抗菌药物诱导内毒素释放及抗内毒素药物研究进展

不同种类抗菌药物诱导内毒素释放情形不同。主要作用于青霉素结合蛋白(PBP)的抗菌药物有β 内酰胺类，可杀灭菌体而释放大量内毒素(LPS)，而非作用于PBP的抗菌药物有氨基苷类、喹诺酮类、大环内酯类，使细菌释放内毒素较少。在保证有效杀菌的前提下，选择致内毒素释放较少的抗菌药物，并合用抗内毒素药物对减轻机体损伤及预防多脏器功能衰竭的发生可能有益。     

内毒素致病机理与抗内毒素药物研究概况

本文报告了国内外抗内毒素药物的研究进展。内毒素致病机理研究；药物抗内毒素作用机理及抗内毒素药物设计。分析了多粘菌素B九肽、类脂A结构拮抗剂、抗脂多糖抗体及免疫治疗、抗内毒素多肽以及中药对内毒素的作用。对新药筛选研制和临床内毒素引发疾病治疗有一定意义。     

抗菌药物联合中药对细菌释放内毒素的影响研究

目的探讨抗菌药物与清热解毒中药联用对细菌释放内毒素的影响,为临床中、西抗菌药联用治疗严重感染提供理论依据。方法将穿琥宁、喜炎平分别与头孢噻肟、左氧氟沙星、阿米卡星抗菌药物混合,以1倍、10倍及100倍最小抑菌浓度(MIC)作用于敏感的肺炎克雷伯菌,测定作用4h之后释放内毒素的量,并做阴性对照。结果 3种抗菌药物中,头孢噻肟钠诱导细菌释放内毒素量最大,左氧氟沙星次之,阿米卡星较低;2种中药注射液与抗菌药物联用比单用抗菌药物诱导细菌释放的内毒素量少,单用与联用抗菌药细菌释放内毒素量均为1倍MIC>10倍MIC>100倍MIC。结论穿琥宁和喜炎平注射液与头孢噻肟钠、左氧氟沙星、阿米卡星3种抗菌药物联用,能减少细菌诱导释放内毒素,提示临床选用中药与抗菌药物联用时应参考细菌释放内毒素的特性。     

不同抗菌药物对肺炎克雷伯菌释放内毒素的影响

目的:探讨单用或联合使用不同浓度的抗菌药物诱导细菌释放内毒素能力的大小,为临床合理选用抗菌药物提供参考.方法:选择9种常用的抗菌药物以1倍、10倍及100倍MIC浓度单独或联合作用于敏感的肺炎克雷伯菌,测定作用4 h之后释放内毒素的量.结果:单用或联用氨基糖苷类药物方案诱导细菌释放内毒素量较小,单用或联用氟喹诺酮类药物方案中等,而单用β-内酰胺类药物方案诱导细菌释放内毒素量较多;低浓度的抗菌药物比高浓度时诱导细菌释放内毒素量更多.结论:应参考诱导细菌释放内毒素的特性,合理选用抗菌药物.     

几种抗菌药物诱导肺炎克雷伯菌释放内毒素的体外实验

目的:探讨不同抗菌药物诱导细菌内毒素释放潜能的大小,为临床合理选择抗菌药物提供参考.方法:选择4种抗菌药物单独作用于敏感的肺炎克雷伯菌,比较4 h后释放细菌内毒素的量.结果:阿米卡星释放内毒素最少,头孢他啶次之,头孢吡肟及氟氧头孢钠释放内毒素最多.结论:不同抗菌药物诱导细菌内毒素释放量不同.     

抗菌药物联合中药对细菌释放内毒素的影响研究

目的 探讨抗菌药物与清热解毒中药联用对细菌释放内毒素的影响,为临床中、西抗菌药联用治疗严重感染提供理论依据.方法 将穿琥宁、喜炎平分别与头孢噻肟、左氧氟沙星、阿米卡星抗菌药物混合,以1倍、10倍及100倍最小抑菌浓度(MIC)作用于敏感的肺炎克雷伯菌,测定作用4h之后释放内毒素的量,并做阴性对照.结果 3种抗菌药物中,头孢噻肟钠诱导细菌释放内毒素量最大,左氧氟沙星次之,阿米卡星较低;2种中药注射液与抗菌药物联用比单用抗菌药物诱导细菌释放的内毒素量少,单用与联用抗菌药细菌释放内毒素量均为1倍MIC＞10倍MIC＞100倍MIC.结论 穿琥宁和喜炎平注射液与头孢噻肟钠、左氧氟沙星、阿米卡星3种抗菌药物联用,能减少细菌诱导释放内毒素,提示临床选用中药与抗菌药物联用时应参考细菌释放内毒素的特性.     

