头孢噻呋的药效学研究
|
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。
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.
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。
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.
引文
1. Robert B J, Yaneey RJ, Kinmey ML, et al. Ceftiofur Sodium, abroad-spectrum cephalosporin: Evaluation in vitro and vivo mice. Am J Vet ResVo148, No. July; 1050-1053.
2. Yancey RJ, Brown SA, Ceftiofur Sodium: antimicrobial activity of parent ceftiofur and metabolites. Acta Veterinaria Scandinavica, 1991, 87(suppl.): 95-97.
3. Shryock T R, White DW, Wemer CS, Antimicrobial Susceptibity of Moraxella bovis. Vet Microbial, 1998, 61(4): 305-309.
4. Soback TR, G. Ziv, Winkler M, et al. Pharmacokinetics of ceftiofur administered intravenously and intramuscularly to lactating cows. Israeli journal of ret ned, 1989(4): 118-123.
5. Watts J, Salmon SA, Yancey RJ, et al. Antimicrobial Susceptibity of microorganisms islated form mammany glands of diary heifers. Diary Sci., 1995(78): 1637-1648.
6. Folz S D, Hanson, B J, Griffin AK, et al. Treatment of respiratory infections in horses with ceftiofur sodium. Equine Veterinary journal, 1992(24):300-304.
7. Raemdonck D L, Tanner A C, Tolling ST, et al. Antimicrobial Susceptibity of Actinobacillus Pleuropneumoniae, pasteurella multocida and salmonella choleraesuis isolateds from pigs Vet, Rec, 1994, 134(1):5-7.
8. Dixon BA, Issvoran GS, The activity of ceftiofur sodium for aeromons spp. Isolated form omamental fish. J Wild Dis, 1992, 28(3): 453-456.
9. Salmon SA, Watts JL, Yancey RJ, In vitro activity of ceftiofur and its primary metaolite, deuroylceftiofur, against organisms of veterinary importance. J vet Diagno Invest, 1996, 8(3): 332-336.
10. Prem S Jalan, Thomas S, Arnold, Mavc F. Kubicek, Metabolism of ceftiofur. Nature of uriny and plasma metabolism in rats and cattle. Journal of agricultural and food chemistery, 1989, 37, 1110-1112.
11. Prem, S jaglan, Fred S Yein, Res E Homish, et al. Depletion of intramuscularly injected ceftiofur from the milk of diary cattle. 1992 J Diary Science 75:1870-1876.
12. Steven L Halsead, Robert D. walker, Pharmacokinetics of Ceftiofur in serum, Tissue, chamber fluid and bronchial secretions form healthy beef-bred cattles:Can J Vet Res 1992, 56, 267-274.
13. Brown SA, Chester S T, Robb EJ, et al. Effect of age on the pharmacokinectics of single dose ceftiofur sodium administered intramhsculary or intravenously to cattle. J Vet Pharmacol Ther. 11996, 19(1):32-38.
14. Jaglan PS, Roof RD, Yein FS, et al. Concentration of ceftiofur metabolites in plasma and lungs horses following intramuscular treament J Vet. Pharmacol. Ther. 17, 24-30, 1994.
15. Marry Ann Guglick, Charles G Macallister, Cyrill R Clarke, et al. Pharmacokinetics of cefepime and comparion with those of ceftiofur in horses, AJVR, Vol59.No.4 April 1998.
16. Meyer J C, Brown MB, Grownwall RR, et al. Pharmacokinetics of ceftiofur sodium in neohatal foals after intramuscular injection. Equine Vet J. 1992, 24, 485-486.
17. Cervantes CC, Brown MB, Grownwall RR, et al.. Pharmacokinetics of ceftiofur sodium in body fluids and endometrium after repeated intramuscular in mares, Am, J, Vet Res 1993, 54: 573-575.
