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中药提取物恢复耐药大肠杆菌对氨基糖苷类药物敏感性的研究 总被引：1，自引：0，他引：1
为考察五倍子、黄芩、黄连、艾叶、鱼腥草5种中药提取物恢复耐药大肠杆菌对氨基糖苷类抗生素敏感性的作用,采用1/2 MIC中药提取物对耐药菌株进行耐药性消除,通过影印培养法筛选出耐药性消除菌落,观察耐药消除率和消除子MIC值变化,并检测质粒及耐药基因rmt B的携带情况。结果表明:5种中药提取物对耐药大肠杆菌均有一定的抑制作用,耐药菌经1/2 MIC作用48 h后,五倍子、黄芩、黄连、艾叶、鱼腥草的耐药消除率分别为20.67%、21.33%、17.33%、16.67%、9.33%;消除子对庆大霉素(GEN)、卡那霉素(KAN)、阿米卡量(AMK)、新霉素(NEO)的MIC值均由高度耐药(512μg/m L)降至敏感(2~4μg/m L);5种中药提取物不能使耐药菌质粒丢失,却能导致耐药基因rmt B丢失。5种中药提取物可能是通过使高度耐氨基糖苷类药物的细菌丢失耐药主效基因来恢复对药物敏感性的。 相似文献
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为探究绿原酸对鸡源抗生素耐药大肠杆菌抑菌及耐药消除的作用机制，以影印法分离绿原酸浓度为1.25 mg/mL（亚抑菌浓度，1/2 MIC）的LB肉汤培养的第3代禽源大肠杆菌耐药逆转菌株，以微板法测定耐药逆转菌株的左氧氟沙星最小抑菌浓度（MIC），并进一步通过转录组测序方法分析绿原酸消除大肠杆菌耐药性的分子机制。结果显示：耐药逆转菌株对左氧氟沙星的MIC由16 μg/mL降低至4~8 μg/mL，说明1.25 mg/mL的绿原酸可在一定程度上消除耐药大肠杆菌的左氧氟沙星耐药性。为进一步解析绿原酸对鸡源大肠杆菌耐药消除作用的分子机制，通过转录组测序方法对耐药性消除前后鸡源大肠杆菌基因表达水平进行对比分析发现：绿原酸作用后共有12个基因的表达量发生显著下调，通过荧光定量PCR验证结果基本一致。经过GO功能富集分析和KEGG代谢通路富集分析发现，差异表达基因在功能上集中于膜组成成分和DNA重组，在代谢通路富集中差异基因均与代谢相关，差异基因中bhsA、cysP为Coli-HB染色质转录RNA（GenBank登录号：CP020933），oqxA、oqxR、emaA、pinR、xerD、folA、repA、repC、adhP、IS26为Coli-HB质粒1转录RNA（GenBank登录号：CP020934）。从差异表达基因的分布可以看出，绿原酸可以抑制细菌DNA重组、使细菌抗逆性减弱、抑制耐药基因活性等，在一定程度上消除大肠杆菌的左氧氟沙星耐药性，起到抑菌及耐药消除作用。 相似文献
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临床获得1株鸡致病性大肠杆菌CE01，进行药每、质粒转化、耐药质粒消除试验，结果该菌对11种受试抗菌药物全部呈高度耐药，其中氧氟沙星的MIC≥50μg/ml，且含有喹诺酮抗生质粒，溴化乙淀和黄连素作为消除剂作用48小时可使其喹诺酮抗性质粒消除，耐药水平显著下降。聚合酶链反应（PCR）扩增该菌gyrA基因喹诺酮耐药决定区（QRDR），质粒DNA和染色体DNA均可扩增出长度为668bp的PCR产物片段。经测序分析，两者基因序列相同率为98.17%，相同位点突变相同的碱基有5个，相同位点突变不同的碱基有2个；与基因数据库Swanberg等报道的大肠杆菌gyrA基因相应序列比较，该菌质粒DNA PCR产物同源率97.8%，有13个位点发生突变，3个氨基酸被替换；染色体DNA PCR产物同源率98%，有12个位点发生突变，2个氨基酸被替换。用放射性同位素α-^32P分别标记CE01菌株染色体DNA和质粒DNA的PCR扩增片段制备探针，对CE01菌株进行检测。质粒DNA和染色体DNA分别与质粒控针和染色体探针杂交出现典型的阳性杂交斑。证实该菌株质粒和染色体上同时存在耐喹诺酮gyrA突变基因，对喹诺酮的耐药性是质粒介导和染色体突变共同作用的结果。 相似文献
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经药敏试验测定,复方苍术口服液和复方十大功劳颗粒对5株耐药大肠杆菌无抑菌活性。但将其加入耐恩诺沙星大肠杆菌的肉汤培养基中进行传代,连传7代后,发现3株菌株的MIC降低了8倍以上,耐药逆转率为60%。其中2号菌株GyrA基因83位氨基酸突变为正常的氨基酸序列,3号菌株ParC基因80位氨基酸也有原来的氟喹诺酮耐药性突变状态转变为正常状态。结果表明中药制剂能逆转大肠杆菌的耐药性。 相似文献
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为探明泰州地区鸡源大肠杆菌产超广谱β-内酰胺酶(ESBLs)情况及耐药情况,对13株分离自泰州地区的鸡源大肠杆菌进行ESBLs检测,并采用微量肉汤稀释法测定不同药物对产ESBLs菌和非产ESBLs菌的最小抑菌浓度(MIC).结果显示,13株分离菌中有5株被确定为产ESBLs菌株,阳性率为38.5%.产ESBLs菌对β-内酰胺类抗菌药的耐药性极其严重,耐药率明显高于非产ESBLs菌,二者对氨苄西林的耐药率分别为100%和62.5%,对头孢噻呋的耐药率分别为100%和12.5%,对头孢曲松的耐药率分别为80%和20%,产ESBLs菌对其他抗菌药物的耐药率也明显高于非产ESBLs菌.氨苄西林与舒巴坦(2:1)联用与单用氨苄西林相比,对产ESBLs菌的MIC值降低至单用氨苄西林时的1/16~1/8,但对非产ESBLs菌的MIC值没有明显变化.氨苄西林与阿米卡星(1:1)联用与单用两者中的任何一种相比,对产ESBLs菌和非产ESBLs菌的MIC值均降低至单药时的1/16~1/2.结果表明,临床可选择β-内酰胺酶类抗生素与β-内酰胺酶抑制剂的混合制剂来治疗产ESBLs鸡大肠杆菌的感染,也可尝试将不同种类、不同作用机理药物联合应用来治疗鸡大肠杆菌感染,尤其是耐药性鸡大肠杆菌感染. 相似文献
