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.     

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。     

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。     

3种中药与头孢三嗪联用对细菌释放内毒素的影响

目的:研究3种清热解毒中药与头孢三嗪联用诱导细菌释放内毒素能力的大小,为临床中、西抗菌药物联用治疗严重感染提供参考。方法:将头孢三嗪单独或与3种抗菌中药联合,体外作用于敏感的肺炎克雷伯氏菌,比较高、中、低3种浓度作用4h后细菌释放内毒素的量。结果:头孢三嗪不管是单用还是与中药联用均是低浓度组产生的内毒素量最大,高浓度组量最小;低浓度组产生内毒素的量比不加抗菌药物的对照组的量更大;双黄连与头孢三嗪联用比单用头孢三嗪产生内毒素的量更小。结论:低浓度的头孢三嗪能诱导细菌释放内毒素;双黄连能减少头孢三嗪诱导细菌释放内毒素。     

庆大霉素与3种中药联用对细菌释放内毒素的影响研究

目的:探讨3种清热解毒中药与庆大霉素联用诱导细菌释放内毒素能力的大小,为临床中、西抗菌药物联用治疗严重感染提供参考。方法:比较高、中、低3种浓度庆大霉素单独或与3种中药联合体外作用于敏感的肺炎克雷伯菌4h后细菌释放内毒素的量。结果:庆大霉素不管是单用还是与中药联用,均是低浓度组产生的内毒素量最大,高浓度组量最小;低浓度组产生内毒素的量比不加抗菌药的对照组的量更大;双黄连与庆大霉素联用比单用庆大霉素产生内毒素的量更小。结论:低浓度的庆大霉素能诱导细菌释放内毒素,双黄连与庆大霉素联用能减少细菌释放内毒素的量。     

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.     

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。     

5种抗生素对细菌释放内毒素的影响

目的研究5种临床常用的抗生素对细菌释放内毒素的影响,为临床使用抗生素提供理论依据。方法选择5种抗生素以1倍、10倍及100倍MIC浓度作用于敏感的肺炎克雷伯菌．测定作用5h之后释放内毒素的量．并做阴性对照。结果5种抗生素中,头孢曲松和哌拉西林舒巴坦钠诱导细菌释放内毒素量最大,洛美沙星和头孢呋辛次之,依替米星较低;细菌释放内毒素量1倍MIC〉10倍MIC〉100倍MIC。结论不同的抗生素诱导细菌释放内毒素的量不同。临床选用抗生素时应参考细菌释放内毒素的特性,合理选用抗生素。     

几种抗菌药对细菌释放内毒素的影响

目的：研究4种临床常用的抗菌药对细菌释放内毒素的影响,为临床使用抗菌药提供理论依据。方法：选择4种抗菌药以1倍、10倍及100倍MIC浓度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：4种抗菌药中,阿洛西林钠、阿莫西林钠／克拉维酸钾诱导细菌释放内毒素量最大,头孢哌酮次之,异帕米星较低;细菌释放内毒素量1倍MIC〉10倍MIC和100倍MIC。结论：不同的抗菌药诱导细菌释放内毒素的量不同,临床选用抗菌药时应参考细菌释放内毒素的特性,合理选用抗菌药。     

不同中西抗菌药物对肺炎克雷伯菌释放内毒素抑制作用的影响

目的:研究不同中西抗菌药物对肺炎克雷伯菌内毒素释放抑制作用的影响。方法:选取医院常用的中药(珍珠草、金银花、小柴胡等)与西药(美罗培南、左氧氟沙星注射液、氨曲南等),比较单用西药与中西药联用对肺炎克雷伯菌释放内毒素的影响。结果:与单用西药相比,中西药联用能有效降低肺炎克雷伯菌内毒素的释放。结论:对于肺炎患者,合理选用中西药联用应控制其使用剂量及其浓度,是有效降低克雷伯菌内毒素释放的方法。     

头孢他啶诱导内毒素释放及清开灵注射液抗内毒素作用的体外试验研究

目的:探讨头孢他啶对大肠埃希菌内毒素释放的影响因素及清开灵注射液体外抗内毒素活性。方法:采用二倍稀释法测定头孢他啶对大肠埃希菌的最小抑菌浓度(MIC),确定不同浓度的清开灵注射液对MIC的影响;观察2、10、50、250×MIC头孢他啶对处于对数生长期不同浓度大肠埃希菌产生内毒素的影响及125倍、250倍、500倍稀释的清开灵注射液与头孢他啶联合应用后的抗内毒素作用。结果:头孢他啶对大肠埃希菌的MIC为0.125μg·mL-1,清开灵注射液各稀释浓度对此值无影响。在较高菌浓度时,头孢他啶在杀菌的同时可诱导产生大量内毒素;在较低菌浓度时,各浓度头孢他啶抑制内毒素释放。清开灵注射液可显著对抗内毒素的产生,但无剂量依赖性。结论:头孢他啶对大肠埃希菌内毒素产生的影响与二者的浓度有关,清开灵注射液具有一定的抗内毒素作用。     

Effects of isepamicin and beta-lactam antibiotics on the release of endotoxin from Pseudomonas aeruginosa