18. Brown SA, Hanson BJ, Mionot A, et al. Comparison of plasma pharmacokinetics and bioaviability of ceftiofur sodium and ceftiofur hydrochloride in pigs after asingle intramuscular injection J vet pharmacol. Therap. 22, 35-40.
19. Courtin F, Graigmill AL, Wetzlich SE, et al. Pharmacokinetics of ceftiofur and metabolits after single intravenous and intramuscular administration and mutiple intramuscular admintration of ceftiofur sodium to dairy goats J vet pharmacol. Therap. 1997, 20 (5):368-373.
20. Caraigmill AL, Brown SA, Wetzlich SE, et al Courtin F, Graigmill AL, et al. Pharmacokinetics of ceftiofur and metabolits after single intravenous and intramuscular administration and mutiple intramuscular admintration of ceftiofur sodium to sheeo. J vet pharmacol. Therap. 1992, 19 (6):431-438.
21. Foreman JH, Hungerferd LL, Folz SD, et al. Ceftiofur sodium for the trementment of naturally-acquired respiratory tract infections in horses, Joural of Veterinary interal medivine(1993).
22. Kesler DJ, Bechtol DJ, Efficacy of sustained release needle-less ceftiofur sodium implants in treating calves with bovine respiratory disease J zentrabl veterinarmed, 1999, 46:25-35.
23. Navarre CB, Zhang, Sunkara G, et al. Ceftiofur distribution in plasma and joint fluid following regional limb injection in cattle. J vet. Pharmacol, therap. 22,13-19.
24. Wallgren P, Segall T, Segall T, et al. Experimental infections with actinobacillus pleuropeumoniae in pigs. comparion of five different parenteral antibiotic traments. Zntrabl veterinarined, 1999, 46(4):249-260.
25. Navarre CB, Zhang, Ceftiofur distribution in plasma and joint fuid following regional limb injection in cattle. J vet. Pharmacol, therap. 22, 13-19.
26. Wallgren P, Segall T, et al. Experimental infections with actinobacillus pleuropeumoniae in pigs. comparion of five different parenteral antibiotic traments Zntrabl veterinarined, 1999, 46(4): 249-260.
27. Dvidson RJ, Zhanel GG, et al. Human serum enhances the postantibiotic effect of fluoroqunolones against staphylococcusaures. Anticrobial agents and chemotherapy 1991, 6(35): 1261-1263.
28. Ellis LS, Benson CA, Postantibiotic effect of clarithromycin alone and combined with ethambutol against mycobacterium avium complex. Antimicrobial and chemotiherapy 12(39):2803-2806.
29. Watanabe T, Kanno M, Tejima E, et al.. Effects of macrolides on ultrastructure of staphylococcus aureus during postantibiotics phase Drugs Exptl Clin Res 1992, 18(3): 81-88.
30. FuurstedD, KnudsenJD, et, al. Comparative study of bactericidal activities, posteantibicotic effects, and effects on bacterial virulence of pencillin and six marcrolids against streptococcuspneumoniae. Antimicrobialandchemotiherapy, 1997, 8(41): 1693-96.
31. Gicquel M, SandersP, Posteantibicotic effects of enrofloxacin on respiratory pathogens in pigs: pasteurella multocida, bordetella bronchiseptica and actinobacillus pleuropneumoniae. J vet pharmacol therap 1997, 20: 21-86
32. Aeschlimann JR, Dresser LD, Effect of nora inhibitors on in vitro antibacterial activities and postantibiotic effects of levofloxacin, ciproxacin, and norfloxacin in genetically related strains of staphylococcus auresus. antimicrocial agents and chemotherapy. 1999, 2(43):335-340.
33. Elisabeth Lowdin, A new method to determine post -antibiotic-effects and effects ofsub-inhibitoryantibioticconcentration. antimicrocialagentsandchemotherapy, 1993, 37(10):2200-2205.
34. Odenholt I, Holm SE, et al. Effects of benzylpencillin on streptococcus pyogenes during the post-antibiotic phase in vitro J antimicrob. Chemother.. 1989, 24: 147-156.
