Induction of anti-mycobacterial and anti-listerial activity of human monocytes requires different activation signals.

The requirements for activation of anti-mycobacterial and anti-listerial activity of human monocytes were investigated. Human monocytes could be activated to display enhanced anti-mycobacterial activity by a 24-h treatment with lipopolysaccharide. The mediator induced by this treatment was identified as being tumour necrosis factor-alpha (TNF-alpha). Addition of recombinant TNF-alpha (rTNF-alpha) to the cultures of human monocytes for 24 h yielded comparable results (minimal dose required for induction of anti-mycobacterial activity, 10 U ml). Addition of anti-TNF-alpha antibody completely abrogated the effect. A similar treatment protocol failed to activate enhanced anti-listerial activity. To trigger anti-listerial activity, sequential treatment of human monocytes with rTNF-alpha and IL-2 was required. Treatment of monocytes with 10 U ml rTNF-alpha for 24 h followed by incubation in the presence of 200 U/ml of IL-2 for an additional 24 h yielded a reduction of listerial growth which was moderate but statistically significant (P less than 0.001). The activation of monocytes observed with rTNF-alpha/IL-2 treatment was (i) dependent on both cytokines; (ii) sequence dependent (i.e. when IL-2 was added prior to rTNF-alpha, no effect was observed); and (iii) absent in cells treated with one cytokine only. Enhancement of anti-listerial activity by sequential use of cytokines was not accompanied by an increase in oxidative burst, which indicated that oxidative mechanisms were not the reason for the observed Listeria monocytogenes growth restriction. Further support for this hypothesis was obtained after interferon-gamma treatment of human monocytes which led to an augmented PMA-inducible release of active oxygen radicals, but was not paralleled by growth restriction of L. monocytogenes. Our results indicate that TNF-alpha plays a crucial role in the activation of monocytes for growth restriction of intracellular microbes. Activation of human monocytes to restrict the growth of the facultative intracellular bacteria Mycobacterium avium intracellulare and L. monocytogenes, however, follows different patterns, the initial trigger in both cases being provided by TNF-alpha-induced signals.     

Recent advances in bacteriophage-based therapeutics: Insight into the post-antibiotic era

Antibiotic resistance is one of the biggest threats to global health, as it can make the treatment of bacterial infections in humans difficult owing to their high incidence rate, mortality, and treatment costs. Bacteriophage, which constitutes a type of virus that can kill bacteria, is a promising alternative strategy against antibiotic-resistant bacterial infections. Although bacteriophage therapy was first used nearly a century ago, its development came to a standstill after introducing the antibiotics. Nowadays, with the rise in antibiotic resistance, bacteriophage therapy is in the spotlight again. As bacteriophage therapy is safe and has significant anti-bacterial activity, some specific types of bacteriophages (such as bacteriophage phiX174 and Pyo bacteriophage complex liquid) entered into phase III clinical trials. Herein, we review the key points of the antibiotic resistance crisis and illustrate the factors that support the renewal of bacteriophage applications. By summarizing recent state-of-the-art studies and clinical data on bacteriophage treatment, we introduced (i) the pharmacological mechanisms and advantages of antibacterial bacteriophages, (ii) bacteriophage preparations with clinical potential and bacteriophage-derived anti-bacterial treatment strategies, and (iii) bacteriophage therapeutics aimed at multiple infection types and infection-induced cancer treatments. Finally, we highlighted the challenges and critical perspectives of bacteriophage therapy for future clinical development.     

我院2007-2009年尿培养病原菌分布及耐药性分析

目的监测与分析尿路感染患者的病原菌分布及对抗菌药物的耐药性变化,为临床合理使用抗菌药物提供依据。方法采用VITEK-32及MicroScan Walkaway40系统对送检尿培养标本中的细菌进行鉴定及药敏试验,应用上海新和软件公司的微生物软件进行数据统计分析。结果2007－2009年间我院送检的5329份尿培养标本中,阳性标本3109份,阳性率为57．7％。共分离出1253株革兰氏阴性杆菌,占40．3％;963株革兰氏阳性菌,占31．0％;893株念珠菌,占28．7％。尿路感染的病原菌以革兰氏阴性菌为主,尤以大肠埃希菌最为常见,占21．2％;而在革兰阳性菌中以肠球菌属为主,占19．7％,屎肠球菌次之,占10．7％;真菌感染的数量亦明显增加,其中光滑念珠菌居首位,占7．O％。病原菌对各种抗菌药物耐药差异性较大,表现为多药耐药;产超广谱B-内酰胺酶的大肠埃希菌、肺炎克雷伯菌和奇异变形菌的检出率分别为52．3％、58．8％和40．94％。结论尿路感染的病原菌阳性率高,其中以革兰氏阴性菌为主。病原菌对各种抗菌药物耐药差异性较大,表现为多药耐药。及时总结分析泌尿系感染的病原菌分布及耐药性,对于控制耐药菌株传播,指导临床合理选用抗菌药物具有十分重要的意义。     

