大环内酯类抗生素对畜禽病原菌体外抗菌敏感性试验研究
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摘要
针对兽医临床的细菌耐药现象,为指导临床合理用药,采用微量肉汤稀释法研究了三代大环内酯类抗生素泰乐菌素、替米考星和泰地罗新对兽医临床常见的15种共74株病原菌的体外抑菌效果。结果显示:对于革兰阳性菌,泰乐菌素和替米考星对乳房炎常见的金黄色葡萄球菌、猪链球菌、无乳链球菌、停乳链球菌均有较强的抑菌活性,优于泰地罗新;泰地罗新对肺炎链球菌抑菌效果较强。对于革兰阴性菌,如支气管败血波氏杆菌、溶血性曼氏杆菌、胸膜肺炎放线杆菌、副猪嗜血杆菌等致病菌,替米考星的抑菌效果比泰乐菌素强1～64倍,泰地罗新比替米考星强2～32倍。对引起肠道感染的大肠杆菌,泰地罗新亦表现出很好的抑菌活性,效果优于泰乐菌素和替米考星。本试验为畜禽细菌性疾病的防控以及大环内酯类抗菌药物的合理使用提供了基础数据。
In view of antimicrobial resistance and regulation of the rational use of antibiotics in veterinary clinical practice,antimicrobial susceptibility test was performed on 15 species of pathogenic bacteria combined with macrolide antibacterial drugs of tylosin,tilmicosin and tildipirosin by the micro-dilution method. The results indicated that tilmicosin had similar activity to that of tylosin in Gram-positive bacteria causing mastitis such as Staphylococcus aureus, Streptococcus suis, Streptococcus agalactiae and Streptococcus dysgalactiae, whereas tildipirosin was less susceptible. For the pathogenic bacteria causing respiratory infection,i. e. Streptococcus pheumoniae,the effect of tildipirosin was better than tilmicosin and tylosin. As for the common pathogenic bacteria of Gram-negative bacteria such as Brodetella bronchiseptica,Hemolytic manella,Actinobacter pleuropium and Haemophilus parasuis,the effects of tilmicosin were 1 ～ 64 times stronger than those of tylosin,and tildipirosin were 2-32 times stronger than tilmicosin. For the pathogenic bacteria causing intestinal infections of Escherichia coli,the effects of tildipirosin were also better than those of tilmicosin and tylosin. This study provides references for prevention and therapy of bacterial disease of livestock animals and rational use of macrolide antimicrobial drugs.
In view of antimicrobial resistance and regulation of the rational use of antibiotics in veterinary clinical practice,antimicrobial susceptibility test was performed on 15 species of pathogenic bacteria combined with macrolide antibacterial drugs of tylosin,tilmicosin and tildipirosin by the micro-dilution method. The results indicated that tilmicosin had similar activity to that of tylosin in Gram-positive bacteria causing mastitis such as Staphylococcus aureus, Streptococcus suis, Streptococcus agalactiae and Streptococcus dysgalactiae, whereas tildipirosin was less susceptible. For the pathogenic bacteria causing respiratory infection,i. e. Streptococcus pheumoniae,the effect of tildipirosin was better than tilmicosin and tylosin. As for the common pathogenic bacteria of Gram-negative bacteria such as Brodetella bronchiseptica,Hemolytic manella,Actinobacter pleuropium and Haemophilus parasuis,the effects of tilmicosin were 1 ～ 64 times stronger than those of tylosin,and tildipirosin were 2-32 times stronger than tilmicosin. For the pathogenic bacteria causing intestinal infections of Escherichia coli,the effects of tildipirosin were also better than those of tilmicosin and tylosin. This study provides references for prevention and therapy of bacterial disease of livestock animals and rational use of macrolide antimicrobial drugs.
引文
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[15] Miyake T,Takita T,Hamada M,et al. Macrolide antibiotics and treatment and prophylaxis of pasteurellosis using the same:U. S.Patent 6514946 B1[P]. 2003-2-4.
[16] Andersen N M,Poehlsgaard J,Warrass R,et al. Inhibition of protein synthesis on the ribosome by tildipirosin compared with other veterinary macrolides[J]. Antimicrob Agents Chemother,2012,56(11):6033-6036.
[17] Teixeira A G V,Mcart J A A,Bicalho R C. Efficacy of tildipirosin metaphylaxis for the prevention of respiratory disease,otitis and mortality in pre-weaned holstein calves[J]. Vet J,2017,219:44-48.
[18] Ajito K,Hara O,Kurihara K,et al. 16-membered macrolide derivatives:U. S. Patent 5602106[P]. 1997-2-11.
[19] Zhao Z,Jin L,Xu Y,et al. Synthesis and antibacterial activity of a series of novel 9-O-acetyl-4'-substituted 16-membered macrolides derived from josamycin[J]. Bioorg Med Chem Lett,2014,24(2):480-484.
[20] Fu H,Marquez S,Gu X,et al. Synthesis and in vitro antibiotic activity of 16-membered 9-O-arylalkyloxime macrolides[J]. Bioorg Med Chem Lett,2006,16(5):1259-1266.
[21] EMA. CVM Passessment report Zuprevo[EB/OL].(EME/V/C/002009)http://www. ema. europa. eu/ema/index. jsp? curl=pages/medicines/veterinary/medicines/002009/vet_med_000242. jsp&murl=menus/medicines/medicines. jsp&mid=WC0b01ac058001fa1c.
