down to a reactive intermediate that has properties similar to those of the reactive intermediate formed from the N-O-glucuronide and thus may also be N-acetylimidoquinone. By contrast, the relative ability of various nucleophiles to prevent the covalent binding of the reactive intermediate formed from the N-O-sulfate of 2-acetylaminofluorene to protein differs from the relative ability of the nucleophiles to prevent the covalent binding of the reactive intermediate of either the N-O-sulfate or the N-O-glucuronide of phenacetin, suggesting that the relative rates at which these intermediates combine with the different macromolecules may differ markedly.     

刺五加的研究进展

刺五加含有苷类、黄酮、多糖等多种活性成分,具有免疫调节、抗肿瘤、抗衰老、抗疲劳等药理作用。对国内外刺五加相关文献进行总结,为刺五加进一步的研究和开发提供参考资料。     

Structure-activity relationships of met5- and leus-enkephalin analogues

1. The effect of various analogues of met5- and leu5-enkephalin were determined on the reduction in twitch height of the electrically-stimulated longitudinal muscle preparation of the guinea-pig ileum and of the isolated mouse vas deferens. 2. In the guinea-pig ileum, D-alanine2-met5-enkephalin was the most potent whereas leu5-enkephalin was the most potent in the mouse vas deferens. 3. The met5-enkephalin analogues were more effective in reducing the twitch height of the ileum than they were in depressing that of the vas deferens preparation. The leu5-enkephalin analogues were more potent in their effects on the mouse vas deferens than they were on the guinea-pig ileum. 4. When a peptide bond is replaced by a glycol bond as in glycol2-3-leu5-enkephalin there is a marked reduction in opiate-like activity. 5. Substitution of a D-alanine residue for the glycine2 residue, as in D-alanine2-met5-enkephalin, increases the duration and potency of opiate-like activity. 6. These results confirm that modification of either met5- or leu5-enkephalin can alter the opiate-like potency of the resulting analogues. It appears that an intact tyrosyl residue of leu5-enkephalin is essential for such activity and that substitution of a D-alanine2 residue for the glycine2 residue confers resistance to enzymatic degradation on the met5-enkephalin peptide. In addition, the glycine2-3 peptide bond is essential for opiate-like activity.     

N6-苯甲酰基-2'-叔丁基二甲基硅氧基腺苷-3'-H-膦酸的合成工艺研究

目的 研究N~6-苯甲酰基-2′-叔丁基二甲基硅氧基腺苷-3′-H-膦酸的合成工艺。方法 以腺苷为起始原料,先对腺苷的嘌呤氨基进行苯甲酰基保护,再分别向腺苷的5′位和2′位引入二甲氧基三苯甲基(DMT)和叔丁基二甲基硅基(TBDMS)保护基,制备得到关键中间体N~6-苯甲酰基-5′-二甲氧基三苯甲氧基-2′-叔丁基二甲基硅氧基腺苷(3)。中间体3与磷试剂2-氯-4H-1,3,2-苯并二氧磷杂环己烷-4-酮反应引入膦酸基团,最后使用二氯乙酸脱除DMT保护基得到目标产物。结果 经过5步反应得到了目标化合物N~6-苯甲酰基-2′-叔丁基二甲基硅氧基腺苷-3′-H-膦酸,并利用~1H-NMR、~(31)P-NMR、质谱等方法确证了其结构。本合成工艺的总收率为35.7%,目标化合物的质量分数为98.5%。结论 该合成工艺与原有方法相比步骤短,操作简单,具有良好的应用前景。     

Nampt/Visfatin/PBEF研究进展

尼克酰胺磷酸核糖转移酶(nicotinamide phosphoribosyltransferase,Nampt)是生物合成NAD的关键限速酶,又被称为前B细胞克隆增强因子(pre-B cell colony enhancing factor,PBEF)和内脏脂肪素(visfatin).最近研究发现,Nampt/Visfatin/PBEF在NAD生物合成、代谢、炎症反应和细胞增殖、分化、凋亡等诸多领域发挥作用,可能影响2型糖尿病、急性肺损伤、恶性肿瘤等疾病发生、发展和预后.本文主要对Nampt/Visfatin/PBEF的生理功能及临床意义进行综述.     

Quantitative histochemical studies of striatal dopamine depletion following dl-α-methyl-p-tyrosine administration

This study investigated the use of a microfluorimetric histochemical method for the measurement of the depletion of dopamine in the rat caudate nucleus, following α-methyl-p-tyrosine (α-MT) administration. The depletion in three behavioral situations was compared with that of a control group which remained in a cage.The results of the control group indicate that there had been a reduction of approximately 50% in the intensity of the formaldehyde-induced fluorescence derived from dopamine in a region of the neuropil of the caudate nucleus, during the interval (3 hr 40 min) between α-MT, 300 mg/kg i.p., and killing. Disruption of conditioned avoidance response (CAR) performance after α-MT administration was confirmed, but in this study CAR performance in previously trained rats did not have a significant effect on the depletion of formaldehyde-induced fluorescence of the striatal neuropil after α-MT administration. The levels of α-MT-induced depletion of formaldehyde-induced fluorescence in the striatal neuropil following a period of muscular co-ordination/activity and following a period of CAR training were also not significantly different from those shown by a control group.