微生物源抗耐甲氧西林金黄色葡萄球菌天然产物的研究进展

耐甲氧西林金黄色葡萄球菌(MRSA)是目前临床上感染严重的耐药性细菌之一，给人类健康造成了巨大威胁。万古霉素为目前治疗MRSA感染的最后一道防线，但耐万古霉素金黄色葡萄球的出现使对治MRSA新型药物的开发迫在眉睫。微生物是巨大的天然化合物宝库，曾为现代抗生素工业提供了多数主力抗生素。新近研究表明，微生物源天然产物有着良好的对治MRSA的生物活性，有些已经被开发为临床治疗MRSA感染的一线药物。本文从MRSA耐药机理，新型MRSA治疗药物研究的意义，到目前常用治疗MRSA的药物，尤其针对来源于微生物拮抗MRSA的天然产物研究进行了综述，并对未来发展趋势进行了展望。     

替考拉宁、万古霉素治疗MRSA疗效及药物经济学的分析

目的分析替考拉宁、万古霉素对耐甲西林金黄色葡萄球菌(MRSA)下呼吸道感染的疗效及药学经济学。方法从我院选出治疗MRSA所致下呼吸道感染患者80例,将患者分成两组,组一41例为替考拉宁组,采用替考拉宁药物进行治疗,组二39例为万古霉素组,采用万古霉素药物进行治疗,对两组患者药物治疗疗效及药物经济学进行比较。结果万古霉素组在治疗总有效率上,明显低于替考拉宁组(P <0.05),替考拉宁组在成本-效果比值上,显著低于万古霉素组(P <0.05)。结论对MRSA引起下呼吸道感染的患者给予替考拉宁药物进行治疗,可有效的提高患者的治疗效果,减轻患者的经济负担,值得临床推广。     

抗菌药物联合应用对MRSA体外抗菌活性研究

耐甲氧西林金黄色葡萄球菌(Methicillin-resistantStaphylococcus aureus,MRSA)是医院感染和社区获得性感染的重要病原菌[1～2],对多种抗菌药物产生不同程度的耐药,所造成的感染发病率逐年上升。目前万古霉素和替考拉宁仍然是治疗MRSA的最有效药物。本研究对从临床各类感染标本中分离的30株MRSA进行了万古霉素、替考拉宁分别与左氧氟沙星联合应用的体外抑菌试验,为临床有效的治疗MRSA感染提供理论依据。1材料和方法1.1菌株来源30株MRSA来自于临床各类感染标本;标准质控菌株为金黄色葡萄球菌ATCC29213。1.2仪器与药物VITEK全自…     

中枢神经系统耐甲氧西林金黄色葡萄球菌感染治疗方案选择

万古霉素、替考拉宁、利奈唑胺是临床常用的治疗耐甲氧西林金黄色葡萄球菌(MRSA)感染的抗菌药物,由于其不同的药代动力学及不良反应特点导致其在临床应用中的侧重点各有不同。由于血脑屏障的存在,中枢神经系统感染尤其是MRSA感染的治疗尤为困难。该研究从药代动力学方面分析了替考拉宁在中枢神经系统感染中的应用以及从药物疗效、药物经济学及药物不良反应三个方面比较了万古霉素脑室给药和利奈唑胺外周静脉给药对于中枢神经系统MRSA感染的优劣,为临床颅内感染治疗方案的选择提供借鉴意义。     

万古霉素治疗药物监测和临床应用相关指南解读

目的:对美国感染病学会,美国卫生系统药师学会和感染病学药师学会的联合专家组共同制订的<万古霉素治疗成人金黄色葡萄球菌感染的治疗监测实践指南>进行解读,供临床参考.方法:阅读指南,摘要解读.结果和结论:万古霉素是目前临床治疗耐甲氧西林金黄色葡萄球菌(MRSA)的最主要的抗菌药物,<万古霉素治疗成人金黄色葡萄球菌感染的治疗监测实践指南>对万古霉素的初始剂量,血药浓度监测、血药浓度与肾毒性和耳毒性关系以及万古霉素治疗成人和儿童MRSA感染分别提出了相关建议.     

