畜牧业发展中抗菌药应用的“利”与“刃”
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摘要
长期以来,抗菌药为畜牧业的健康发展一直起着保驾护航的重要作用,并且在将来较长时期内,抗菌药仍是集约化养殖业防治细菌病的主要手段。但随着抗菌药在养殖业的广泛使用,耐药菌的出现有可能使人类重新回到对多种感染无药可用的"前抗生素"黑暗时代,抗菌药的耐药性逐渐发展成为全球面临的挑战性问题。鉴于此,文章主要讨论抗菌药给畜牧业养殖所带来的正面影响,以及抗菌药使用所引发的全球耐药性问题,并针对我国国情提出关于抗菌药物应用和耐药性监管的策略、建议及面临的风险。
For decades, antimicrobials have played a key role in helping and protecting the sound development of animal husbandry. Undoubtedly, for intensive farming, antibiotics will still be one of the essential strategies for preventing and treating the bacterial infectious disease in a very long time. Nevertheless, due to the widely use of antimicrobials, the resistant bacteria and antimicrobial resistance have emerged, which become a severe challenge threatening the whole public for returning to the "pre-antibiotic era". For comprehensively understanding of this issue, here this study focuses on the pros and cons of using antibiotics in livestock, global experience in balancing the use of drugs and the control of antimicrobial resistance, and the advices and strategies are raised specifically for China.
For decades, antimicrobials have played a key role in helping and protecting the sound development of animal husbandry. Undoubtedly, for intensive farming, antibiotics will still be one of the essential strategies for preventing and treating the bacterial infectious disease in a very long time. Nevertheless, due to the widely use of antimicrobials, the resistant bacteria and antimicrobial resistance have emerged, which become a severe challenge threatening the whole public for returning to the "pre-antibiotic era". For comprehensively understanding of this issue, here this study focuses on the pros and cons of using antibiotics in livestock, global experience in balancing the use of drugs and the control of antimicrobial resistance, and the advices and strategies are raised specifically for China.
引文
1方廷松.从根上查找解决问题的答案禽畜肠道常见疾病防治国际研讨会之创新思维.中国动物保健, 2010, 12(5):10-11.
2 MoorePR,EvensonA,LuckeyTD,e ta l.U s eo f sulfasuxidine,streptothricin,andstreptomycininnutritional studies with the chick. Journal of Biological Chemistry, 1946,165(2):437-441.
3 AarestrupFM,CarstensenB.Effectoftylosinusedasa growthpromoterontheoccurrenceofmacrolide-resistant enterococciandstaphylococciinpigs.MicrobialDrug Resistance, 1998, 4(4):307-312.
4 VcS,HmM,PwC,etal.Growthresponseofswinefed penicillin. Antibiot Chemother, 1951, 1(1):41-46.
5 Jukes TH,StokstadE, TayloeR,etal.Growth-promoting effectofaureomycinonpigs. ArchivesofBiochemistryand Biophysics, 1950, 26:324-325.
6 JonesF,RickeS.Observationsonthehistoryofthe development of antimicrobials and their use in poultry feeds.Poultry Science, 2003, 82(4):613-617.
7 CastanonJ.Historyoftheuseofantibioticasgrowth promoters in European poultry feeds. Poultry Science,2007,86(11):2466-2471.
8 徐士新.我国对抗菌药物耐药性应采取的措施.中国兽药杂志, 2001, 35(6):39-41.
9 CasewellM,FriisC,MarcoE,etal. TheEuropeanbanon growth-promotingantibioticsandemergingconsequences forhumanandanimalhealth.Journalof Antimicrobial Chemotherapy, 2003, 52(2):159-161.
10 Aarestrup F M, Jensen V F, Emborg H-D, et al. Changes in the use of antimicrobials and the effects on productivity of swine farms in Denmark. American Journal of Veterinary Research,2010, 71(7):726-733.
11 Wierup M. The Swedish experience of the1986 year ban of antimicrobialgrowthpromoters,withspecialreferenceto animal health, disease prevention, productivity, and usage of antimicrobials. Microbial Drug Resistance, 2001, 7(2):183-190.