[22] Menge M,Rose M,Bohland C,et al. Pharmacokinetics of tildipirosin in bovine plasma,lung tissue,and bronchial fluid(from live,nonanesthetized cattle)[J]. J Vet Pharmacol Ther,2012,35(6):550-559.
[2] Kirst H A. Semi-synthetic derivatives of 16-membered macrolide antibiotics[J]. J Med Chem,1994,31:265-295.
[3] Gray P P,Bhuwapathanapun S. Production of the macrolide antibiotic tylosin in batch and chemostat cultures[J]. Biotechnol Bioeng,2010,22(9):1785-1804.
[4] Omura S,Kitao C,Miyazawa J,et al. Bioconversion and biosynthesis of 16-membered macrolide antibiotic,tylosin,using enzyme inhibitor:cerulenin[J]. J Antibiot,1978,31(3):254-256.
[5] Dingwell R T,Leslie K E,Duffield T F,et al. Efficacy of intramammary tilmicosin and risk factors for cure of staphylococcus aureus infection in the dry period[J]. J Dairy Sci,2003,86(1):159-168.
[6] Blackall P J,Asakawa T,Graydon R J,et al. In-vitro antibacterial properties of tilmicosin against Australian isolates of pasteurella multocida and actinobacillus pleuropneumoniae from pigs[J]. Aust Vet J,2010,72(1):35-36.
[7] Menge M,Rose M,Bohland C,et al. Pharmacokinetics of tildipirosin in bovine plasma,lung tissue,and bronchial fluid(from live,nonanesthetized cattle)[J]. J Vet Pharmacol Ther,2012,35(6):550-559.
[8] Bartram D J,Moyaert H,Vanimisetti B H,et al. Comparative efficacy of tulathromycin and tildipirosin for the treatment of experimental mycoplasma bovis infection in calves[J]. Vet Med Sci,2016,2(3):170-178.
[9] Stephens D S,Zughaier S M,Whitney C G,et al. Incidence of macrolide resistance in streptococcus pneumoniae after introduction of the pneumococcal conjugate vaccine:population-based assessment[J].Lancet,2005,365(9462):855-863.
[10] Lerner U,Amram E,Ayling R D,et al. Acquired resistance to the16-membered macrolides tylosin and tilmicosin by mycoplasma bovis[J]. Vet Microbiol,2014,168(2/3/4):365-271.
[11] Watts J L,Shryock T R,Apley M,et al. Performance standards for antimicrobial disk and dilution susceptibility tests for bacteria isolated from animals,approved standard[M]. 3rd edition. Pennsylvania USA:Clinical and Laboratory Standards Institute,2008:24-33.
[12] Rose M,Menge M,Bohland C,et al. Pharmacokinetics of tildipirosin in porcine plasma,lung tissue,and bronchial fluid and effects of test conditions on in vitro activity against reference strains and field isolates of actinobacillus pleuropneumoniae[J]. J Vet Pharmacol Ther,2013,36(2):140-153.
[13] Ziv G,Shemtov M,Glickman A,et al. Tilmicosin antibacterial activity and pharmacokinetics in cows[J]. J Vet Pharmacol Ther,1995,18(5):340-345.
[14]吕淑荣,何杰,杨磊,等.兽用抗菌新药替米考星的研究[J].动物科学与动物医学,2004,21(9):7-9.
[15] Miyake T,Takita T,Hamada M,et al. Macrolide antibiotics and treatment and prophylaxis of pasteurellosis using the same:U. S.Patent 6514946 B1[P]. 2003-2-4.
[16] Andersen N M,Poehlsgaard J,Warrass R,et al. Inhibition of protein synthesis on the ribosome by tildipirosin compared with other veterinary macrolides[J]. Antimicrob Agents Chemother,2012,56(11):6033-6036.
[17] Teixeira A G V,Mcart J A A,Bicalho R C. Efficacy of tildipirosin metaphylaxis for the prevention of respiratory disease,otitis and mortality in pre-weaned holstein calves[J]. Vet J,2017,219:44-48.
[18] Ajito K,Hara O,Kurihara K,et al. 16-membered macrolide derivatives:U. S. Patent 5602106[P]. 1997-2-11.
[19] Zhao Z,Jin L,Xu Y,et al. Synthesis and antibacterial activity of a series of novel 9-O-acetyl-4'-substituted 16-membered macrolides derived from josamycin[J]. Bioorg Med Chem Lett,2014,24(2):480-484.
[20] Fu H,Marquez S,Gu X,et al. Synthesis and in vitro antibiotic activity of 16-membered 9-O-arylalkyloxime macrolides[J]. Bioorg Med Chem Lett,2006,16(5):1259-1266.
[21] EMA. CVM Passessment report Zuprevo[EB/OL].(EME/V/C/002009)http://www. ema. europa. eu/ema/index. jsp? curl=pages/medicines/veterinary/medicines/002009/vet_med_000242. jsp&murl=menus/medicines/medicines. jsp&mid=WC0b01ac058001fa1c.
[22] Menge M,Rose M,Bohland C,et al. Pharmacokinetics of tildipirosin in bovine plasma,lung tissue,and bronchial fluid(from live,nonanesthetized cattle)[J]. J Vet Pharmacol Ther,2012,35(6):550-559.