八种抗菌药对金葡菌体外抗菌活性研究及临床疗效观察

所收集的64株金葡菌中耐甲氧西林菌株(MRSA)已达50％,去甲基万古霉素和环丙沙星对MRSA和MSSA有较好抗菌活性;头孢唑林对MSSA呈高活性,而对MRSA敏感性明显低于MSSA;培氟沙星和诺氟沙星体外抗金葡菌活性较环丙沙星差;青霉素,红霉素对MRSA几乎无效。 观察了35例用培氟沙星和诺氟沙星治疗的金葡菌所致皮肤软组织感染(11例)和泌尿系感染(24例)的临床疗效。前者痊愈9/11例,有效100％,泌尿系感染MRSA12例痊愈1例、有效8例,MSSA组12例痊愈7例,有效100％。     

耐甲氧西林金黄色葡萄球菌耐药表型分型与耐药基因检测分析研究

目的分析研究耐甲氧西林金黄色葡萄球菌(methicillin-resistant staphylococcus aureus,MRSA)的耐药表型及耐药基因,探索治疗MRSA感染的有效手段。方法对临床分离的耐甲氧西林金黄色葡萄球菌株,依据美国临床实验室标准化研究所(CLSI)标准操作规程进行万古霉素、利奈唑胺和苯唑西林等药物的药物敏感性试验和耐药基因检测,分别采用微量肉汤稀释法和多重聚合酶链反应(PCR)扩增法。结果 MRSA耐药表型分为Ⅰ~Ⅶ型,MRSA对抗生素产生多重耐药,万古霉素、利奈唑胺、氯霉素、复方新诺明、利福平耐药率分别为0、7.0%、40.8%、47.9%、60.6%,β-内酰胺类药物耐药率高达100%;实验菌株mecA、ermA、ermC、tetK、tetM、ratA基因检出率分别为98.6%、60.6%、18.3%、100%、7.0%和0。结论 MRSA对万古霉素、利奈唑胺敏感,其他药物呈多重耐药,需加强MRSA对万古霉素、利奈唑胺、氯霉素、复方磺胺、利福平等常用药物最小抑菌浓度(MIC)监测和临床报告,关注万古霉素对MRSA治疗不佳患者。     

耐甲氧西林金黄色葡萄球菌肺炎小鼠感染模型的建立与评估

目的 本研究采用临床分离鉴定的ST239型耐甲氧西林金黄葡萄球菌(MRSA)感染BALB/c小鼠,建立小鼠肺炎模型,对小鼠的临床症状、肺载菌量与组织病理学变化进行时相性监测,并用该模型验证万古霉素对小鼠的治疗效果.方法 取35只小鼠随机分成MRSA感染组、药物组和对照组,通过滴鼻方式分别滴入50μL细菌(前两组)与PBS(对照组);感染一天后对药物组用同样的方式滴入万古霉素,CT检测肺部的变化,并对肺载菌量和组织病理学变化进行观察.结果 与对照组比较,CT和细菌计数等结果表明MRSA感染组和药物组的肺组织有明显的炎症反应,载菌量较高;与感染组相比,药物组小鼠肺部的载菌量明显降低,气管和肺部的组织病理学症状明显减轻.结论 本实验结果表明小鼠MRSA肺炎模型成功建立,并可用于药物疗效的比较评估.该模型的建立,将为进一步研究临床分离的MRSA的病原特性、发病机理、治疗方法等,提供可靠的小动物模型.     

2008～2011年耐甲氧西林金黄色葡萄球菌耐药性分析

目的了解笔者所在医院近年来临床分离的MRSA的耐药情况及动态变化,为临床合理选用抗菌药物提供参考和依据。方法回顾性分析医院2008～2011年临床分离的373株MRSA的耐药情况。结果 2008～2011年每年MRSA的检出率分别为43.2%(35/81)、62.8%(81/129)、56.9%(123/216)、58.5%(134/229),差异有统计学意义(P<0.05)。2008～2011年MRSA对18种抗菌药物的耐药率:青霉素、氨苄西林、阿莫西林/棒酸、头孢唑啉、亚胺培南均为100.0%;红霉素、克林霉素为92.5%～97.1%;左氧氟沙星、环丙沙星为83.6%～94.3%;庆大霉素为79.1%～88.9%;利福平为45.7%～49.3%;四环素为35.0%～47.0%;复方新诺明为32.1%～42.9%;氯霉素为11.1%～14.3%;呋喃妥因为3.3%～6.0%;奎奴普丁/达福普丁为0;利奈唑胺为0;万古霉素为0,所有抗菌药物的耐药性在4年间差异无统计学意义(P>0.05);未发现耐万古霉素、利奈唑胺及奎奴普丁/达福普丁的MRSA。结论对于MRSA感染的治疗,β-内酰胺类抗菌药物不能用;红霉素、克林霉素、左氧氟沙星、环丙沙星、庆大霉素暂停临床应用;万古霉素为首选经验用药,其次是利奈唑胺和奎奴普丁/达福普丁。     