对294株临床分离金黄色葡萄球菌药敏试验结果分析

目的：调查分析安徽省铜陵市人民医院临床分离的金黄色葡萄球菌分布特征与药物敏感性试验结果,为临床合理用药提供参考。方法：对本院2005-2008年临床送检标本所分离的金黄色葡萄球菌病房分布与纸片法药敏试验结果进行分析。结果：294株金黄色葡萄球菌中,骨科（28.57%）、烧伤科（11.90%）、普外科（7.48%）等科室检出率较高,标本主要有创面分泌物（49.66%）、痰（29.59%）、脓液（8.50%）等,有明显的临床分布特征。其中耐甲氧西林金黄色葡萄球菌（MRSA）检出率为27.21%（80/294）,MRSA对大环内酯类、喹诺酮类、林可霉素类等药物呈多重耐药特征,而甲氧西林敏感金黄色葡萄球菌（MSSA）相对敏感。所有金黄色葡萄球菌对青霉素、氨苄西林、氨基糖苷类药物显示高耐药率;对磺胺甲唑-甲氧苄啶（复方新诺明）、呋喃妥因、利福平、磷霉素等抗菌药物的耐药率较低（〈20%）,未发现对替考拉宁、万古霉素耐药的菌株。结论：定期进行医院细菌流行病学调查和耐药性分析对临床合理用药具有指导作用。     

抗菌药致不良反应报告分析

目的了解抗菌药不良反应发生情况,为临床合理用药提供参考。方法应用分类统计和分析评价法,对我校附属医院2009—2010年抗菌药引起的109例不良反应报告进行统计分析。结果 109例病人中,女性多于男性,46~60岁年龄段构成比最高,占46.79%;共涉及30种抗菌药,以β-内酰胺类抗菌药(包括青霉素类和头孢菌素类)引发的不良反应最多(52例,占47.71%);给药途径以静脉给药为主,占93.58%;临床表现以皮肤和消化系统损害为主,分别占32.11%和24.77%。结论抗菌药不良反应日渐增多,应充分重视不良反应的监测,合理使用抗菌药物。     

苦豆碱抗细菌感染作用机理的研究

本文通过体内外实验研究了苦豆碱抗细菌感染作用的机理。体外抑菌试验证明苦豆碱具有杀死或抑制侵袭性大肠杆菌(EIEC)生长的作用。体内试验,通过腹腔注射活的 EIEC 给小鼠,结果证明苦豆碱能提高小鼠注射 EIEC 后48h内的生存率、能增强小鼠从脾脏清除细菌的能力、能增加抗菌抗体的效价和提高红细胞免疫功能。因此,作者认为苦豆碱抗细菌感染作用的机理,除苦豆碱的直接杀菌或抑菌作用外,还可通过提高机体的免疫功能来实现。     

连续4年临床分离阴沟肠杆菌耐药监测与对策

目的 探讨阴沟肠杆菌引起医院内感染的特点以及对抗菌药物耐药性的变化趋势.方法 应用Walkaway40型全自动细菌鉴定仪对2007～2010年分离的256株阴沟肠杆菌进行鉴定和药敏试验,并进行统计学分析.结果 256株阴沟肠杆菌来源主要为伤口分泌物、痰及咽拭子、尿液、血液等,分别占51.6%、18.8%、12.5%、7.4%.对亚胺培南敏感性最高,耐药率较低(0.8%),对头孢西丁耐药率高达98.0%.近年来阴沟肠杆菌多重耐药得到有效控制,临床常用药物的耐药呈下降趋势.结论 加强阴沟肠杆菌的耐药监测、了解其耐药性变迁可合理指导临床用药,有效控制阴沟肠杆菌耐药菌株的产生.     

革兰阳性球菌治疗的优化策略

本文主要介绍葡萄球菌、链球菌和肠球菌这三种常见的革兰阳性球菌的分布及临床微生物学特性,并对这三种病原菌的耐药性进行分析,以指导目前抗生素的合理应用。此外,还介绍了部分新型抗革兰阳性球菌药物,提示耐药球菌的新型治疗药物仍处于研发阶段,更多的临床试验在逐步开展中。     

山西省243株幽门螺杆菌药物敏感性及克拉霉素耐药基因突变特征分析

目的 了解山西幽门螺杆菌（Helicobacter pylori,H.pylori）对5种抗生素药物敏感性及其克拉霉素耐药相关基因突变特征.方法 收集临床分离的H.pylori243株,采用纸片扩散法检测H.pylori对5种抗菌药物的敏感性.选取所有耐克拉霉素及相当数量的敏感菌株,提取基因组DNA,PCR法扩增23SrRNA基因功能区并测序,测序结果采用DNAStar软件包分析.统计结果分析采用x2检验和Fisher精确概率法.结果 临床分离的243株H.pylori,药敏结果显示对甲硝唑,克拉霉素,阿莫西林,左氧氟沙星和呋喃唑酮5种药物的耐药率分别为：75.3％（183/243）,7.4％（18/243）,7.4％（18/243）,12.4％（30/243）,8.6％（21/243）,5种药物的耐药率有统计学意义（P＜0.05）.结论 H.pylori临床菌株对甲硝唑,左氧氟沙星,克拉霉素、阿莫西林及呋喃唑酮存在不同程度的耐药,以对甲硝唑耐药率最高.克拉霉素耐药菌株23SrRNA基因突变以A2143C为主,此突变可能与该地区H.pylori耐药性有关,此外,还发现了A2214G位点的突变.