35．方翼，王睿，3种氟喹诺酮类药物抗菌后效应的研究，中国抗生素杂志，1997，1(22)：67-70。
36．张烨，李家泰，新氨基糖苷类抗生素89-07抗生素后效应研究，中国抗生素杂志，6(20)：429-433。
37．朱汝锦 译，斯帕沙星和环丙沙星对绿脓杆菌和粪链球菌的体外抗生素后效应，国外医药抗生素分册，1995，16(6)：450-452。
38．方翼，王睿，斯帕沙星和洛美沙星的抗生素后效应，中国新药杂志，8(9)：608-610。
39．王志强，陈杖榴，兽用氟喹诺酮类药物在猪体内外抗菌后效应初报，畜牧兽医学报，2002，33(5)：477-481
40．胡功政，李敏，左旋氧氟沙星的药效学研究，华中农业大学学报，2002，21(2)130-134。
41．刘爱芳，李昌文等，单诺沙星对大肠杆菌和金黄色葡萄球菌的体外抗菌后效应，黑龙江畜牧与兽医，2002，(2)：6-8。
42．俞树荣，微生物和微生物学检验，人民卫生出版社，1997。
43．卢中华，催保安，兽医微生物学，河南科技出版社，1996。
44．崔风珍，鹿梅花，微生物学检验，人民卫生出版社，1993。
45．杨春生，临床检验学，天津科学技术出版社，1997。
46．戴自英，临床抗菌药物学，人民卫生出版社，1985。
47．庄景新，李泰兴，速解灵与马立克疫苗混合接种对鸡免疫效果观察，畜牧与兽医，30卷，1998第四期。
48．胡功政，张许科，沙拉沙星对鸡细菌病的药效学研究，中国预防兽医学报，2000，第22卷，第1期。
49．曾振灵，刘雅红，氧氟沙星对实验性鸡大肠杆菌病的药效学研究，中国兽医学报，1996，第16卷，第5期。
50．丁焕中，陈杖榴，兽用抗生素头孢噻呋的研究进展，中兽医医药杂志，2000，第4期。
51．王付民，胡功政，新的抗菌药-头孢噻呋，信阳高等专科学校学报，2001，第1期。
52．陈杖榴等，兽医药理学，中国农业出版社，2002，第二版。
53．宋振玉，刘耕陶，当代药理学，1994，第一版。
54．杨世杰，王怀良，药理学，人民卫生出版社，2001，第一版。
55．王睿，临床治疗手册，人民军医出版社，1994，第一版。
56. Johan W. Mouton, et al. Pharmacokinetics-pharmacodynamic modeling of activity of ceftazidime during continuous and intermittent infusion. Antimicrobial agents and chemotherapy, 1996, 41(4): 733-736.
57. Walliam A Craig., Interrelationship between pharmacokinetics and pharmacodynamics in determining dosage regiments for broad spectrum cephalosporins. Dign. Microbial infect. dis 1995, 22:89-96.
58. Frederic Fitoussi, Catherine Dort, Ana sandin, et al. Killing activity of cefpirome against penicillin-resistant streptococcus pneumoniae. in a pharmacodynamic model simulating the cerebrospinal fluid concentration profile. Antimicrob. Agents chemother, 1995, 39(11): 2560-2563.
59. Gudmundsson S, et al. J Antimicrobial agents and chemotherapy, 1993, (8): 149-152.
60．胡功政，李荣誉，新全实用兽药手册，河南科学技术出版社，2002，第二版。
61．李家泰主编，临床药理学，人民卫生出版社，1998，第二版。
62. Geoge GZ, et al Ann pharmacother 1991, 2(25): 153-158
63. Blandino G et al. Drugs Exp Clin Res, 1992, 18(8): 319-324
64．王睿，刘卫，氧氟沙星与哌拉西林单用或联合应用的抗生素后效应，中国抗生素杂志，1993，18(5)：383。
65. Rodald CL, et al. Pharmacodynamic modeling of bacterial kinetics: β-lactam antibiotics against eschrichia coli J pharmaceutical sciences, 1994, 970-975.