进口万古霉素与国产去甲万古霉素治疗耐甲氧西林金葡球菌下呼吸道感染的对比研究

目的 探讨万古霉素和去甲万古霉素对耐甲氧西林金黄色葡萄球菌(MRSA)下呼吸道感染的敏感性、临床疗效和不良反应。方法 对本院呼吸疾病重症监护病房(RICU)住院的l15例MRSA所致下呼吸道感染患者采用随机配对法分为去甲万古霉素治疗组(A组，68例)和万古霉素治疗组(B组，47例)，比较两组病人的临床疗效和不良反应发生率。并对MRSA进行药敏分析。结果 两组病人l15株MRSA均对万古霉素和去甲万古霉素敏感(敏感率100％)，A、B两组临床有效率分别为80．9％和78、7％(P＞0、05)，MRSA清除率分别为80．9％和82．9％(P＞0．05)。A组有5例和B组有3例出现肾功能损害，A、B组各有2例出现皮疹。结论 国产去甲万古霉素对MRSA敏感，临床疗效良好，与进口万古霉家一致，而且不良反应较轻，适用于治疗MRSA感染。     

耐甲氧西林金黄色葡萄球菌对临床常用抗菌药物的药敏性

用琼脂稀释法测定了临床常用９种抗菌药物对７６株耐甲氧西林金黄色葡萄球菌（ＭＲＳＡ）的最小抑菌浓度（ＭＩＣ）,并根据国际推荐的ＮＣＣＬＳ的药敏标准判断ＭＲＳＡ的药敏性。验结果ＭＲＳＡ对万古霉素、去甲万古霉素、壁霉素的敏感率均为１００％;氧氟沙星、利福平、ＴＭＰ、ＳＭＺ／ＴＭＰ、庆大霉素和红霉素的耐药率介于１４．５～９２．１％。     

Clinical and economic effect of ciprofloxacin as an alternative to injectable antimicrobial therapy

The effect of the use of oral ciprofloxacin on patient outcome and the cost of antimicrobial therapy was investigated. In 1988 ciprofloxacin was placed on the antimicrobial formulary at a Veterans Affairs medical center. Patients with urinary tract infections, soft tissue infections, osteomyelitis, or pneumonia due to organisms that were documented as being susceptible to ciprofloxacin and either resistant to other oral antimicrobials or susceptible to other oral antimicrobials in patients allergic to such agents were monitored in a prospective open study over 12 months. When a patient was enrolled, the physician was asked to select the i.v. antimicrobial regimen that would have been used if ciprofloxacin were not available. Patient outcome was determined from medical records, and the difference in the costs of the oral and i.v. regimens was calculated. Clinical cure occurred in 96/100 (96%) of patients with urinary tract infection, 19/22 (86%) with soft tissue infection, 14/16 (88%) with osteomyelitis, and 10/12 (83%) with pneumonia. The overall cure rate was 139/150 (93%). The 11 clinical failures occurred in patients infected with methicillin-resistant Staphylococcus aureus (MRSA) alone, group D enterococcus alone, MRSA and Pseudomonas sp., and Pseudomonas sp. alone. The total cost avoidance achieved by using oral ciprofloxacin instead of i.v. antimicrobials was $77,158. Oral ciprofloxacin was an effective and cost-efficient alternative to traditional i.v. antimicrobial therapy in the patients studied.     

