阿莫西林、舒巴坦联用对鸭实验性大肠杆菌病的疗效试验

用试管两倍稀释法测定了阿莫西林、阿莫西林与舒巴坦联合对大肠杆菌的体外抗菌活性,并观察阿莫西林与舒巴坦联合治疗耐阿莫西林大肠杆菌诱发的鸭大肠杆菌病的效果。结果表明:阿莫西林与舒巴坦联合对鸭大肠杆菌产酶菌株体外抗菌活性优于阿莫西林,表现为明显的体外协同作用。阿莫西林与舒巴坦联用治疗耐阿莫西林大肠杆菌诱发的鸭大肠杆菌病,按10mg/kg体重(以阿莫西林量计算)肌肉注射,阿莫西林与舒巴坦联用1∶1和2∶1的有效率、治愈率分别为92.5%、92.5%和85%、80%,均显著高于感染对照组、阿莫西林饮水组及阿莫西林肌肉注射组(P<0.01)。     

Amoxicillin—current use in swine medicine

Amoxicillin has become a major antimicrobial substance in pig medicine for the treatment and control of severe, systemic infections such as Streptococcus suis. The minimum inhibitory concentration 90% (MIC 90) is 0.06 μg amoxicillin/ml, and the proposed epidemiological cut‐off value (ECOFF) is 0.5 μg/ml, giving only 0.7% of isolates above the ECOFF or of reduced susceptibility. Clinical breakpoints have not been set for amoxicillin against porcine pathogens yet, hence the use of ECOFFs. It has also been successfully used for bacterial respiratory infections caused by Actinobacillus pleuropneumoniae and Pasteurella multocida. The ECOFF for amoxicillin against A. pleuropneumoniae is also 0.5 μg/ml demonstrating only a reduced susceptibility in 11.3% of isolates. Similarly, P. multocida had an ECOFF of 1.0 μg/ml and a reduced susceptibility in only 2.6% of isolates. This reduced susceptibility disappears when combined with the beta‐lactamase inhibitor, clavulanic acid, demonstrating that it is primarily associated with beta‐lactamase production. In contrast, amoxicillin is active against Escherichia coli and Salmonella species but using ECOFFs of 8.0 and 4.0 μg/ml, respectively, reduced susceptibility can be seen in 70.9% and 67.7% of isolates. These high levels of reduced susceptibility are primarily due to beta‐lactamase production also, and most of this resistance can be overcome by the combination of amoxicillin with clavulanic acid. Currently, amoxicillin alone is considered an extremely valuable antimicrobial in both human and animal medicine and remains in the critically important category of antibiotics alongside the fluoroquinolones and macrolides by the World Health Organization as well as the third‐ and fourth‐generation cephalosporins, but these cephalosporins show marked resistance to basic beta‐lactamase production and are only destroyed by the extended‐spectrum beta‐lactamases. Amoxicillin alone and in combination with clavulanic acid are currently classed together in Category 2 in the European Union. By reviewing the pharmacodynamic data and comparing this with pharmacokinetic data from healthy and infected animals and clinical trial data, it can be seen that the product has a good efficacy against S. suis and A. pleuropneumoniae, in spite of usage over many years. However, it may be much less efficacious on its own against E. coli, due to reduced susceptibility and resistance associated with beta‐lactamase production, which is largely overcome by the use of clavulanic acid. It is felt that this differentiation may be useful in future classification of amoxicillin alone, in comparison with its combined use with clavulanic acid and thereby preserve the use of the more critically important antibiotics in veterinary medicine and reducing the risk of their resistance being transmitted to human.     

Pharmacokinetics of Amoxicillin Trihydrate in Desert Sheep and Nubian Goats

The pharmacokinetics of amoxicillin were studied in five Desert sheep and five Nubian goats after intravenous (i.v.) or intramuscular (i.m.) administration of a single dose of 10 mg/kg body weight. Following i.v. injection, the plasma concentration-versus-time data were best described by a two-compartment open model. The kinetic variables were similar in both species except for the volume of the central compartment (V_c), which was larger in sheep (p<0.05). Following i.m. injection, except for the longer half-life time of absorption in goats (p<0.05), there were no significant differences in other pharmacokinetic parameters between sheep and goats. The route of amoxicillin administration had no significant effect on the terminal elimination half-life in either species. The bioavailability of the drug (F) after i.m. administration was high (>0.90) in both species. These results indicate that the pharmacokinetics of amoxicillin did not differ between sheep and goats; furthermore, because of the high availability and short half-life of absorption, the i.m. route gives similar results to the i.v. route. Therefore, identical intramuscular and intravenous dose regimens should be applicable to both species.     

Antibiotic Resistance in two Water Reclamation Systems for Space Applications

The purpose of this research was to evaluate the antibiotic resistance in two water reclamation systems developed from space missions. The first system is a small-scale water reclamation system operated at Johnson Space Center designed to reclaim wastewater during long-term space missions. The second system was a scaled-down version of the Johnson Space Center system operated at Texas Tech University. Antibiotic resistance patterns to 10 antibiotics were investigated before and after controlled doses of amoxicillin were added to the water reclamation systems. The results of this study indicate that bacteria in all systems were resistant to many antibiotics including beta-lactam antibiotics and a beta-lactam, beta-lactamase inhibitor combination, amoxicillin with clavulanic acid.     