66. Vogelman BS, et al Ann Pharmacother, 1991, 2(25): 153.
67．徐玉红，张华安，抗菌素后效应及临床意义，中国医院药学杂志 1996，16(12)：543-544。
68．方翼，β-内酰胺类抗生素后效应研究概况，国外医药抗生素分册 1998，19(3)：231-236。
69. Hanberger H et al. Antimicrob Agents Chemother, 1990, 34:102.
70. Bush L M et al. Antimicrob Agents Chemother, 1998, 32:877.
71. Fuad N et al. Biochem J 1976, 155: 623.
72．王浴生，抗生素后效应及临床意义，中国抗生素杂志，1996，21(4)：306-315。
73．陈绣枢等，体外抗菌素后效应的方法学及临床金黄色葡萄球菌的研究，1991，临床检验杂志，1991，(2)：24-25。
74．鲍燕燕，抗菌素后效应，药学情报通讯，1989，7(4)：24-25。
75．董景之，抗菌素后效应，天津药学，1997，9(3)；12-16。
76. Mackenzie FM, Gould LM, et al. Review the post-antibiotic effect. J antimicrob. Chemother. 1993, 32:519-537.
77. Hanberger H et al. Eur J Clin InInfect Dis, 1990, 74(8):80.
78. Hanberger H et al. Eur J Clin InInfect Dis, 1991, 10(11):927.
79. Vogelman BS, et al. J antimicrob. Chemother. 1985, 15(8):37.
80．刘庆峰，大环内酯类药物的抗菌素后效应，国外医药抗生素分册，1997，3(18)：229-230。
81．刘涤洁，陈杖榴，抗菌后效应的研究进展，中国兽药杂志，1999，33(4)：53-56。
82．邱银生，抗菌后效应及其在兽医药物治疗中的意义，中国兽药杂志，2000，34(3)：51-53。
2. Yancey RJ, Brown SA, Ceftiofur Sodium: antimicrobial activity of parent ceftiofur and metabolites. Acta Veterinaria Scandinavica, 1991, 87(suppl.): 95-97.
3. Shryock T R, White DW, Wemer CS, Antimicrobial Susceptibity of Moraxella bovis. Vet Microbial, 1998, 61(4): 305-309.
4. Soback TR, G. Ziv, Winkler M, et al. Pharmacokinetics of ceftiofur administered intravenously and intramuscularly to lactating cows. Israeli journal of ret ned, 1989(4): 118-123.
5. Watts J, Salmon SA, Yancey RJ, et al. Antimicrobial Susceptibity of microorganisms islated form mammany glands of diary heifers. Diary Sci., 1995(78): 1637-1648.
6. Folz S D, Hanson, B J, Griffin AK, et al. Treatment of respiratory infections in horses with ceftiofur sodium. Equine Veterinary journal, 1992(24):300-304.
7. Raemdonck D L, Tanner A C, Tolling ST, et al. Antimicrobial Susceptibity of Actinobacillus Pleuropneumoniae, pasteurella multocida and salmonella choleraesuis isolateds from pigs Vet, Rec, 1994, 134(1):5-7.
8. Dixon BA, Issvoran GS, The activity of ceftiofur sodium for aeromons spp. Isolated form omamental fish. J Wild Dis, 1992, 28(3): 453-456.
9. Salmon SA, Watts JL, Yancey RJ, In vitro activity of ceftiofur and its primary metaolite, deuroylceftiofur, against organisms of veterinary importance. J vet Diagno Invest, 1996, 8(3): 332-336.
