治疗耐甲氧西林金黄色葡萄球菌感染的抗体药物

耐甲氧西林金黄色葡萄球菌(methicillin-resistant staphylococcus aureus, MRSA) 作为超级细菌的典型代表,严重威胁人民群众的健康。目前经典的抗生素治疗和疫苗主动预防都无法有效控制MRSA的感染。近年来,随着抗体药物产业的兴起,诸多药物研发公司和研究人员致力于研究治疗性抗体,以期控制MRSA的感染并已经取得了很多突破。就治疗MRSA感染的抗体药物研究进展作一简要综述。     

耐药机制指导下的抗金葡菌药物开发现状

金黄色葡萄球菌是全球院内感染的首要病原菌,临床分离的金葡菌80%以上为耐甲氧西林(MRSA)菌株,因其耐药性,尤其是多重耐药性的快速增长,抗MRSA感染日益成为抗感染治疗的难点和热点。近年来,人们在充分认识金葡菌耐药机制的基础上,积极开发新型抗MRSA药物,取得了长足发展。对MRSA的耐药机制及该机制指导下抗金葡菌药物开发现状作一综述。     

科研快讯

《自然-化学生物学》:混合使用抗生素新方法问世感染性细菌的药物抗性日渐增加,迫使科学家们发明新方法来对付这些有害细菌。现在,通过将现有抗生素与非抗生素药物混合使用,研究人员发现了一种重新使用抗生素药物的新方法,新成果发表在4月在线出版的《自然-化学生物学》期刊上。Eric Brown、Gerard Wright和同事合作,将治疗帕金森氏症、癌症、炎症和其他疾病的药物与抗生素共同使用,试图寻找混合药物比单个药物效果更好的病例。他们鉴别出非抗生素药物能弱化细菌细胞的几种病例,从而让现有的抗生素能杀死这些细菌。洛派丁胺是一种治疗腹泻的药     

美国微生物学会杂志摘要

1．Hibbard提出了一个可以讨论的问题：“如果在感染初期采用联合抗微生物治疗，人类是否可以控制微生物感染？”支持这一观点的理由为：①当抗微生物药物的作用机制不同，同时采用2～3种抗微生物制剂将可减少微生物因突变而同时出现对数种药物耐药的菌株；②联合使用抗生素后，可在病人血清中出现杀死微生物的浓度；③近来临床采用局部联合消毒剂，较单用一种消毒剂更有效，而并未增加其不良反应；     

《PLoS综合》：研究解析雷公藤分子作用机制

从天然产物中寻找抗肿瘤活性成分是发展抗肿瘤药物的重要策略之一,雷公藤是我国一种资源比较丰富的传统中草药,其结构多样的有效成分具有明显的抗炎、免疫抑制和抗肿瘤等作用,是开发治疗药物的一个宝藏,但雷公藤具有很大的毒性,分子靶点和作用机制不清楚,是迄今制约雷公藤发展成真正治疗药物的关键。     

069人工接种棒状杆菌消除定植鼻腔的金黄色葡萄球菌

近年耐甲氧西林金黄色葡萄球菌(MRSA)检出率在全球范围内正逐年升高.危重病人鼻腔内携带MRSA是引起继发感染的重要危险因素,有效地消除鼻腔中携带的MRSA可预防医院内感染.通常要消除MRSA感染,临床选用万古霉素、莫匹罗星等强抗生素,但这类抗生素可引起机体肝、肾功能严重损害而限制其实际使用.因此,人们试图寻找一种非抗生素的生物法,维护鼻腔内微生态环境以消除金黄色葡萄球菌.     

美国微生物学会杂志摘要

1.Hibbard提出了一个可以讨论的问题:"如果在感染初期采用联合抗微生物治疗,人类是否可以控制微生物感染?"支持这一观点的理由为:①当抗微生物药物的作用机制不同,同时采用2～3种抗微生物制剂将可减少微生物因突变而同时出现对数种药物耐药的菌株;②联合使用抗生素后,可在病人血清中出现杀死微生物的浓度;③近来临床采用局部联合消毒剂,较单用一种消毒剂更有效,而并未增加其不良反应;④基因转录的图谱显示如表达过多的抗性基因,微生物的一些重要基因产物将被上调;⑤如果某种抗生素的药物动态学显示互相之间并无拮抗作用,联合使用抗菌药物可缩短疗程.作者认为联合使用的抗菌药物应分别具有不同作用机制,方有价值,但是经济问题应做深入研究以作全面考虑.     

