【作者】 王付民；

【导师】 胡功政；

【作者基本信息】 河南农业大学 ， 基础兽医学， 2003， 硕士

【摘要】 本论文的主要内容包括：最小抑菌浓度及最小杀菌浓度的测定、杀菌曲线的测定、抗菌后效应的测定及体内防治试验。 体外抑菌试验结果表明：头孢噻呋对各种标准及临床菌株的MIC均较小；其对G~+菌的抗菌活性略弱于氨苄西林，但对G~-菌的MIC远远低于氨苄西林；另外，头孢噻呋对G~+菌的抗菌活性强于头孢曲松，对G~-菌的抗菌活性要略弱于头孢曲松。杀菌曲线的结果表明：头孢噻呋等对4种标准株的杀菌速率均较大；与氨苄西林相比，头孢噻呋的各个浓度对金黄色葡萄球菌、猪链球菌的杀菌速率较小，但其各个浓度对鸡大肠杆菌、鸡白痢沙门氏菌的杀菌速率均大于氨苄西林的各个浓度；头孢噻呋与头孢曲松的各个浓度相比较，对4种标准菌株的杀菌速率差异均不显著；另外，头孢噻呋对4种菌株的杀菌速率均不随浓度的增加而增大。体外抗菌后效应的研究结果表明：头孢噻呋等3种β-内酰胺类抗生素对金黄色葡萄球菌、猪链球的PAE随着药物浓度的增加而延长，呈明显的浓度依赖性；其中氨苄西林的各个浓度对金黄色葡萄球菌、猪链球菌产生的PAE与相同浓度的头孢噻呋相比较差异显著；头孢噻呋与头孢曲松的各个浓度对金黄色葡萄球菌、猪链球菌产生的PAE相比差异不显著；头孢噻呋等在各个浓度对鸡大肠杆菌、鸡白痢沙门氏菌的PAE较短或为负值，表明它们对鸡大肠杆菌、鸡白痢沙门氏菌的PAE均为非浓度依赖性。头孢噻呋的体内防治的试验结果显示：头孢噻呋的防治效果优于头孢曲松与氨苄西林；其中头孢噻呋高、中剂量相比疗效相当；其中剂量与低剂量相比 疗效差异极其显著；头抱唾吱的高、中剂量与头泡曲松、氨芋西林的 疗效相比差异显著或极其显著；因此，头抱暖味的中剂量能起到较好。的防治该病的效果。更多还原

【Abstract】 This paper studied the pharmacodynamics of Ceftiofur and other B-lactam (Ceftriaxone and Ampicillin) antibiotics . The content of the studies included four parts: the minimal inhibitory concentrations (MICs) and minimal bactericidal (MBCs) to many clinical and standard strains, the killing-curves to four standard strains (E.coli, S.pullorum,S.aureus, S.suis),the post-antibiotic effects (PAEs) to four standard strains (E.coli, S.pullorum, S.aureus, S.suis), the therapeutic experiment (prevention and cure) in vivo using S.pullorum infection models.The results of antimicrobial susceptibility in vitro showed that Ceftiofur was a broad-spectrum Cephalosporin with potent activity against all kinds of clinical and standard strains; To the standard strains, the MICs was in the range of 0.00625-0.8 g/ml, and to the clinical strains, the MIC50 (the MIC of antibiomic that inhibits 50% of strains tested) and MIC% (the MIC of antibiomic that inhibits 90% of strains tested) were low, and respectively, the MIC50 and MIC90 were in the range of 0.24-4.2 g/ml, 0.6-11 g/ml; Which also indicated that Ceftiofur had better activity against gram-negative bacteria (G~ bacteria) and lower activity against gram-positive bacteria (G+ bacteria) than Ampicillin; In addition, the antimicrobial susceptibility showed that all kinds of bacteria produced high resistance to Ampicillin, however, Ceftiofur had good activity against these clinical strains. The results of killing-curves to four standard strains indicated that Ceftiofur and other B-lactam antibiotics (Ceftriaxone and Ampicillin) had higher killing rates; Thereinto, Ampicillin (8MIC, 5MIC, 2MIC) had higher killing rates to S. aureus and S. suis than Ceftiofur; on the reverse, Ceftiofur (8MIC, 5MIC, 2MIC) had higher killing rates to E. coli and S. pullorum than Ampicillin. Moreover, Ceftiofur and Ceftriaxone (8MIC, 5MIC, 2MIC) had the similar killing rates and killing-curves to four standard strains (P>0.05). Besides, the killing rates of Ceftiofur, Ceftriaxone, and Ampicillin weren’t positively correlative with the drug concentrations (8MIC,5MIC,2MIC) (P>0.05), as well as that they were antibiotics that didnt depend on drug concentration. In in-vivo PAE study, the results showed that, to S. aureus and S. suis, the PAEs of ceftiofur and other B-lactam antibiotics (Ceftriaxone and Ampicillin) were positively correlative with the drug concentrations (8MIC, 5MIC, 2MIC) (P<0.05); Obviously, to S. aureus and S. suis, Ampicillin had a longer PAEs than Ceftiofur (P<0.05), approximately, which was in the range of 0.4-0.7 hour; But, to E. coli and S. pullorum, all the drugs (including Ceftiofur) had short or negative PAE (<0.3h <0h), which indicated that the PAEs of all the drugs weren’t positively correlative with the drug concentrations(P>0.05).In in-vivo therapeutic experiment using S. pullorum infection models, the therapeutic effects of Ceftiofur were better than Ceftriaxone and Ampicillin. Thereinto, the high dose (0.2mg) of Ceftiofur had the similar therapeutic effects with the middle dose of Ceftiofur (0.1mg) (P>0.05), respectively, their healing rate was 86.7%>83.3%, and their effective rate was 93.3%, 90%; Otherwise, it’s low dose had bad therapeutic effects than the middle dose, their healing rate was 83.3%, 53.3%, and their effective rate was 90% , 66.7%, respectively; But, to Ceftriaxone and Ampicillin, the therapeutic effects of Ceftiofur (the middle dose) were obvious (P<0.05 or P<0.01); According to the result of prevention experiments in-vivo, to Ceftriaxone and Ampicillin, the middle dose of Ceftiofur could effectively prevent the disease(the effective rate was 80.0%, 63.3%, 33.3%). So, the prevention and cure experiment in vivo showed that Ceftiofur had potent advantage as a animal drug, and the middle dose (0.1 mg) of ceftiofur could prevent and cure the disease.更多还原