10. Prem S Jalan, Thomas S, Arnold, Mavc F. Kubicek, Metabolism of ceftiofur. Nature of uriny and plasma metabolism in rats and cattle. Journal of agricultural and food chemistery, 1989, 37, 1110-1112.
11. Prem, S jaglan, Fred S Yein, Res E Homish, et al. Depletion of intramuscularly injected ceftiofur from the milk of diary cattle. 1992 J Diary Science 75:1870-1876.
12. Steven L Halsead, Robert D. walker, Pharmacokinetics of Ceftiofur in serum, Tissue, chamber fluid and bronchial secretions form healthy beef-bred cattles:Can J Vet Res 1992, 56, 267-274.
13. Brown SA, Chester S T, Robb EJ, et al. Effect of age on the pharmacokinectics of single dose ceftiofur sodium administered intramhsculary or intravenously to cattle. J Vet Pharmacol Ther. 11996, 19(1):32-38.
14. Jaglan PS, Roof RD, Yein FS, et al. Concentration of ceftiofur metabolites in plasma and lungs horses following intramuscular treament J Vet. Pharmacol. Ther. 17, 24-30, 1994.
15. Marry Ann Guglick, Charles G Macallister, Cyrill R Clarke, et al. Pharmacokinetics of cefepime and comparion with those of ceftiofur in horses, AJVR, Vol59.No.4 April 1998.
16. Meyer J C, Brown MB, Grownwall RR, et al. Pharmacokinetics of ceftiofur sodium in neohatal foals after intramuscular injection. Equine Vet J. 1992, 24, 485-486.
17. Cervantes CC, Brown MB, Grownwall RR, et al.. Pharmacokinetics of ceftiofur sodium in body fluids and endometrium after repeated intramuscular in mares, Am, J, Vet Res 1993, 54: 573-575.
18. Brown SA, Hanson BJ, Mionot A, et al. Comparison of plasma pharmacokinetics and bioaviability of ceftiofur sodium and ceftiofur hydrochloride in pigs after asingle intramuscular injection J vet pharmacol. Therap. 22, 35-40.
19. Courtin F, Graigmill AL, Wetzlich SE, et al. Pharmacokinetics of ceftiofur and metabolits after single intravenous and intramuscular administration and mutiple intramuscular admintration of ceftiofur sodium to dairy goats J vet pharmacol. Therap. 1997, 20 (5):368-373.
20. Caraigmill AL, Brown SA, Wetzlich SE, et al Courtin F, Graigmill AL, et al. Pharmacokinetics of ceftiofur and metabolits after single intravenous and intramuscular administration and mutiple intramuscular admintration of ceftiofur sodium to sheeo. J vet pharmacol. Therap. 1992, 19 (6):431-438.
21. Foreman JH, Hungerferd LL, Folz SD, et al. Ceftiofur sodium for the trementment of naturally-acquired respiratory tract infections in horses, Joural of Veterinary interal medivine(1993).
22. Kesler DJ, Bechtol DJ, Efficacy of sustained release needle-less ceftiofur sodium implants in treating calves with bovine respiratory disease J zentrabl veterinarmed, 1999, 46:25-35.
23. Navarre CB, Zhang, Sunkara G, et al. Ceftiofur distribution in plasma and joint fluid following regional limb injection in cattle. J vet. Pharmacol, therap. 22,13-19.
24. Wallgren P, Segall T, Segall T, et al. Experimental infections with actinobacillus pleuropeumoniae in pigs. comparion of five different parenteral antibiotic traments. Zntrabl veterinarined, 1999, 46(4):249-260.
25. Navarre CB, Zhang, Ceftiofur distribution in plasma and joint fuid following regional limb injection in cattle. J vet. Pharmacol, therap. 22, 13-19.
26. Wallgren P, Segall T, et al. Experimental infections with actinobacillus pleuropeumoniae in pigs. comparion of five different parenteral antibiotic traments Zntrabl veterinarined, 1999, 46(4): 249-260.