Response of complicated methicillin-resistant Staphylococcus aureus endocarditis to the addition of trovafloxacin

The newer fluoroquinolones have many properties such as safety, bioavailability, and tissue penetration that make them attractive in the therapy of complicated infections. Unfortunately, the rapid development of resistance by Staphylococcus aureus to ciprofloxacin has dampened interest in these agents for serious staphylococcal infections. A patient with right-sided methicillin-resistant Staphylococcus aureus (MRSA) endocarditis with a complicated clinical course received trovafloxacin in addition to vancomycin and rifampin. He was initially treated with vancomycin, gentamicin, and rifampin for serious MRSA infection, but because of complications, including septic central nervous system emboli, persistent fever, and leukocytosis, gentamicin was stopped and trovafloxacin begun. After this addition the patient improved and completely recovered. In vitro and animal model data show that many newer fluoroquinolones have excellent activity against S. aureus, including MRSA, and are also less likely to induce resistance. Animal models of endocarditis support their efficacy in serious staphylococcal infections.     

Agents for the Decolonization of Methicillin-Resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) bacteria are a common cause of hospital- and community-acquired infections. Persons may have asymptomatic colonization with MRSA in the nares, axillae, perineum, or groin. Since MRSA colonization often precedes infection, and infection is associated with significant morbidity and mortality, there is great interest in preventing the transmission of MRSA and decolonizing persons who harbor these bacteria. We provide an evidence-based review of MRSA decolonization agents. Our search strategy included the databases of the Cochrane Central Register of Controlled Trials, MEDLINE (1962-May 2008), and EMBASE (1980-May 2008). To identify unpublished trials, abstract books from appropriate major scientific meetings were hand searched, manufacturers were contacted, and pharmacology references were researched for available commercial products, formulations, adverse events, and dosing. The most extensive research in MRSA decolonization has been conducted with mupirocin, which is applied to the anterior nares 2–3 times/day for 5 days. Increased use is correlated to resistance development; therefore, routine decolonization is not prudent unless MRSA colonization is confirmed in the nares or other site. Retapamulin is under investigation for use in nares decolonization. If total body decolonization is necessary, bathing or showering with an antiseptic agent such as chlorhexidine gluconate is recommended in combination with mupirocin applied to the nares to improve the likelihood of eradication. Oral antibiotics have been evaluated for use in decolonization of the skin and nares but should be considered only in conjunction with topical agents and when all other decolonization attempts and environmental controls have been exhausted. Homeopathic and investigational agents may also be effective. Although mupirocin is the standard of care for decolonization of MRSA, several agents demonstrate efficacy and many merit further investigation.     

Comparison of the effect of ciprofloxacin and Tazocin on the incidence of meticillin-resistant Staphylococcus aureus (MRSA) in an Intensive Care Unit

Meticillin-resistant Staphylococcus aureus (MRSA) is a very significant agent of recalcitrant healthcare-associated infections. A major risk of acquiring such infections is thought to be modulated by the use of particular antimicrobial therapies. The aim of this research was to evaluate prospectively the impact of using either ciprofloxacin or Tazocin (piperacillin+tazobactam) on the incidence of MRSA in an Intensive Care Unit (ICU). The 1-year (2 x 6 months) cross-over study was carried out in a medium-sized (426 beds) teaching hospital. During the first 6-month period, ciprofloxacin was used as the first-line broad-spectrum antibiotic therapy of choice. During the second 6-month period, Tazocin was used as first-line therapy. The incidence of hospital-acquired MRSA (i.e. colonised and/or infected) and rates of compliance of the ICU healthcare workers to optimal hand hygiene practices were recorded throughout the study. The study observed no statistically significant differences (P = 0.1) between MRSA incidence rates in the ICU during the ciprofloxacin (4.4/1000 bed-days) or Tazocin (11.4/1000 bed-days) arms of the study. Interestingly, observing healthcare workers' hand hygiene practices throughout the entire study showed that healthcare workers adhered to these practices 59.2% of the time during the ciprofloxacin arm and 66.0% during the Tazocin arm. The low incidence rates within the unit demonstrated the importance of infection control in limiting the spread of MRSA despite the extensive use of antibiotics in a high-risk setting.     