复方阿莫西林纳米乳的高效液相色谱分析及有效期研究

利用高效液相色谱仪建立测定复方阿莫西林纳米乳(AMX-LH-NE)中阿莫西林(AMX)和盐酸左氧氟沙星(LH)两种主药含量的高效液相色谱(HPLC)分析方法,并确定该药物的有效期。结果表明,AMX和LH分别在0.5～50μg/mL和5～60μg/mL浓度范围内线性关系良好;平均回收率为(99.27±1.26)%和(99.65±1.51)%,相对标准偏差(RSD)为1.27%和1.52%;平均保留时间为(10.22±0.13)min和(7.15±0.13)min;日内精密度RSD为1.56%和1.75%,日间精密度RSD为2.46%和2.62%。AMX-LH-NE的有效期为20个月。建立的HPLC分析方法专属性好,回收率、重复性和精密度高,可用于AMX-LH-NE制剂的主药含量测定及其质量控制。     

对12批市售阿莫西林产品监察结果的思考

对市售12批阿莫西林产品进行监督检查,结果含量均不符合规定,并存在企业伪造GMP证、套用兽药产品批准文号、擅自使用未批准的商品名等违规现象.本文从兽药产品文号、主要成分含量、成分、标签和说明书等方面分析产生的原因,并提出了加强管理的意见.     

阿莫西林在藏系羊体内的药物动力学研究

为研究阿莫西林在藏系羊体内的药物动力学特征,了解阿莫西林在藏系羊体内的吸收、分布、转化及排泄规律,以期为牧区兽医临床用药提供依据。本试验选取8只成年藏系羊,阿莫西林口灌给药,不同时间点采集藏系羊血液,利用高效液相色谱法测定血浆中药物浓度。结果表明,阿莫西林经藏系羊口灌给药(15 mg/kg.B.W)后,其主要药动学参数为:t_(1/2α)为(0.773±0.097)h,t1/2ka为(0.156±0.021)h,t_(1/2β)为(3.787±0.973)h,AUC为(8.249±1.023)μg·h/m L,T_(max)为(0.497±0.036)h,C_(max)为(2.667±0.198)μg/m L。表明阿莫西林口灌给药后,在成年藏系羊体内吸收迅速,消除较快。     

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。     

高效液相色谱荧光法检测鸡组织中阿莫西林残留

建立了高效液相色谱荧光法检测鸡组织中阿莫西林（ AMO ）的残留量。鸡组织样品经磷酸二氢钠溶液提取,乙腈去蛋白,正己烷去脂肪,饱和二氯甲烷萃取,上清液经水杨醛在酸性条件下沸水浴衍生化。以0．01 mol／L 的磷酸二氢钾溶液和乙腈溶液为流动相,梯度洗脱,流速为1 mL／min,高效液相色谱荧光检测,激发波长为358 nm,发射波长为440 nm。阿莫西林在25～1000μg／kg质量浓度范围内,线性关系良好。当阿莫西林添加水平为13～125μg／kg时,鸡组织中AMO的平均回收率在72．82％～88．82％,相对标准偏差在6．21％～9．63％;检测限、定量限分别为5μg／kg（S／N≥3）、13μg／kg（S／N≥10）。该方法操作简便,可适用于鸡组织中阿莫西林的提取和检测,且准确度和精密度均符合残留分析的要求。     

Evaluation of the ability of colistin,amoxicillin (components of Potencil®), and fluoroquinolones to attenuate bacterial endotoxin‐ and Shiga exotoxin‐mediated cytotoxicity—In vitro studies

Escherichia coli is one of the major pathogens in humans and animals causing localized and systemic infections, which often lead to acute inflammation, watery diarrhea, and hemorrhagic colitis. Bacterial lipopolysaccharide (LPS) and Shiga exotoxins (Stx) are mostly responsible for such clinical signs. Therefore, highly effective treatment of E. coli infections should include both eradication of bacteria and neutralization of their toxins. Here, for the first time, we compared the in vitro ability of common antibiotics to decrease LPS‐ and Stx‐mediated cytotoxicity: colistin, amoxicillin (used separately or combined), enrofloxacin, and its metabolite ciprofloxacin. Three experimental scenarios were realized as follows: (a) the direct effect of antibiotics on endotoxin, (b) the effect of antibiotic treatment on LPS‐mediated cytotoxicity in an experiment mimicking “natural infection,” (c) the effect of antibiotics to decrease Stx2e‐mediated cytotoxicity. Two cell lines, A549 and Vero cells, were used to perform cytotoxic assays with the methyl tetrazolium (MTT) and lactate dehydrogenase leakage (LDH) methods, respectively. Colistin and amoxicillin, especially used in combination, were able to attenuate LPS toxic effect, which was reflected by increase in A549 cell viability. In comparison with other antibiotics, the combination of colistin and amoxicillin exhibited the highest boster or additive effect in protecting cells against LPS‐ and Stx2e‐induced toxicity. In summary, in comparison with fluoroquinolones, the combination of colistin and amoxicillin at concentrations similar to those achieved in plasma of treated animals exhibited the highest ability to attenuate LPS‐ and Stx2e‐mediated cytotoxicity.