27. Dvidson RJ, Zhanel GG, et al. Human serum enhances the postantibiotic effect of fluoroqunolones against staphylococcusaures. Anticrobial agents and chemotherapy 1991, 6(35): 1261-1263.
28. Ellis LS, Benson CA, Postantibiotic effect of clarithromycin alone and combined with ethambutol against mycobacterium avium complex. Antimicrobial and chemotiherapy 12(39):2803-2806.
29. Watanabe T, Kanno M, Tejima E, et al.. Effects of macrolides on ultrastructure of staphylococcus aureus during postantibiotics phase Drugs Exptl Clin Res 1992, 18(3): 81-88.
30. FuurstedD, KnudsenJD, et, al. Comparative study of bactericidal activities, posteantibicotic effects, and effects on bacterial virulence of pencillin and six marcrolids against streptococcuspneumoniae. Antimicrobialandchemotiherapy, 1997, 8(41): 1693-96.
31. Gicquel M, SandersP, Posteantibicotic effects of enrofloxacin on respiratory pathogens in pigs: pasteurella multocida, bordetella bronchiseptica and actinobacillus pleuropneumoniae. J vet pharmacol therap 1997, 20: 21-86
32. Aeschlimann JR, Dresser LD, Effect of nora inhibitors on in vitro antibacterial activities and postantibiotic effects of levofloxacin, ciproxacin, and norfloxacin in genetically related strains of staphylococcus auresus. antimicrocial agents and chemotherapy. 1999, 2(43):335-340.
33. Elisabeth Lowdin, A new method to determine post -antibiotic-effects and effects ofsub-inhibitoryantibioticconcentration. antimicrocialagentsandchemotherapy, 1993, 37(10):2200-2205.
34. Odenholt I, Holm SE, et al. Effects of benzylpencillin on streptococcus pyogenes during the post-antibiotic phase in vitro J antimicrob. Chemother.. 1989, 24: 147-156.
35．方翼，王睿，3种氟喹诺酮类药物抗菌后效应的研究，中国抗生素杂志，1997，1(22)：67-70。
36．张烨，李家泰，新氨基糖苷类抗生素89-07抗生素后效应研究，中国抗生素杂志，6(20)：429-433。
37．朱汝锦 译，斯帕沙星和环丙沙星对绿脓杆菌和粪链球菌的体外抗生素后效应，国外医药抗生素分册，1995，16(6)：450-452。
38．方翼，王睿，斯帕沙星和洛美沙星的抗生素后效应，中国新药杂志，8(9)：608-610。
39．王志强，陈杖榴，兽用氟喹诺酮类药物在猪体内外抗菌后效应初报，畜牧兽医学报，2002，33(5)：477-481
40．胡功政，李敏，左旋氧氟沙星的药效学研究，华中农业大学学报，2002，21(2)130-134。
41．刘爱芳，李昌文等，单诺沙星对大肠杆菌和金黄色葡萄球菌的体外抗菌后效应，黑龙江畜牧与兽医，2002，(2)：6-8。
42．俞树荣，微生物和微生物学检验，人民卫生出版社，1997。
43．卢中华，催保安，兽医微生物学，河南科技出版社，1996。
44．崔风珍，鹿梅花，微生物学检验，人民卫生出版社，1993。
45．杨春生，临床检验学，天津科学技术出版社，1997。
46．戴自英，临床抗菌药物学，人民卫生出版社，1985。
47．庄景新，李泰兴，速解灵与马立克疫苗混合接种对鸡免疫效果观察，畜牧与兽医，30卷，1998第四期。
48．胡功政，张许科，沙拉沙星对鸡细菌病的药效学研究，中国预防兽医学报，2000，第22卷，第1期。
49．曾振灵，刘雅红，氧氟沙星对实验性鸡大肠杆菌病的药效学研究，中国兽医学报，1996，第16卷，第5期。
50．丁焕中，陈杖榴，兽用抗生素头孢噻呋的研究进展，中兽医医药杂志，2000，第4期。
51．王付民，胡功政，新的抗菌药-头孢噻呋，信阳高等专科学校学报，2001，第1期。
52．陈杖榴等，兽医药理学，中国农业出版社，2002，第二版。
53．宋振玉，刘耕陶，当代药理学，1994，第一版。
54．杨世杰，王怀良，药理学，人民卫生出版社，2001，第一版。
55．王睿，临床治疗手册，人民军医出版社，1994，第一版。
56. Johan W. Mouton, et al. Pharmacokinetics-pharmacodynamic modeling of activity of ceftazidime during continuous and intermittent infusion. Antimicrobial agents and chemotherapy, 1996, 41(4): 733-736.