儿科金黄色葡萄球菌感染的耐药性分析

目的对笔者所在医院儿科分离的金黄色葡萄球菌进行耐药性分析,为临床合理使用抗菌药物提供依据。方法回顾性分析笔者所在医院儿科分离的233株SAU标本来源及临床科室分布情况,并进行耐药性分析;采用VITEK-2COMPART仪器进行药敏试验,苯唑西林筛选出耐甲氧西林金黄色葡萄球菌。结果 233株SAU在痰标本及儿科重症监护室检出比例最大,分别为68.67%和31.33%;共检出MRSA40株,其检出率17.17%;在SAU中利奈唑烷、利福平、莫西沙星、喹奴普汀/达福普汀和万古霉素耐药率均为0;MRSA对红霉素、氯洁霉素、四环素、环丙沙星的耐药率显著高于甲氧西林敏感金黄色葡萄球菌,差异有统计学意义(P<0.05)。结论临床在确诊SAU感染时,应区别对待MSSA和MRSA,及时、合理使用抗生素预防和控制感染。     

泌尿系统金黄色葡萄球菌感染125例分析

目的：探讨泌尿系统金黄色葡萄球菌感染的现状，耐药性及其治疗，方法：对125株感染泌尿系的金黄色葡萄球菌进行回顾性分析。结果：本组中耐甲氧西林金黄色葡萄球菌（MBSA）89株（71.2%)。甲氧西林敏感金黄色葡萄球菌（MSSA）36株（28.8%)。医院内感染77株（61.6%)。71株为MRSA（92.2%)。MRSA对青霉素类耐药率很高，对头孢类，氨基糖甙类和新型喹诺酮类抗生素均有程度不同的耐药，而对万古霉素100%敏感。结论：金黄色葡萄球菌是泌尿系感染重要的致病菌，其中MRSA占很大比重，MRSA的治疗应在药敏试验指导下用药，对于全身重度感染，万古霉素为首选。     

Ciprofloxacin 0.3%/dexamethasone 0.1% topical drops for the management of otic infections

The American Academy of Otolaryngology – Head and Neck Surgery has recommended that, where possible, infections of the external auditory canal and middle ear be treated with topical preparations. The advantages of topical therapy include i) excellent efficacy; ii) decreased risk of systemic side effects; iii) less likelihood of selecting for resistant strains of microorganisms; and iv) lack of potential for ototoxicity. One advantage of topical therapy arises as a consequence of a very high concentration of antibiotic in topical preparations reaching the site of infection. Ciprofloxacin 0.3%/dexamethasone 0.1% (Ciprodex^®) is the only ototopical drop approved for use in both the middle ear and external auditory canal that combines a fluoroquinolone with a steroid. At 0.3% (3000 mcg/ml), the ciprofloxacin concentration of Ciprodex exceeds the MIC of virtually all relevant organisms by a very considerable margin. The clinical efficacy of ciprofloxacin/dexamethasone suspension has been demonstrated in several large prospective clinical trials. It has been consistently equal to or superior to comparator drugs. The authors believe that the use of topical ciprofloxacin/dexamethasone will increase as the advantages of fluoroquinolone/steroid combination therapy become more widely recognized.     

抗耐甲氧西林金黄色葡萄球菌感染治疗的研究进展

耐甲氧西林金黄包葡萄球菌(MRSA)是医院感染常见的致病菌,近年来医院的检出率逐渐升高,耐药程度日趋加重,已成为当今感染医学的一个亟待解决的难题。随着抗菌药物的不断开发利用,新思路及新技术在感染医学当中的应用,将开辟治疗MRSA感染的新途径。本文从不同角度介绍MRSA抗菌药物的研发、免疫治疗及RNA干扰技术在抗MRSA感染治疗中的进展。     

颅脑创伤121例耐甲氧西林金黄色葡萄球菌的耐药性分析

目的 了解颅脑创伤患者耐甲氧西林金黄色葡萄球菌(MRSA)的耐药情况,并提出对策.方法 采用纸片扩散法检测痰培养为MRSA的121例颅脑创伤病例,并对其耐药性进行统计分析.结果 121例MRSA对青霉素G、红霉素、环丙沙星、阿米卡星及头孢类抗生素耐药率达到了92.3%～100%,对替考拉宁及万古霉素完全敏感,对利福平、奈替米星、磷霉素的耐药率均较低,但对于磺胺异恶唑的耐药率从2001年的10%骤升到了2005年的95.2%.结论 MRSA的耐药性应引起高度重视,预防及合理使用抗生素是减少医院感染的重要手段.