磷霉素钙单药及联用对大肠杆菌抑制试验

试验通过磷霉素钙单药及与其他抗生素联用对大肠杆菌的体外抑制试验,找出与其联用抑菌效果最佳的抗生素,为研制磷霉素钙的复方制剂及临床联合用药提供理论依据。1材料和仪器1.1药品(见表1)表1试验药品序号药品名批号含量生产厂商1磷霉素钙(P-Ca)20041123690U/mg东北制药总厂2酒石酸泰乐菌素(TL)A20050233912U/mg宁夏多维泰瑞制药有限公司3氧氟沙星(OF)05042295.3%浙江新昌朗博药业公司4头孢拉定(TP)2004122092.6%华北制药集团5磺胺嘧啶钠(SD)05031499.1%上海鼎星生物科技有限公司1.2试剂及菌种肉汤培养基、水解酪蛋白琼脂培养基、MH肉…     

TMP和DVD对两种磺胺药抗球虫增效作用试验

以雏鸡柔嫩艾美耳球虫病为模型,以相对存活率、相对增重率、盲肠病变值和盲肠卵囊值为观察指标,以抗球虫指数(ACI)为判定标准,观察甲氧苄啶(TMP)和二甲氧苄啶(DVD)与不同浓度磺胺喹口恶啉(SQ)和磺胺氯吡嗪钠(Esb3)联合用药治疗效果和增效作用.结果显示,药物对照组0.02%SQ和0.06% Esb3的ACI值分别为151和162;TMP与0.01%、0.02%、0.05%的SQ联用的ACI分别为177、181和195; DVD分别与0.01%、0.02%、0.05%的SQ联用的ACI分别为177、194和194;TMP与0.03%、0.06%、0.12%的Esb3联用的ACI分别为181、188和192;DVD与0.03%、0.06%、0.12%的Esb3联用的ACI分别为185、187和191.结果表明,TMP和DVD能明显提高SQ和Esb3的抗球虫效果, TMP和DVD之间的抗球虫增效作用无明显的差异.     

甲氧苄啶、二甲氧苄啶与磺胺氯吡嗪钠联用的抗球虫效果比较

选用220只10日龄海兰褐公雏口服柔嫩艾美耳孢子化卵囊制造人工感染球虫病模型,对不同浓度的磺胺氯吡嗪钠(Esb3Na)以5:1比例与甲氧苄啶(TMP)、二甲氧苄啶(DVD)联合应用的抗球虫增效作用进行比较.结果表明:高剂量Esb3Na(0.06%)与TMP或DVD联用均呈高效,抗球虫指数(ACI)分别为180.32和181.30,二者之间无明显差异.中、低剂量Esb3Na (0.03%、0.015%)与TMP联用的ACl分别为181.56和129.38,抗球虫效果强于与DVD联用,对应的ACI分别为169.68和106.19.推荐使用0.03%的Esb3Na与TMP以5:1联用防治鸡球虫病感染.     

复方磺胺间甲氧嘧啶缓释型注射液的毒性研究

复方磺胺间甲氧嘧啶缓释型注射液,由磺胺间甲氧嘧啶(SMM)与甲氧苄啶(TMP)通过环糊精包合而成,具有缓释长效、复方增效等作用.为评价该制剂的安全性,笔者进行了急性毒性、蓄积毒性和耐受性研究,旨在为临床应用提供科学依据.     

甲氧苄啶对金银花体外抗菌增效作用及量效关系的试验

金银花为常用传统中药,具有清热解毒、抗多种病原微生物、免疫增强、消除耐药质粒等多种功效[1].而甲氧苄啶(TMP)作为合成抗菌药,本身抗菌作用较弱,一般不单独应用;临床上TMP主要用作磺胺类药物的抗菌增效剂,其还可以增强多种抗生素类药物以及中草药的抗菌作用[2-3].但目前有关TMP对金银花的抗菌增效作用研究较少,尤其增效的剂量关系研究未见报道.本试验旨在通过研究金银花与TMP联用的性质和增效的剂量关系,从而确定TMP对金银花抗菌增效的最佳剂量,为中西药复方制剂的开发提供基本理论支持.     