57. Walliam A Craig., Interrelationship between pharmacokinetics and pharmacodynamics in determining dosage regiments for broad spectrum cephalosporins. Dign. Microbial infect. dis 1995, 22:89-96.
58. Frederic Fitoussi, Catherine Dort, Ana sandin, et al. Killing activity of cefpirome against penicillin-resistant streptococcus pneumoniae. in a pharmacodynamic model simulating the cerebrospinal fluid concentration profile. Antimicrob. Agents chemother, 1995, 39(11): 2560-2563.
59. Gudmundsson S, et al. J Antimicrobial agents and chemotherapy, 1993, (8): 149-152.
60．胡功政，李荣誉，新全实用兽药手册，河南科学技术出版社，2002，第二版。
61．李家泰主编，临床药理学，人民卫生出版社，1998，第二版。
62. Geoge GZ, et al Ann pharmacother 1991, 2(25): 153-158
63. Blandino G et al. Drugs Exp Clin Res, 1992, 18(8): 319-324
64．王睿，刘卫，氧氟沙星与哌拉西林单用或联合应用的抗生素后效应，中国抗生素杂志，1993，18(5)：383。
65. Rodald CL, et al. Pharmacodynamic modeling of bacterial kinetics: β-lactam antibiotics against eschrichia coli J pharmaceutical sciences, 1994, 970-975.
66. Vogelman BS, et al Ann Pharmacother, 1991, 2(25): 153.
67．徐玉红，张华安，抗菌素后效应及临床意义，中国医院药学杂志 1996，16(12)：543-544。
68．方翼，β-内酰胺类抗生素后效应研究概况，国外医药抗生素分册 1998，19(3)：231-236。
69. Hanberger H et al. Antimicrob Agents Chemother, 1990, 34:102.
70. Bush L M et al. Antimicrob Agents Chemother, 1998, 32:877.
71. Fuad N et al. Biochem J 1976, 155: 623.
72．王浴生，抗生素后效应及临床意义，中国抗生素杂志，1996，21(4)：306-315。
73．陈绣枢等，体外抗菌素后效应的方法学及临床金黄色葡萄球菌的研究，1991，临床检验杂志，1991，(2)：24-25。
74．鲍燕燕，抗菌素后效应，药学情报通讯，1989，7(4)：24-25。
75．董景之，抗菌素后效应，天津药学，1997，9(3)；12-16。
76. Mackenzie FM, Gould LM, et al. Review the post-antibiotic effect. J antimicrob. Chemother. 1993, 32:519-537.
77. Hanberger H et al. Eur J Clin InInfect Dis, 1990, 74(8):80.
78. Hanberger H et al. Eur J Clin InInfect Dis, 1991, 10(11):927.
79. Vogelman BS, et al. J antimicrob. Chemother. 1985, 15(8):37.
80．刘庆峰，大环内酯类药物的抗菌素后效应，国外医药抗生素分册，1997，3(18)：229-230。
81．刘涤洁，陈杖榴，抗菌后效应的研究进展，中国兽药杂志，1999，33(4)：53-56。
82．邱银生，抗菌后效应及其在兽医药物治疗中的意义，中国兽药杂志，2000，34(3)：51-53。