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为了了解内蒙古地区腹泻犊牛中大肠杆菌的污染状况、耐药情况及蒲公英水煎液对多重耐药大肠杆菌耐药性的消除作用。本试验采用革兰染色、生化试验和PCR方法对采集到的107份犊牛源病料进行大肠杆菌的分离和鉴定,采用K-B法检测分离菌株对18种抗菌药物的敏感性,采用PCR方法进行8种耐药基因的检测,采用琼脂稀释法测定蒲公英水煎液对分离菌株的最小抑菌浓度(MIC),通过将菌株与蒲公英水煎液作用后进行耐药消除试验。结果显示,从107份病料中分离鉴定出44株犊牛源大肠杆菌,分离率为41%;大肠杆菌分离株对氨苄西林、头孢噻吩、头孢噻肟、环丙沙星和左氧氟沙星5种抗菌药物的耐药率均达到50%以上;β-内酰胺类耐药基因中blaCTX-M基因携带率为86%,喹诺酮类耐药基因中qnr(S)基因携带率为32%;蒲公英水煎液对筛选出的耐药菌株的MIC为200 mg/mL;经蒲公英水煎液处理后的大肠杆菌对抗菌药物的敏感性增强,而且更不容易出现耐药。结果表明,内蒙古地区腹泻犊牛中大肠杆菌的耐药情况严重,而蒲公英水煎液对大肠杆菌的多重耐药有一定的消除作用,可降低临床应用抗菌药物的耐药性,增加临床疗效,本... 相似文献
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对动物源大肠杆菌采用二倍稀释法对氨基糖苷类药物及其他药物进行了MIC的测定,结果显示对十种西药全部耐药。应用1/2MIC的中药提取物对耐药菌株进行了耐药性消除的初步探索研究,结果表明临床多重耐药大肠杆菌用中药提取物作用24代以后,地锦草提取物耐药消除最强,三黄汤提取物次之,对某些氨基糖苷类药物的MIC明显下降。另外,对消除前后的细菌提取质粒,扩增氨基糖苷类的耐药基因,发现随着MIC的降低,耐药基因的数量也不同程度地减少和消失。由此可见地锦草等中药提取物对可移动的耐药基因元件有一定的消除作用,对耐药基因的扩散有抑制作用。 相似文献
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Pharmacokinetics of ceftriaxone after intravenous, intramuscular and subcutaneous administration to domestic cats 总被引：2，自引：0，他引：2
Albarellos GA Kreil VE Landoni MF 《Journal of veterinary pharmacology and therapeutics》2007,30(4):345-352
The pharmacokinetic properties of ceftriaxone, a third-generation cephalosporin, were investigated in five cats after single intravenous, intramuscular and subcutaneous administration at a dosage of 25 mg/kg. Ceftriaxone MICs for some gram-negative and positive strains isolated from clinical cases were determined. Efficacy predictor (t > MIC) was calculated. Serum ceftriaxone disposition was best fitted by a bicompartmental and a monocompartmental open models with first-order elimination after intravenous and intramuscular and subcutaneous dosing, respectively. After intravenous administration, distribution was fast (t1/2d 0.14 +/- 0.02 h) and moderate as reflected by the volume of distribution (V(d(ss))) of 0.57 +/- 0.22 L/kg. Furthermore, elimination was rapid with a plasma clearance of 0.37 +/- 0.13 L/h.kg and a t1/2 of 1.73 +/- 0.23 h. Peak serum concentration (Cmax), tmax and bioavailability for the intramuscular administration were 54.40 +/- 12.92 microg/mL, 0.33 +/- 0.07 h and 85.72 +/- 14.74%, respectively; and for the subcutaneous route the same parameters were 42.35 +/- 17.62 microg/mL, 1.27 +/- 0.95 h and 118.28 +/- 39.17%. Ceftriaxone MIC for gram-negative bacteria ranged from 0.0039 to >8 microg/mL and for gram-positive bacteria from 0.5 to 4 microg/mL. t > MIC was in the range 83.31-91.66% (10-12 h) of the recommended dosing interval (12 h) for Escherichia coli (MIC90 = 0.2 microg/mL). 相似文献