甲氧苄啶对黄芩苷体外抗菌增效作用的试验

黄芩苷是从唇形科植物黄芩的干燥根中提取的一种黄酮类化合物,具有抗菌、消炎和免疫调节等多种药理作用[1].甲氧苄啶(TMP)为广谱抗菌增效剂,临床上常与磺胺类药物联用以增强磺胺类药物的了抗菌效果,其还可增强多种抗生素以及中药的抗菌作用[2-3].而关于TMP对黄芩苷的抗菌增效作用未见报道.为了探讨TMP对黄芩苷抗菌活性的影响,促进黄芩苷在防治畜禽传染性疾病上的应用,进行黄芩苷与TMP联用的性质和增效剂量关系的试验,并确定TMP对黄芩苷体外抗菌增效的最佳剂量,为开发高效中药复方抗菌制剂奠定基础.     

复方磺胺氯吡嗪钠不同组方与剂型对鸡球虫病的疗效

通过动物体内试验,比较复方磺胺氯吡嗪钠的不同组方与剂型对鸡球虫病的疗效。第一次试验设磺胺氯吡嗪钠+三甲氧苄啶(TMP)溶液组(0.02%,5 d)、磺胺氯吡嗪钠+TMP混悬液组(0.02%,5 d)、磺胺氯吡嗪钠+二甲氧苄啶(DVD)混悬液组(0.02%,5 d)、药物对照组(磺胺氯吡嗪钠可溶性粉,0.03%,5 d)、感染不用药组和不感染不用药组。第二次试验设磺胺氯吡嗪钠+TMP混悬液组(0.02%,5 d)、磺胺氯吡嗪钠+DVD混悬液组-1(0.02%,5 d)、磺胺氯吡嗪钠+DVD混悬液组-2(0.02%,3 d)、药物对照组(磺胺氯吡嗪钠可溶性粉,0.03%,3d)、感染不用药组和不感染不用药组。每组30只鸡。以血便记分、存活率、增重及相对增重率、病变记分与病变值、卵囊产量与卵囊值、抗球虫指数(ACI)等指标综合评定抗球虫效果。结果显示:磺胺氯吡嗪钠+TMP混悬液组(0.02%,5 d)和磺胺氯吡嗪钠+DVD混悬液组(0.02%,5 d)的抗球虫指数始终大于或接近180,为抗球虫高效水平;磺胺氯吡嗪钠+TMP溶液组(0.02%,5 d)、磺胺氯吡嗪钠+DVD混悬液组(0.02%,3 d)的抗球虫指数大于160,为抗球虫中效水平。提示:磺胺氯吡嗪钠+TMP混悬液(0.02%,5 d)和磺胺氯吡嗪钠+DVD混悬液(0.02%,5 d)对鸡球虫有较好的疗效。     

硫酸庆大霉素与甲氧苄氨嘧啶联合用药对鸡大肠杆菌、葡萄球菌的药敏试验

不少文献报道,甲氧苄氨嘧啶(TMP)对部分抗生素药物有一定的增效作用。为进一步了解它的联合用药药敏效果,特对庆大霉素与TMP进行了体外抑菌浓度指数(FIC)测定试验,结果表明,对鸡大肠杆菌FIC为0.75;对葡萄球菌FIC为1.0。抑菌效果有相加作用。     

甲氧苄啶与抗菌药物联合抗菌作用效果试验

主要以液体试管法和棋盘法测定3种抗菌药物和甲氧苄啶的最低抑菌浓度(MIC)，并以各药的小数抑菌浓度(nc)及小数抑菌浓度指数判断甲氧苄啶(TMP)与各药联合作用效应来评价TMP对不同抗菌药物的增效作用，确定其与抗菌药物最佳配伍比例。测定结果表明，TMP与受试药联合应用均产生协同作用，抗菌作用明显增强。TMP与不同抗菌药物配伍的最佳比例，因药物和受试菌株不同而异。     