中药治疗骨质疏松症的现状及展望

采用西药治疗骨质疏松症存在着毒性大、价格昂贵等问题,迄今为止还没一个有效且毒副作用小的骨质疏松症治疗药物。中国古代本草书籍中记载着大量对骨科疾患有疗效的中草药,积累了大量的临床经验。从中草药中寻找抗骨质疏松症药物成为研究热点课题,在中医理论指导下开发此类中药是切实可行的。     

中草药治疗牙周病

牙周病是严重危害口腔健康的常见病。临床上多是以机械洁治后辅以抗菌药治疗。当前辅助的治疗药物多以抗生素类药物为主,但此类药物不仅破坏菌群平衡,还会使致病菌产生耐药性。中草药生物活性广泛、安全性高,利用其抑菌、抗炎、增加免疫、促进组织修复等功能治疗牙周病日益引起人们关注。本文对中草药治疗牙周病展开综述,为中草药的合理用药提供理论基础。     

动物乳腺生物反应器 一种神奇的制药方式

正人吃五谷杂粮,难免会生病,因此我们的生活离不开医药产业。纵观人类药物发展的历史,经历了三个不同的发展阶段。最初是天然药物,主要是利用中草药或提取中草药中的活性成分加工成中成药,用于疾病的治疗和预防。在这方面,我国中草药为世界医药的发展做出了巨大贡献,拥有绝对的发言权。随着西方科技的发展,化学药物渐成主流,药物合成逐渐兴起,与第一代药物相比,其活性更高、更有效。现在我们广泛使用的各类抗生素大部分属于这一类药物。20世     

Modeling methicillin-resistant Staphylococcus aureus in hospitals: Transmission dynamics, antibiotic usage and its history

ABSTRACT: Methicillin-resistant Staphylococcus aureus (MRSA) infection has been prevalent in many hospitals worldwide. To investigate the transmission dynamics of MRSA and how certain factors influence the prevalence of MRSA infection when antibiotics are given to patients to treat or prevent bacteria infections either from MRSA itself or other pathogens, mathematical modeling was used. Our results suggest that: (i) MRSA always persists in the hospital when there is admission of colonized and infectious patients; (ii) the longer duration of treatment in infectious patients, the less probability of a successful treatment, the longer duration of contamination in health care workers (HCWs), and the higher number of required contacts of patients may lead to the higher prevalence of MRSA infection; (iii) in an attempt to control the prevalence of MRSA infection, the possible ways are to treat patients with antibiotic exposure as quickly and efficiently as possible, and to screen, isolate, and decolonize colonized and infectious patients at admission; (iv) in addition, other strategies such as using antimicrobial susceptibility tests to help treating patients with MRSA infection with the right antibiotics, constantly developing novel drugs, and strict hand-washing of HCWs, for example, may also help to reduce the prevalence of MRSA infection.     

Anti‐infectious activity of synbiotics in a novel mouse model of methicillin‐resistant Staphylococcus aureus infection

The anti‐infectious activity of synbiotics against methicillin‐resistant Staphylococcus aureus (MRSA) infection was evaluated using a novel lethal mouse model. Groups of 12 mice treated with multiple antibiotics were infected orally with a clinical isolate of MRSA at an inoculum of 10⁸ CFU on day 7 after starting the antibiotics. A dose of 400 mg/kg 5‐fluorouracil (5‐FU) was injected intraperitoneally on day 7 after the infection. A dose of 10⁸ CFU Bifidobacterium breve strain Yakult and 10 mg of galactooligosaccharides (GOS) were given orally to mice daily with the antibiotic treatment until day 28. The intestinal population levels of MRSA in the mice on multiple antibiotics were maintained stably at 10⁸ CFU/g of intestinal contents after oral MRSA infection and the subsequent 5‐FU treatment killed all the mice in the group within 14 days. B. breve administration saved most of the mice, but the synbiotic treatment saved all of the mice from lethal MRSA infection. The synbiotic treatment was effective for the treatment of intestinal infection caused by four MRSA strains with different toxin productions. There was a large difference among the six Bifidobacteria strains that were naturally resistant to the antibacterial drugs used. B. breve in combination with GOS is demonstrated to have valuable preventive and curative effects against even fatal MRSA infections.     