清热解毒中药联用抗菌药物对细菌释放内毒素的影响

目的：探讨清热解毒中药与抗菌药物联用对细菌释放内毒素的影响。方法：将双黄连、板蓝根、清开灵和鱼腥草4种中药分别与头孢曲松、环丙沙星、庆大霉素3种抗菌药混合，加入肺炎克雷伯菌，37℃培养4h后，测定各样品的杀菌率和释放内毒素的量。结果：头孢曲松、环丙沙星和庆大霉素3种抗菌药物不管是单用还是联用清热解毒中药其杀菌率均在92％以上，联用与不联用中药各组间差异无显著性。但是细菌产生内毒素的量却有显著不同，3种抗菌药物均是联用双黄连或板蓝根各组产生内毒素的量显著低于单用抗菌药物组。而联用与不联用清开灵和鱼腥草各组间差异无显著性。结论：双黄连和板蓝根与头孢曲松、环丙沙星和庆大霉素3种抗菌药物合用，能减少诱导细菌产生内毒素。     

内毒素血症病机及中西医结合治疗研究进展

内毒素血症是现代医学面临的一个常见而复杂的难题。内毒素是革兰阴性菌的主要成分,抗菌药物在杀菌的同时会诱导内毒素的产生,增加治疗难度。中药制剂显示出了很好的抗内毒素作用,中西医结合比单纯西医治疗效果要好,常见的疗法有清热解毒、活血化瘀、通腑下泻、益气养阴。     

抗菌药物对细菌释放内毒素的影响

为治疗革兰氏阴性菌(Gram-Negative Bacterial，GNB)引起的细菌感染，人们使用了各类高效广谱的抗菌药物，但其细菌感染致脓毒血症死亡率仍居高不下。近年来国内外的研究表明，由抗菌药物诱导细菌内毒素(Endotoxin，又名脂多糖Lipopolysaccharide，LPS)的释放可能是GNB感染治疗失败的原因之一。     

4种抗菌药物诱导肺炎克雷伯菌释放内毒素特性的研究

目的 :探讨4种抗菌药物不同浓度、不同作用时间诱导细菌释放内毒素能力的大小 ,为临床合理用药提供参考。方法 :选择4种敏感抗菌药物单独作用于肺炎克雷伯菌 ,测定1倍、10倍、100倍最低抑菌浓度 (MIC)作用于细菌1、2、4、8h释放内毒素的量。结果 :头孢曲松钠和美罗培南诱导细菌释放内毒素量最大 ,环丙沙星中等 ,庆大霉素较低 ;细菌释放内毒素量1倍MIC>10倍MIC>100倍MIC ;抗菌药物作用时间越长 ,内毒素释放的量越大。结论 :临床医师选用抗菌药物应参考其诱导细菌释放内毒素的特性。     

四季青水煎液体外抗内毒素、抗菌和体内抗炎作用

目的 研究四季青水煎液的抗内毒素、抗菌和抗炎作用,揭示四季青清热解毒作用的药效学特点。方法 采用体外鲎试剂凝集实验方法检测其抗内毒素作用;采用琼脂二倍稀释法测定四季青水煎液以及与头孢噻肟、左氧氟沙星和庆大霉素联合使用时对25株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)、产超广谱β-内酰胺酶(extended-spectrum β-lactamase, ESBLs)大肠埃希菌、非产ESBLs大肠埃希菌和铜绿假单胞菌的最低抑菌浓度(minimum inhibitory concentration, MIC);采用二甲苯致小鼠耳廓炎症肿胀法观察其抗炎作用。结果 四季青水煎液在生药浓度6.25~100mg/mL时具有抗内毒素作用;对受试菌株MSSA、MRSA的MIC范围均为8~33mg/mL,对产ESBLs大肠埃希菌及非产ESBLs大肠埃希菌的MIC范围均为33~>133mg/mL,对铜绿假单胞菌的MIC为33~133mg/mL;与头孢噻肟、左氧氟沙星和庆大霉素联合使用时抗菌活性有相加作用,分级抑菌浓度(fractional inhibitory concentration, FIC)指数范围为0.5相似文献   

Marine lipids as building blocks for soft quaternary ammonium compounds and their antibacterial activity

Environmental friendly antibacterial agents have to degrade relatively rapid to non-toxic and inactive products after they have had their desired effect. Environmental friendly quaternary ammonium agents were designed according to Bodor's soft drug approach and evaluated in vitro. Structure-activity relationship (SAR) studies showed that the antibacterial activity of a given soft agent will only be acceptable if its chemical stability is adequate to allow the agent to express its activity for sufficient duration of time. However, the studies also showed that increasing the lipophilicity of a chemically labile antibacterial agent could increase its potency. Two of the lipophilic quaternary ammonium antibacterial agents evaluated had minimum inhibitory concentration (MIC) against Staphylococcus aureus as low as 2 microg/ml and estimated degradation half-life less than 4 to 6 days at room temperature. Decreased MIC could only be obtained by increasing the degradation half-life of the agents.     

Section Review: Endotoxaemia and novel therapies for the treatment of sepsis:Pulmonary-Allergy,Dermatological, Gastrointestinal & Arthritis

Numerous agents have been developed with specific binding and inhibitory activity against endotoxin which have all shown promise in preclinical evaluations through the protection of animals against endotoxin challenge. The results of the clinical trials of agents published to date have not met the expectations generated by the results of the pre-clinical studies. A concept not reflected in animal models is that Gram-negative sepsis is a heterogeneous entity: not all patients are either bacteraemic or endotoxaemic. Sub-groups of patients that could be recognised prospectively using newer methods may not respond equally to anti-endotoxin agents. The future success of these therapeutic modalities will probably depend on our ability to identify and target the therapies to those patients who will benefit most, possibly through the application of an assay for endotoxaemia.     