三甲氧苄氨嘧啶与磺胺嘧啶:对小猎兔犬实验性感染兽疫链球菌的治疗作用

本试验报导了小猎兔犬以兽疫链球菌(Streptococcus Zooepidemicus)人工感染之后,用三甲氧苄氨嘧啶(TMP为一种增效剂)与磺胺嘧啶(SDZ)的啇用制剂tribrissen(TRI)进行治疗之后,证明这种药品优于其他的同类制剂。方法是与磺胺二甲氧基嘧啶(SDM)作效力比较试验,皮下注射两次,剂量相同。比较的项目有:(1) 临床症状观察。(2) 血液学的变化。(3) 血液培养试验。(4) 组织培养试验。根据四项测定结果:TMP与SDZ制剂的治疗效果,比其他同类制剂优良。测定TRI     

环丙沙星与甲氧苄氨嘧啶（TMP）的体外联合抑菌研究

为了检测氟喹诺酮类药物与甲氧苄氨嘧啶(TMP)联合用药产生的作用,作者进行了环丙沙星与TMP联用的体外抑菌试验。先用试管二倍稀释法测定两种药对13 种23 株病原菌的最小抑菌浓度,再用棋盘稀释法测定其FIC指数,判断联合药敏效果。结果表明,在20 株细菌对两种药联合药敏试验中,呈增强作用的占20% ,相加作用的占15% ,无关作用的占65% ,无出现拮抗作用。故除用药前确诊病原菌,并对联合药敏试验呈协同作用者,一般不应将环丙沙星与TMP联合使用。     

阿莫西林和硫酸粘菌素对猪鸡大肠杆菌和沙门氏菌的体外联合抗菌作用

探讨了阿莫西林与硫酸粘菌素对猪鸡的大肠杆菌和沙门氏菌的联合抗菌效果。采用微量稀释法分别测定阿莫西林与硫酸粘菌素单药对大肠杆菌和沙门氏菌的最低抑菌浓度（MIC）,采用棋盘稀释法测定阿莫西林与硫酸粘菌素联用对大肠杆菌和沙门氏菌的MIC并计算联合指数（FIC）。试验结果显示,对14株试验菌株体外联合抗菌呈协同与相加作用的占78.6%,呈无关作用的占21.4%,无拮抗作用,表明阿莫西林和硫酸粘菌素可联合应用于治疗猪鸡大肠杆菌和沙门氏菌感染。     

Concentrations of trimethoprim and sulfamethoxazole in cerebrospinal fluid and serum in mares with and without a dimethyl sulfoxide pretreatment.

Each of seven mares was given an intravenous (IV) injection of 40% dimethyl sulfoxide (DMSO) at a dosage of 1 g/kg, over 35 min, immediately followed by a single IV injection of a trimethoprim (TMP) and sulfamethoxazole (SMZ) combination (SMZ 83%, TMP 17%) at a combined dosage of 44 mg/kg (7.48 mg/kg TMP; 36.52 mg/kg SMZ). Each horse served as its own control and was alternately treated with an identical dose of TMP-SMZ treatment alone at least seven days following or preceding the DMSO and TMP-SMZ treatment. Serum and cerebrospinal fluid (CSF) concentrations of TMP and SMZ were measured over a six hour period. Dimethyl sulfoxide treatment caused no significant difference in the mean serum concentration of SMZ or in the mean CSF concentrations of TMP or SMZ. The mean serum concentration of TMP was significantly (p less than 0.05) increased at the two, four and six hour sampling time in the mares receiving pretreatment with DMSO. The clearance of TMP was also significantly (p less than 0.05) decreased from 675 mL/h/kg to 327 mL/h/kg by DMSO administration. Concentrations of TMP and SMZ in the CSF in both treatment groups exceeded the minimum inhibitory concentrations for many common bacterial pathogens of equine origin. In addition, CSF concentration of TMP exceeded the serum concentrations required for 50% inhibition of dihydrofolate reductases of protozoan origin. Serum TMP and SMZ concentration were similar to those reported to be effective against Toxoplasma gondii in in vitro studies on the killing or inhibition of the organism.     