主动监测培养对于控制院内MRSA感染的效果

目的探讨主动监测培养对于住院患者耐甲氧西林金黄色葡萄球菌（MRSA）感染控制情况的效果。方法统计沈阳军区总医院2011-2013年MRSA培养阳性率、感染率等相关数据,以6个月为单位,对实施主动监测培养前后各时间段情况进行比较。结果实施监测培养后MRSA培养阳性人数一度增加,由原平均每月不足10人,增至2012年下半年的平均约12人/月。后逐渐下降,2013年下半年降至约平均9人/月,与2012年上半年相比,差异有统计学意义（P〈0.05）。MRSA感染发病率在实施监测培养后呈下降趋势,由最初1.3‰-1.4‰降至2013年下半年的0.49‰,该数值与2013年上半年相比差异有统计学意义（P〈0.05）。抗MRSA抗生素使用量在引入监测培养后减少。2013年下半年用量降至约平均65支/月,与2013年上半年相比,差异有统计学意义（P〈0.05）。结论主动检测培养为院内原有MRSA感染检测的重要补充。若MRSA筛查培养阳性可早期采取相应干预手段,有效防止院内感染发生,促进了抗生素的合理应用。     

Potent In Vitro Bactericidal Activity of Polymyxin B against Methicillin-Resistant Staphylococcus aureus (MRSA)

Eradication of methicillin-resistant Staphylococcus aureus (MRSA) carried by inpatients or healthy hospital personnel by topical use of antibiotics is an important step for preventing outbreak of MRSA nosocomial infection. In the screening of the antibiotic best suited for this purpose, we have found that polymyxin B, a commonly used antibiotic for gram-negative infection, had an unexpected strong cytokilling activity towards MRSA clinical strains, which was more potent than that of vancomycin or gentamicin. The data suggested that polymyxin B could be an antibiotic of choice in the treatment of topical carriage of or infection caused by MRSA.     

Antimicrobials, drug discovery, and genome mining

Over the years, antibiotics have provided an effective treatment for a number of microbial diseases. However recently, there has been an increase in resistant microorganisms that have adapted to our current antibiotics. One of the most dangerous pathogens is methicillin-resistant Staphylococcus aureus (MRSA). With the rise in the cases of MRSA and other resistant pathogens such as vancomycin-resistant Staphylococcus aureus, the need for new antibiotics increases every day. Many challenges face the discovery and development of new antibiotics, making it difficult for these new drugs to reach the market, especially since many of the pharmaceutical companies have stopped searching for antibiotics. With the advent of genome sequencing, new antibiotics are being found by the techniques of genome mining, offering hope for the future.     

深圳市人民医院近五年临床分离金黄色葡萄球菌的 分布及耐药性分析

目的分析医院感染患者金黄色葡萄球菌的临床分布特征及耐药性变化,为临床治疗金黄色葡萄球菌感染提供依据。方法回顾性分析2012年1月至2016年12月我院从临床各类标本中分离获得的1 141株金黄色葡萄球菌,统计其在各类标本和病区中的分布特点,并用K-B法测定该菌对常用抗菌药物的敏感性。结果 5年中共分离出1 141株金黄色葡萄球菌,标本来源构成比最多的是伤口分泌物(43.3%)、呼吸道标本(24.0%)和血液标本(10.2%)。耐甲氧西林金黄色葡萄球菌(MRSA)共有339株,占29.7%。各年MRSA的检出数依次为53株(31.9%)、51株(26.0%)、82株(35.2%)、81株(30.3%)和72株(26.0%)。MRSA主要分离自神经外科(13.8%)、呼吸监护室(10.6%)、重症监护室(8.8%)和骨科(7.7%)。MRSA对抗菌药物的耐药性普遍高于MSSA,二者比较差异有统计学意义(P0.05)。未发现对万古霉素、利奈唑胺、替考拉宁耐药的金黄色葡萄球菌。结论 MRSA感染多发生于长期使用抗菌药物,有皮肤软组织伤口及侵入性操作的科室及患者。MRSA具有多重耐药性,应严格掌握抗菌药物的使用适应证;同时临床治疗应根据药物敏感性报告针对性地合理用药,以便及时有效地控制感染并防止耐药菌株的扩散。     