12 Wright G D. The antibiotic resistome:the nexus of chemical andgeneticdiversity.NatureReviewsMicrobiology,2007,5(3):175-186.
13 AbrahamEP,ChainE. Anenzymefrombacteriaableto destroy penicillin 1940. Reviews of Infectious Diseases, 1988,10(4):677-678.
14 DaviesJ,DaviesD.Originsandevolutionofantibiotic resistance.MicrobiologyandMolecularBiologyReviews,2010, 74(3):417-433.
15 LongKS,PoehlsgaardJ,KehrenbergC,etal.TheCfr rRNAmethyltransferaseconfersresistancetoPhenicols,Lincosamides,Oxazolidinones,Pleuromutilins,and Streptogramin Aantibiotics. Antimicrob AgentsChemother, 2006, 50(7):2500-2505.
16 Wang Y, Lv Y, Cai J, et al. A novel gene, optrA, that confers transferableresistancetooxazolidinonesandphenicolsand itspresenceinEnterococcusfaecalisandEnterococcus faecium of human and animal origin. Journal of Antimicrobial Chemotherapy, 2015, 70(8):2182-2190.
17 Canton R, Gonzalez-Alba J M, Galan J C. CTX-M Enzymes:Origin and Diffusion. Frontiers in Microbiology, 2012, 3:110.
18 Martinez-MartinezL,Pascual A,JacobyG A.Quinolone resistancefromatransferableplasmid.Lancet,1998,351(9105):797-799.
19 Walsh T R, Weeks J, Livermore D M, et al. Dissemination of NDM-1 positive bacteria in the New Delhi environment and its implications for human health:an environmental point prevalence study. The Lancet Infectious Diseases, 2011, 11(5):355-362.
20 Liu Y Y, Wang Y, Walsh TR,etal.EmergenceofplasmidmediatedcolistinresistancemechanismMCR-1inanimals and human beings in China:a microbiological and molecular biological study. The Lancet Infectious Diseases, 2016, 16(2):161-168.
21 Davies J. What are antibiotics? Archaic functions for modern activities. Molecular Microbiology, 1990, 4(8):1227-1232.
22 Dever L A, Dermody T S. Mechanisms of bacterial resistance toantibiotics. ArchivesofInternalMedicine,1991,151(5):886-895.
23 BlairJM,WebberMA,BaylayAJ,etal.Molecular mechanismsofantibioticresistance.NatureReviews Microbiology, 2015, 13(1):42.
24 Stokes H W, Gillings M R. Gene flow, mobile genetic elements and the recruitment of antibiotic resistance genes into Gramnegativepathogens.FEMSMicrobiologyReviews,2011,35(5):790-819.
25 Bennett P. Plasmid encoded antibiotic resistance:acquisition and transfer of antibiotic resistance genes in bacteria. British Journal of Pharmacology, 2008, 153(S1):S347-S357.
26 Holmes A H, Moore L S, Sundsfjord A, et al. Understanding themechanismsanddriversofantimicrobialresistance. The Lancet, 2016, 387(10014):176-187.
27 HuijbersPM,BlaakH,DeJongMC,etal.Roleofthe environmentinthetransmissionofantimicrobialresistance tohumans:areview.EnvironmentalScience&Technology,2015, 49(20):11993-12004.
28 DolejskaM,Biero?ováB,KohoutovaL,etal. AntibioticresistantSalmonellaandEscherichiacoliisolateswith integronsandextended-spectrumbeta-lactamasesinsurface waterandsympatricblack-headedgulls.Journalof Applied Microbiology, 2009, 106(6):1941-1950.
29 Van Der Bij A K, Pitout J D. The role of international travel in the worldwide spread of multiresistant Enterobacteriaceae. Journal of Antimicrobial Chemotherapy, 2012, 67(9):2090-2100.
30 MooreP,Evenson A,Luckey T,etal.Useofsulfasuxidine,streptothricin, and streptomycin in nutritional studies with the chick. Journal of Biological Chemistry, 1946, 165(2):437-441.