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The pharmacokinetic properties of ceftazidime, a third generation cephalosporin, were investigated in five cats after single intravenous (IV) and intramuscular (IM) administration at a dose rate of 30 mg/kg. Minimum inhibitory concentrations (MICs) of ceftazidime for some Gram-negative (Escherichia coli, n=11) and Gram-positive (Staphylococcus spp., n=10) strains isolated from clinical cases were determined. An efficacy predictor, measured as the time over which the active drug exceeds the bacteria minimum inhibitory concentration (T>MIC), was calculated. Serum ceftazidime disposition was best fitted by a bi-compartmental and a mono-compartmental open model with first-order elimination after IV and IM dosing, respectively. After IV administration, distribution was rapid (t(1/2(d)) 0.04+/-0.03 h), with an area under the ceftazidime serum concentration:time curve (AUC((0-infinity))) of 173.14+/-48.69 microg h/mL and a volume of distribution (V((d(ss)))) of 0.18+/-0.04 L/kg. Furthermore, elimination was rapid with a plasma clearance of 0.19+/-0.08 L/hkg and a t(1/2) of 0.77+/-0.06 h. Peak serum concentration (C(max)), T(max), AUC((0-infinity)) and bioavailability for the IM administration were 89.42+/-12.15 microg/mL, 0.48+/-0.49 h, 192.68+/-65.28 microg h/mL and 82.47+/-14.37%, respectively. Ceftazidime MIC for E. coli ranged from 0.0625 to 32 microg/mL and for Staphylococcus spp. from 1 to 64 microg/mL. T>MIC was in the range 35-52% (IV) and 48-72% (IM) of the recommended dosing interval (8-12h) for bacteria with a MIC(90)4 microg/mL. 相似文献
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The pharmacokinetics of marbofloxacin were investigated in healthy (n=8) and Mannheimia haemolytica naturally infected (n=8) Simmental ruminant calves following intravenous (i.v.) and intramuscular (i.m.) administration of 2 mg kg(-1) body weight. The concentration of marbofloxacin in plasma was measured using high performance liquid chromatography with ultraviolet detection. Following i.v. administration of the drug, the elimination half-life (t(1/2 beta)) and mean residence time (MRT) were significantly longer in diseased calves (8.2h; 11.13 h) than in healthy ones (4.6 h; 6.1 h), respectively. The value of total body clearance (CL(B)) was larger in healthy calves (3 ml min(-1) kg(-1)) than in diseased ones (1.3 ml min(-1) kg(-1)). After single intramuscular (i.m.) administration of the drug, the elimination half-life, mean residence time (MRT) and maximum plasma concentration (C(max)) were higher in diseased calves (8.0, 12 h, 2.32 microg ml(-1)) than in healthy ones (4.7, 7.4 h, 1.4 microg ml(-1)), respectively. The plasma concentrations and AUC following administration of the drug by both routes were significantly higher in diseased calves than in healthy ones. Protein binding of Marbofloxacin was not significantly different in healthy and diseased calves. The mean value for MIC of marbofloxacin for M. haemolytica was 0.1+/-0.06 microg ml(-1). The C(max)/MIC and AUC(24)/MIC ratios were significantly higher in diseased calves (13.0-64.4 and 125-618 h) than in healthy calves (8-38.33 and 66.34-328 h). The obtained results for surrogate markers of antimicrobial activity (C(max)/MIC, AUC/MIC and T > or = MIC) indicate the excellent pharmacodynamic characteristics of the drug in diseased calves with M. haemolytica, which can be expected to optimize the clinical efficacy and minimize the development of resistance. 相似文献
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为探讨饲料中添加刺五加提取物对肉鸡生长性能、屠宰性能及经济效益指标的影响,试验选择体重相近的21日龄白羽肉鸡400只,随机分成4组,每组10个重复,每个重复10只,1组为空白对照组饲喂基础日粮,试验2、3、4组分别在基础日粮中添加1.0%、2.0%、3.0%的刺五加提取物,预试验7 d,试验期为21 d。结果表明:(1)试验2、3、4组的平均日采食量均高于1组(P>0.05),试验3、4组的平均日增重较1组比分别提高11.8%、10.3%(P<0.05),料重比较1组比分别降低16.7%、15.0%(P<0.05);(2)试验2、3、4组的屠宰率、全净膛率、半净膛率均高于1组(P>0.05),验3、4组的胸肌率、腿肌率较1组比分别提高15.3%、14.0%、21.9%、15.1%(P<0.05);(3)试验3、4组每只肉鸡经济效益较1组比分别提高11.6%、10.6%。综上,饲料中不同水平的刺五加提取物添加均可以提高白羽肉鸡的生长性能、屠宰性能及经济效益,以2.0%添加为适宜。 相似文献
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文章旨在评估日粮添加不同酸化剂对断奶仔猪生长性能、免疫性能和微生物菌群的影响。试验将384头平均初始体重为(6.16±0.23)kg的21d断奶仔猪随机分为4组,每组6个重复,每个重复16头,各组断奶仔猪分别饲喂基础日粮、基础日粮+45mg/kg抗菌肽、基础日粮+4kg/T柠檬酸及基础日粮+3kg/T复合酸化剂,试验共进行4周。结果:与抗菌肽组相比,两个酸化剂处理组1~14d、15~28d及1~28d日采食量分别降低9.86%、13.88%,46.87%、50.88%和33.13%、37.01%(P<0.05),而15~28d和1~28d日增重显著降低49.73%、57.03%和31.38%、48.67%(P<0.05)。抗菌肽组和柠檬酸组1~28d料重比较对照组显著降低11.44%和13.43%(P<0.05)。柠檬酸组血清IgG浓度较抗菌肽组显著提高43.07%(P<0.05)。日粮添加单一或复合酸化剂使断奶后14d和28d猪粪中乳酸杆菌数量显著提高10.56%、8.94%和19.43%、18.17%(P<0.05),同时酸化剂组断奶后28d粪中芽孢杆菌数量分别显著提高21.45%和20.93%(P<0.05)。酸化剂处理组断奶后28d猪粪中大肠杆菌数量较对照组显著降低19.58%和26.28%(P<0.05),而断奶后14和28d粪中沙门氏菌数据显著降低了43.68%、46.44%和44.94%、47.64%(P<0.05)。结论:柠檬酸酸对饲料转化率有积极影响、增加有益菌数和血清IgG浓度,而复合酸化剂对生长性能参数有负面影响,对肠道菌群具有积极作用。 相似文献