Antibiotic-induced release of endotoxin (lipopolysaccharide, LPS) from Pseudomonas aeruginosa was investigated in in vitro with different antibiotic concentrations and in the pharmacokinetic autosimulation system. We compared the effect of isepamicin (ISP) with those of 3 beta-lactam antibiotics, piperacillin (PIPC), ceftazidime (CAZ) and imipenem (IPM). ISP showed a strong bactericidal activity, but the amount of free LPS did not increase by 6 hrs (28 +/- 2 ng/ml at 1MIC). PIPC and CAZ caused a gradual killing and a large amount of LPS release at 4 hrs (515 ng/ml and 493 ng/ml, respectively, at 1 MIC). At 1/4 x MIC, PIPC and CAZ did not reduce colony forming counts and induced more release of free LPS. The organism treated with IPM released less LPS, while it was killed rapidly. The viable cell counts decreased dramatically after administration of ISP in the pharmacokinetic autosimulation system. ISP inhibited the bacterial regrowth and the following release of free LPS by 8 hrs. Great amounts of free LPS were released 4 hrs after the administration of PIPC and CAZ in the simulation system, associated with morphological changes; elongation, cell lysis or regrowth. IPM showed a strong bactericidal activity and less liberation of free LPS, but the free LPS level increased at 8 hrs, accompanied by the regrowth of the organism. The total amounts of LPS released by P. aeruginosa PAO1 in 8 hours of the pharmacokinetic simulation system were as follows; ISP < IPM < CAZ < PIPC.     

3种中药对细菌释放内毒素的影响

目的研究肿节风、新鱼腥草素钠及穿琥宁注射液对肺炎克雷伯菌释放内毒素能力的影响。方法以头孢三嗪为阳性对照品,将3种中药单独或与头孢三嗪联用,体外作用于敏感的肺炎克雷伯菌,比较高、中、低3种浓度作用4h后细菌内毒素释放量。结果无论是单用还是与头孢三嗪联用,3种中药都与头孢三嗪一样,均是低浓度组产生的内毒素量最大,高浓度组量最小,低浓度组产生的内毒素量比不加任何抗茵药物的阴性对照组更大。结论3种中药抗菌药物对肺炎克雷伯菌释放内毒素的影响类似头孢三嗪。     

鸡蛋清溶菌酶对头孢他啶诱导铜绿假单孢菌内毒素释放的抑制作用

目的研究鸡蛋清溶菌酶（lysozyme, LZM）对头孢他啶（ceftazidime, CFT）诱导的铜绿假单孢菌内毒素释放的影响。方法在肉汤或稀释血液培养的铜绿假单孢菌液中加入LZM、CFT或LZM/CFT，作用一定时间后，测定培养上清液中的内毒素浓度；将细菌培养上清液加入到巨噬细胞RAW 264.7中或注射入小鼠体内，测定其炎性因子(NO和TNF-α)诱生能力。结果在肉汤培养和血液培养中，CFT引起铜绿假单孢菌迅速溶解和释放大量内毒素到培养上清液中，其上清液在体外培养的巨噬细胞上和小鼠体内可诱导大量NO和TNF-α产生。而LZM与CFT联合使用能阻止细菌溶解，降低细菌内毒素释放，减少炎性因子NO和TNF-α的产生。结论LZM与CFT联合使用能抑制内毒素大量释放，减轻内毒素血症。     

Bacterial cell wall compounds as promising targets of antimicrobial agents II. Immunological and clinical aspects

The bacterial cell wall represents the primary target for antimicrobial agents. Microbial destruction is accompanied by the release of potent immunostimulatory membrane constituents. Both Gram-positive and Gram-negative bacteria release a variety of lipoproteins and peptidoglycan fragments. Gram-positive bacteria additionally provide lipoteichoic acids, whereas Gram-negative bacteria also release lipopolysaccharide (LPS, endotoxin), essential component of the outer leaflet of the bacterial cell wall and one of the most potent immunostimulatory molecules known. Immune activation therefore can be considered as an adverse effect of antimicrobial destruction and killing during anti-infective treatment. In contrast to antibiotics, the use of cationic amphiphilic antimicrobial peptides allows both effective bacterial killing and inhibition of the immunostimulatory effect of the released bacterial membrane constituents. The administration of antimicrobial peptides alone or in combination with antibiotic agents thus represents a novel strategy in the antiinfective treatment with potentially important beneficial aspects. Here, data are presented which describe immunological and clinical aspects of the use of antimicrobial peptides (AMPs) as therapeutic agents to treat bacterial infection and neutralize the immunostimulatory activity of released cell wall constituents.     

Estimation of antibacterial activity of various antibiotics against Pseudomonas aeruginosa by score method]

Antibacterial activity of various antibiotics against Pseudomonas aeruginosa isolated from each hospitals depends on the variety or amount of antibiotics used in each hospital. The antibiotic, which is effective to P. aeruginosa in a certain hospital is not always effective to that in other hospital. The excellent antibiotics in antibacterial activity have low MIC and hard to progress in resistance, and such antibiotics may be effective against P. aeruginosa isolated from any hospitals. Therefore we thought that the antibiotic, which was progress to resistance, would show a great difference in MIC among hospitals, and we investigated MIC and difference of MIC of various antibiotics against P. aeruginosa isolated from six hospitals. Furthermore, we converted the data of MICs and difference of MIC among six hospitals into the score, and tried to estimate antibacterial activity of various antibiotics by using those scores. From the results of analysis in this report, we think the antibiotics actually surpass in antibacterial activity may be imipenem, cefozopran, cefsulodin and amikacin. New analytical method proposed in this report will become one of potential methods to estimate antibacterial activity of antibiotics against bacteria isolated from inpatient with bacterial infections.