31 Das P, Horton R. Antibiotics:achieving the balance between access and excess. The Lancet, 2016, 387(10014):102-104.
32 LuoJ, YangQE, Yang Y Y,etal.Design,synthesis,and structure-activityrelationshipstudiesofnovelpleuromutilin derivatives having a piperazine ring. Chemical Biology Drug Design, 2016, 88:699-709.
33 MurphySK,ZengM,HerzonSB.Amodularand enantioselectivesynthesisofthepleuromutilinantibiotics.Science, 2017, 356(6341):956-959.
34 Ju L C, Cheng Z, Fast W, et al. The continuing challenge of metallo-β-lactamaseinhibition:mechanismmatters. Trends inPharmacologicalSciences, 2018.https://doi.org/10.1016/j.tips.2018.03.007.
35 Lowrence R C, Raman T, Makala H V, et al. Dithiazole thione derivative as competitive NorA efflux pump inhibitor to curtail multidrugresistantclinicalisolateofMRSAinazebrafish infectionmodel. AppliedMicrobiologyandBiotechnology,2016, 100(21):9265-9281.
36 AokiN,TatedaK,Kikuchi Y,etal.Efficacyofcolistin combination therapy in a mouse model of pneumonia caused bymultidrug-resistantPseudomonasaeruginosa.Journalof Antimicrobial Chemotherapy, 2009, 63(3):534-542.
37 GordonNC,PngK,WarehamDW.Potentsynergyand sustainedbactericidalactivityofavancomycin-colistin combination versus multidrug-resistant strains of Acinetobacter baumannii. Antimicrobial AgentsandChemotherapy,2010,54(12):5316-5322.
38 Peng B, Su Y, Li H, et al. Exogenous alanine and/or glucose pluskanamycinkillsantibiotic-resistantbacteria.Cell Metabolism, 2015, 21(2):249-262.
39 BucknerMMC,CiusaML,PiddockLJ V.Strategiesto combatantimicrobialresistance:anti-plasmidandplasmid curing. FEMS Microbiology Reviews, 2018, 42(6):781-804.
40 Z h a n gB,Te n gZ,L iX,e ta l.C h a l c o n ea t t e n u a t e s staphylococcusaureusvirulencebytargetingsortase Aand Alpha-Hemolysin. Frontiers in Microbiology, 2017, 8:1715.
41 LiH,Chen Y,ZhangB,etal.Inhibitionofsortase Aby chalconepreventsListeriamonocytogenesinfection.Biochemical Pharmacology, 2016, 106:19-29.
42 KaliaVC,PurohitHJ.Quenchingthequorumsensing system:potential antibacterial drug targets. Critical Reviews in Microbiology, 2011, 37(2):121-140.
43 RoyR, TiwariM,DonelliG,etal.Strategiesforcombating bacterialbiofilms:Afocusonanti-biofilmagentsandtheir mechanisms of action. Virulence, 2018, 9(1):522-554.
44 李伟杰,蒋桃珍,魏财文,等.我国兽用细菌疫苗生产用微生物的惠益分享现状与对策建议.中国兽药杂志, 2015,49(11):1-4.
45 GolkarZ,BagasraO,PaceDG.Bacteriophagetherapy:a potential solution for the antibiotic resistance crisis. The Journal of Infection in Developing Countries, 2014, 8(2):129-136.
46 BucknerMMC,CiusaML,PiddockLJ V.Strategiesto combatantimicrobialresistance:anti-plasmidandplasmid curing. FEMS Microbiology Reviews, 2018, 42(6):781-804.
47 U.S.FoodandDurg Administration.FDAReleases2014NARMS Integrated Report; Finds Measurable Improvements in AntimicrobialResistanceLevels.[2016-11-18].https://www.fda.gov/AnimalVeterinary/NewsEvents/CVMUpdates/ucm529719.htm.
2 MoorePR,EvensonA,LuckeyTD,e ta l.U s eo f sulfasuxidine,streptothricin,andstreptomycininnutritional studies with the chick. Journal of Biological Chemistry, 1946,165(2):437-441.