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本试验旨在研究不同中药与盐酸恩诺沙星联用对大肠杆菌耐药菌株的体外抑菌作用。采用微量肉汤法测定临床上一种常用药物盐酸恩诺沙星和不同中药对大肠杆菌耐药菌株及其联合使用的最小抑菌浓度(minimum inhibitory concentration,MIC)。结果发现,单味中药水提物中侧柏叶、金樱子和五味子的抑菌效果较好,其MIC值分别为3.91、3.91和7.81 mg/mL;单味中药的醇提物中,侧柏叶、马齿苋抑菌效果较好,其MIC值分别为7.81和3.91 mg/mL。盐酸恩诺沙星分别与五味子和金樱子水提物联合作用后,对大肠杆菌耐药菌株的MIC值分别降低到0.0078和0.0039 mg/mL;与马齿苋、赤芍、侧柏叶和金樱子的醇提物联合后,对大肠杆菌耐药菌株MIC值均明显降低。盐酸恩诺沙星分别与鱼腥草水提物、赤芍水提物、椿皮水提物、马齿苋醇提物、苍术醇提物、三颗针醇提物、赤芍醇提物、薤白醇提物、拳参醇提物、侧柏叶醇提物、金樱子醇提物和败酱草醇提物联合作用后,对大肠耐药菌株呈现相加或协同抑菌作用,其FIC值分别为0.75、0.62、0.62、0.27、0.75、0.75、0.31、0.62、0.50、0.53、0.28和0.62。初步认为不同中药中含有能有效降低大肠杆菌耐药性的中药,也含有与盐酸恩诺沙星组合,具有协同或相加作用的中药,为寻找有效防治大肠杆菌病的药物组合来对抗多重耐药菌提供了可能。 相似文献
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Clinical pharmacology of apramycin in calves 总被引：3，自引：0，他引：3
G. ZIV A. BOR S. SOBAGK D. ELAD J. F. M. NOUWS 《Journal of veterinary pharmacology and therapeutics》1985,8(1):95-104
The minimal inhibitory concentrations (MIC) of apramycin, a unique aminocyclitol antibiotic, were compared with the MIC of dihydrostreptomycin and neomycin for 323 Salmonella, 178 Escherichia coli and twenty-six Pasteurella multocida isolates recovered from newborn calves. Apramycin exhibited better in vitro anti-bacterial activity than dihydrostreptomycin and neomycin; isolates of Salmonella group B and E. coli resistant to the latter were sensitive to apramycin. The two-compartment open model was appropriate for the analysis of serum apramycin concentrations measured after intravenous (i.v.) administration. The distribution half-life (t 1/2 alpha) of the drug was 28 min, the elimination half-life (t 1/2 beta) was 4.4 h, and the apparent volume of distribution (V1) and the distribution volume at steady state (Vdss) were 0.34 and 0.71 l/kg, respectively. The drug was quickly and completely absorbed after intramuscular (i.m.) injection; peak serum drug concentrations were directly related to the dose administered, they were obtained 1-2 h after treatment and the i.m. t 1/2 beta was 5 h. There was no evidence of drug accumulation in the serum after three daily i.m. injections at 20 mg/kg. More than 95% of the i.v. and i.m. doses were recovered in the urine within 96 h post-treatment but the cumulative percentage of drug recovery in the urine after oral treatment was 11%. The durations of free drug concentrations in the tissues after i.v. and i.m. injection were estimated from the serum drug level data, percent of serum protein binding, Vdss, t 1/2 beta, and the MIC. Computations showed that apramycin should be administered i.m. at 20 mg/kg every 24 h in order to maintain in tissues potentially effective drug concentrations sufficient to inhibit 50% of the Salmonella, E. coli, and P. multocida isolates, and at 12-h intervals to inhibit 90% of the isolates. 相似文献