Effects of polymyxin B on selected features of equine carbohydrate overload

Gram negative endotoxins play a contributory role in the syndrome which results from over consumption of carbohydrates by horses and ponies. Since the antibiotic polymyxin B exerts a direct anti-endotoxin effect by chemically modifying the active lipid A moiety of endotoxin, it might be expected to protect horses after carbohydrate overload and provide a new therapeutic and experimental tool for this condition. The present study was undertaken to evaluate the effect of polymyxin B on hemostatic, hemodynamic, acid-base, and clinical aspects of the syndrome resulting from carbohydrate overload. Experimentally-induced carbohydrate overload resulted in lactic acidosis, hypercoagulability, hypovolemic shock and lameness. Although there was a slight delay in the onset of clinical signs resulting from experimental carbohydrate overload in treated animals, polymyxin B administered iv at 2.5 mg/kg every 6 hr failed to significantly ameliorate the coagulopathy, acidosis, lameness and shock induced by alimentary carbohydrate overload.     

板蓝根中主要化学成分含量测定方法研究进展

板蓝根为十字花科植物菘蓝的干燥根,为清热解毒、凉血利咽的代表性中药,具有抗菌、抗病毒、抗内毒素、抗肿瘤及免疫调节作用。目前,采用色谱等技术已从板蓝根中分离出近200种化合物,主要包括核苷类、木脂素类、氨基酸类、生物碱类、有机酸类、多糖类及其他。该文对板蓝根主要化学成分的分离和含量测定的研究进展进行了系统综述,为进一步开展板蓝根相关研究提供参考。     

替硝唑注射液的细菌内毒素检测

目的: 建立替硝唑注射液细菌内毒素检测方法.方法: 应用不同厂家鲎试剂对替硝唑注射液进行干扰实验.结果: 替硝唑注射液2倍稀释液对细菌内毒素不产生干扰.结论: 细菌内毒素检测方法可取代替硝唑注射液热原的检查.     

Towards Clinical Applications of Anti-endotoxin Antibodies; A Re-appraisal of the Disconnect

Endotoxin is a potent mediator of a broad range of patho-physiological effects in humans. It is present in all Gram negative (GN) bacteria. It would be expected that anti-endotoxin therapies, whether antibody based or not, would have an important adjuvant therapeutic role along with antibiotics and other supportive therapies for GN infections. Indeed there is an extensive literature relating to both pre-clinical and clinical studies of anti-endotoxin antibodies. However, the extent of disconnect between the generally successful pre-clinical studies versus the failures of the numerous large clinical trials of antibody based and other anti-endotoxin therapies is under-appreciated and unexplained. Seeking a reconciliation of this disconnect is not an abstract academic question as clinical trials of interventions to reduce levels of endotoxemia levels are ongoing. The aim of this review is to examine new insights into the complex relationship between endotoxemia and sepsis in an attempt to bridge this disconnect. Several new factors to consider in this reappraisal include the frequency and types of GN bacteremia and the underlying mortality risk in the various study populations. For a range of reasons, endotoxemia can no longer be considered as a single entity. There are old clinical trials which warrant a re-appraisal in light of these recent advances in the understanding of the structure-function relationship of endotoxin. Fundamentally however, the disconnect not only remains, it has enlarged.     

干预前后我院Ⅰ类清洁手术预防性应用抗菌药物分析

目的:探讨实施干预措施对我院Ⅰ类清洁手术预防性应用抗菌药物的作用。方法:对我院2010年6-10月(干预前)及2011年6-10月(干预后)甲状腺、乳腺、疝气修补术3种Ⅰ类清洁手术围术期预防性应用抗菌药物进行回顾性分析。结果:干预后抗菌药物的应用率、用药选择、给药时长等较干预前有较大改进,但术中追加抗菌药物的情况还有待改进。结论:医院对围术期预防性应用抗菌药物实施干预,可促进临床安全、有效、经济、合理用药。     

Inhalation toxicology models of endotoxin- and bioaerosol-induced inflammation

Inhalation toxicology studies in rodents have proven their usefulness for furthering our understanding of the causal agents, mechanisms, and pathology associated with exposures to environmental endotoxins and bioaerosols. Inhalation animal models are used to determine which components of a mixture are the most important toxicants for inducing the observed adverse outcome. They are used to obtain exposure-response relationships for allergens and pro-inflammatory agents to help elucidate disease mechanisms and contribute quantitative data to the risk assessment process. Inhalation models serve as important adjuncts to epidemiology studies and human exposure studies. They are also useful for establishing phenotype in studies of genetic polymorphisms and disease susceptibility and are widely applied for evaluation of safety and efficacy for potential therapeutic agents. In order to produce reliable data, rigorous exposure chamber design, aerosol generation systems, exposure quantitation and experimental protocols must be utilized.