恩诺沙星与硫酸丁胺卡那霉素对奶牛乳房炎常见病原菌的联合药敏试验

本试验对恩诺沙星和硫酸丁胺卡那霉素在4种奶牛乳房炎常见病原菌（无乳链球菌、化脓链球菌、金黄色葡萄球菌、致病性大肠埃希氏菌）联合药敏试验中的相互作用进行了研究。结果表明,恩诺沙星和硫酸丁胺卡那霉素对各菌的MIC为8～64μg／mL,二者联合后的FIC指数范围为0．5～1,二者联合用药时为协同作用或相加作用。     

阿散酸-TMP的制备与体外抗菌活性研究

以阿散酸和甲氧苄啶(TMP)为原料,制备阿散酸-TMP,采用IR、熔点对其进行了表征;正交试验确定了最优反应条件为:反应温度80 ℃,反应时间3 h,反应物料比1.1∶1(阿散酸∶TMP)。通过体外抑菌试验来测试其抑菌效果,结果表明,阿散酸-TMP对5种供试菌的抑菌圈直径都在20 mm以上,显著大于阿散酸与TMP的混合物(P＜0.05);阿散酸-TMP对埃希氏大肠杆菌、金黄色葡萄球菌、鸡白痢沙门氏菌、福氏志贺氏菌、藤黄微球菌的MIC分别为32、64、256、32、128 μg/mL,均小于阿散酸与TMP的混合物。阿散酸-TMP对供试菌的抑菌效果好于阿散酸、TMP及阿散酸与TMP的混合物。     

Efficacy of trimethoprim-sulfadoxine against Escherichia coli in a tissue cage model in calves

Tissue cages implanted subcutaneously in calves were infected with Escherichia coli. Twenty-four hours later, the calves were treated either with single doses of 2.5 + 12.5 or 5 + 25 mg/kg trimethoprim (TMP) + sulfadoxine (SDX) or with five doses of 7.5 + 37.5 mg/kg TMP + SDX at 12-h intervals. In addition, one cage in each of three calves in the highest dose group was infected 3 h after initiation of treatment. Untreated calves were kept as controls. Concentrations of TMP and SDX in plasma and tissue cage fluid (TCF) and counts of viable bacteria in TCF were determined. In the highest dose group, concentrations of TMP in TCF remained above the minimum inhibitory concentration of the test strain for 94-101 h and peak to minimum inhibitory concentration (MIC) ratio was close to 10. In spite of this, an effect of treatment was noted only in cages infected after initiation of treatment. In vitro studies and analysis of thymidine content in serum and TCF from calves suggest that levels of thymidine in TCF are high enough to antagonize the antibacterial effect of TMP. The results indicate that soft tissue infections in secluded infection sites of calves are refractory to treatment with TMP + SDX.     

P10B抗菌肽和硫酸小檗碱对肉鸡源大肠杆菌的体外联合抗菌作用研究

为了解P10B抗菌肽与硫酸小檗碱联合抗菌作用,进行P10B抗菌肽与硫酸小檗碱联用的体外抑菌试验。试验菌株为20株肉鸡源大肠杆菌菌株。采用微量肉汤稀释法测定P10B与硫酸小檗碱对大肠杆菌的最低抑菌浓度;棋盘稀释法测定两个药的分级抑菌浓度指数,判断联合抗菌效果。结果表明,在联合药敏试验中,两药呈协同作用的占10%,呈相加作用的占85%,呈无关作用的占5%。平均分级抑菌浓度指数为0.825,两种药联和用药效应主要表现为累加作用。     

Serum and skin concentrations after multiple-dose oral administration of trimethoprim-sulfadiazine in dogs.