19.
Pharmacokinetics of marbofloxacin in mature horses after single intravenous and intramuscular administration 总被引：4，自引：0，他引：4
Carretero M Rodríguez C San Andrés MI Forés P de Lucas JJ Nieto J Waxman S San Andrés MD González F 《Equine veterinary journal》2002,34(4):360-365
The pharmacokinetic behaviour of marbofloxacin, a new fluoroquinolone antimicrobial agent developed exclusively for veterinary use, was studied in mature horses (n = 5) after single-dose i.v. and i.m. administrations of 2 mg/kg bwt. Drug concentrations in plasma were determined by high performance liquid chromatography (HPLC) and data obtained were subjected to compartmental and noncompartmental kinetic analysis. This compound presents a relatively high volume of distribution (V(SS) = 1.17 +/- 0.18 l/kg), which suggests good tissue penetration, and a total body clearance (Cl) of 0.19 +/- 0.042 l/kgh, which is related to a long elimination half-life (t(1/2beta) = 4.74 +/- 0.8 h and 5.47 +/- 1.33 h i.v. and i.m. respectively). Marbofloxacin was rapidly absorbed after i.m. administration (MAT = 33.8 +/- 14.2 min) and presented high bioavailability (F = 87.9 +/- 6.0%). Pharmacokinetic parameters are not significantly different between both routes of administration (P>0.05). After marbofloxacin i.m. administration, no adverse reactions at the site of injection were observed. Serum CK activity levels 12 h after administration increased over 8-fold (range 3-15) compared with pre-injection levels, but this activity decreased to 3-fold during the 24 h follow-up period. Based on the value of surrogate markers to predict clinical success, Cmax/MIC ratio or AUC/MIC ratio, single daily marbofloxacin dose of 2 mg/kg bwt may not be effective in treating infections in horses caused by pathogens with an MIC > or = 0.25 microg/ml. However, if we use a classical antimicrobial efficacy criteria, marbofloxacin can reach a high plasma peak concentration and maintain concentrations higher than MICs determined for marbofloxacin against most gram-negative veterinary pathogens throughout the administration period. Taking into account the fact that fluoroquinolones are considered to have a concentration-dependent effect and a long postantibiotic effect against gram-negative bacteria, a dose of 2 mg/kg bwt every 24 h could be adequate for marbofloxacin in horses. 相似文献