Methicillin-resistant Staphylococcus aureus Bacterial Nitric-oxide Synthase Affects Antibiotic Sensitivity and Skin Abscess Development

Staphylococcus aureus infections present an enormous global health concern complicated by an alarming increase in antibiotic resistance. S. aureus is among the few bacterial species that express nitric-oxide synthase (bNOS) and thus can catalyze NO production from l-arginine. Here we generate an isogenic bNOS-deficient mutant in the epidemic community-acquired methicillin-resistant S. aureus (MRSA) USA300 clone to study its contribution to virulence and antibiotic susceptibility. Loss of bNOS increased MRSA susceptibility to reactive oxygen species and host cathelicidin antimicrobial peptides, which correlated with increased MRSA killing by human neutrophils and within neutrophil extracellular traps. bNOS also promoted resistance to the pharmaceutical antibiotics that act on the cell envelope such as vancomycin and daptomycin. Surprisingly, bNOS-deficient strains gained resistance to aminoglycosides, suggesting that the role of bNOS in antibiotic susceptibility is more complex than previously observed in Bacillus species. Finally, the MRSA bNOS mutant showed reduced virulence with decreased survival and smaller abscess generation in a mouse subcutaneous infection model. Together, these data indicate that bNOS contributes to MRSA innate immune and antibiotic resistance phenotypes. Future development of specific bNOS inhibitors could be an attractive option to simultaneously reduce MRSA pathology and enhance its susceptibility to commonly used antibiotics.     

The emergence and evolution of methicillin-resistant Staphylococcus aureus

Significant advances have been made in recent years in our understanding of how methicillin resistance is acquired by Staphylococcus aureus. Integration of a staphylococcal cassette chromosome mec (SCCmec) element into the chromosome converts drug-sensitive S. aureus into the notorious hospital pathogen methicilin-resistant S. aureus (MRSA), which is resistant to practically all beta-lactam antibiotics. SCCmec is a novel class of mobile genetic element that is composed of the mec gene complex encoding methicillin resistance and the ccr gene complex that encodes recombinases responsible for its mobility. These elements also carry various resistance genes for non-beta-lactam antibiotics. After acquiring an SCCmec element, MRSA undergoes several mutational events and evolves into the most difficult-to-treat pathogen in hospitals, against which all extant antibiotics including vancomycin are ineffective. Recent epidemiological data imply that MRSA has embarked on another evolutionary path as a community pathogen, as at least one novel SCCmec element seems to have been successful in converting S. aureus strains from the normal human flora into MRSA.     

Methicillin-resistant Staphylococcus aureus: a pervasive pathogen highlights the need for new antimicrobial development

Staphylococcus aureus (S. aureus) has entered the spotlight as a globally pervasive drug-resistant pathogen. While historically associated exclusively with hospital-acquired infections in immunocompromised hosts, the methicillin-resistant form of S. aureus has been spreading throughout communities since the 1990s. Indeed, it has now become a common household term: MRSA. S. aureus has developed numerous mechanisms of virulence and strategies to evade the human immune system, including a host of surface proteins, secreted enzymes, and toxins. In hospital intensive care units, the proportion of MRSA-related S. aureus infections has increased strikingly from just 2 percent in 1974 to 64 percent in 2004. Its presence in the community has been rising similarly, posing a significant public health burden. The growing incidence of MRSA unfortunately has been met with dwindling efforts to develop new, more effective antibiotics. The continued emergence of resistant strains of bacteria such as MRSA demands an urgent revival of the search for new antibiotics.