Six healthy adult mixed breed dogs were each given 5 oral doses of trimethoprim (TMP)/sulfadiazine (SDZ) at 2 dosage regimens: 5 mg of TMP/kg of body weight and 25 mg of SDZ/kg every 24 hours (experiment 1) and every 12 hours (experiment 2). Serum and skin concentrations of each drug were measured serially throughout each experiment and mean serum concentrations of TMP and SDZ were determined for each drug for 24 hours (experiment 1) and 12 hours (experiment 2) after the last dose was given. In experiment 1, mean serum TMP concentration was 0.67 +/- 0.02 micrograms/ml, and mean skin TMP concentration was 1.54 +/- 0.40 micrograms/g. Mean serum SDZ concentration was 51.1 +/- 12.2 micrograms/ml and mean skin SDZ concentration was 59.3 +/- 9.8 micrograms/g. In experiment 2, mean serum TMP concentration was 1.24 +/- 0.35 micrograms/ml and mean skin TMP concentration was 3.03 +/- 0.54 micrograms/g. Mean serum SDZ concentration was 51.6 +/- 9.3 micrograms/ml and mean skin SDZ concentration was 71.1 +/- 8.2 micrograms/g. After the 5th oral dose in both experiments, mean concentration of TMP and SDZ in serum and skin exceeded reported minimal inhibitory concentrations of TMP/SDZ (less than or equal to 0.25/4.75 micrograms/ml) for coagulase-positive Staphylococcus sp. It was concluded that therapeutically effective concentrations in serum and skin were achieved and maintained when using the manufacturer's recommended dosage of 30 mg of TMP/SDZ/kg (5 mg of TMP/kg and 25 mg of SDZ/kg) every 24 hours.     

Repeated administration of trimethoprim/sulfadiazine in the horse--pharmacokinetics, plasma protein binding and influence on the intestinal microflora

Six healthy adult horses were given repeated administrations of trimethoprim/ sulfadiazine (TMP/SDZ) intravenously (i.v.) (2.5 mg/kg TMP and 12.5 mg/kg SDZ) and orally (p.o.) as a paste (5 mg/kg TMP and 25 mg/kg SDZ). Both formulations were given twice daily for 5 days, with a 3-week interval between i.v. and oral administration. The influence of the drug combination on the intestinal microflora was examined and the plasma concentrations, pharmacokinetic parameters and plasma protein binding were determined. There were no major changes in the bacterial intestinal flora and no clinical evidence of gastrointestinal disturbances following the i.v. and oral TMP/SDZ administration. An initial reduction in the number of coliform bacteria during the treatment was notable, though with no evident difference between i.v. and oral treatment. The minimum concentration during a dose interval at steady state (Cminss), the elimination half-life (t1/2beta) and the mean residence time (MRT) were significantly greater after oral administration compared to i.v. for both TMP and SDZ. The plasma protein binding was measured to be 20% for SDZ and 35% for TMP. Oral administration of TMP/SDZ in a dose of 30 mg/kg given twice daily in the form of paste appeared as a satisfactory method for obtaining plasma levels above MIC (minimum inhibitory concentration in vitro) values during the interdosing interval.     

甲氧苄啶对蒲公英体外抗菌增效作用的研究

采用微量棋盘稀释法测定了蒲公英、甲氧苄啶及两药联用对金黄色葡萄球菌、大肠杆菌和沙门氏菌的最小抑菌浓度(MIC),计算蒲公英与甲氧苄啶联用的组分抑菌浓度(FIC)指数。结果表明,蒲公英与甲氧苄啶联用对金黄色葡萄球菌、大肠杆菌和沙门氏菌的FIC指数分别为0.75、0.75和1,呈相加作用。采用平板计数的方法,测定了蒲公英与甲氧苄啶联用作用于3种细菌1、2、4和8 h后的细菌数,并计算杀菌率。利用最小二乘法对杀菌率进行拟合,计算出甲氧苄啶增强蒲公英体外抗金黄色葡萄球菌、大肠杆菌和沙门氏菌作用的最优添加剂量分别为4.0、1.8和2.0 mg/g。