3 AarestrupFM,CarstensenB.Effectoftylosinusedasa growthpromoterontheoccurrenceofmacrolide-resistant enterococciandstaphylococciinpigs.MicrobialDrug Resistance, 1998, 4(4):307-312.
4 VcS,HmM,PwC,etal.Growthresponseofswinefed penicillin. Antibiot Chemother, 1951, 1(1):41-46.
5 Jukes TH,StokstadE, TayloeR,etal.Growth-promoting effectofaureomycinonpigs. ArchivesofBiochemistryand Biophysics, 1950, 26:324-325.
6 JonesF,RickeS.Observationsonthehistoryofthe development of antimicrobials and their use in poultry feeds.Poultry Science, 2003, 82(4):613-617.
7 CastanonJ.Historyoftheuseofantibioticasgrowth promoters in European poultry feeds. Poultry Science,2007,86(11):2466-2471.
8 徐士新.我国对抗菌药物耐药性应采取的措施.中国兽药杂志, 2001, 35(6):39-41.
9 CasewellM,FriisC,MarcoE,etal. TheEuropeanbanon growth-promotingantibioticsandemergingconsequences forhumanandanimalhealth.Journalof Antimicrobial Chemotherapy, 2003, 52(2):159-161.
10 Aarestrup F M, Jensen V F, Emborg H-D, et al. Changes in the use of antimicrobials and the effects on productivity of swine farms in Denmark. American Journal of Veterinary Research,2010, 71(7):726-733.
11 Wierup M. The Swedish experience of the1986 year ban of antimicrobialgrowthpromoters,withspecialreferenceto animal health, disease prevention, productivity, and usage of antimicrobials. Microbial Drug Resistance, 2001, 7(2):183-190.
12 Wright G D. The antibiotic resistome:the nexus of chemical andgeneticdiversity.NatureReviewsMicrobiology,2007,5(3):175-186.
13 AbrahamEP,ChainE. Anenzymefrombacteriaableto destroy penicillin 1940. Reviews of Infectious Diseases, 1988,10(4):677-678.
14 DaviesJ,DaviesD.Originsandevolutionofantibiotic resistance.MicrobiologyandMolecularBiologyReviews,2010, 74(3):417-433.
15 LongKS,PoehlsgaardJ,KehrenbergC,etal.TheCfr rRNAmethyltransferaseconfersresistancetoPhenicols,Lincosamides,Oxazolidinones,Pleuromutilins,and Streptogramin Aantibiotics. Antimicrob AgentsChemother, 2006, 50(7):2500-2505.
16 Wang Y, Lv Y, Cai J, et al. A novel gene, optrA, that confers transferableresistancetooxazolidinonesandphenicolsand itspresenceinEnterococcusfaecalisandEnterococcus faecium of human and animal origin. Journal of Antimicrobial Chemotherapy, 2015, 70(8):2182-2190.
17 Canton R, Gonzalez-Alba J M, Galan J C. CTX-M Enzymes:Origin and Diffusion. Frontiers in Microbiology, 2012, 3:110.
18 Martinez-MartinezL,Pascual A,JacobyG A.Quinolone resistancefromatransferableplasmid.Lancet,1998,351(9105):797-799.
19 Walsh T R, Weeks J, Livermore D M, et al. Dissemination of NDM-1 positive bacteria in the New Delhi environment and its implications for human health:an environmental point prevalence study. The Lancet Infectious Diseases, 2011, 11(5):355-362.
20 Liu Y Y, Wang Y, Walsh TR,etal.EmergenceofplasmidmediatedcolistinresistancemechanismMCR-1inanimals and human beings in China:a microbiological and molecular biological study. The Lancet Infectious Diseases, 2016, 16(2):161-168.
21 Davies J. What are antibiotics? Archaic functions for modern activities. Molecular Microbiology, 1990, 4(8):1227-1232.
22 Dever L A, Dermody T S. Mechanisms of bacterial resistance toantibiotics. ArchivesofInternalMedicine,1991,151(5):886-895.
23 BlairJM,WebberMA,BaylayAJ,etal.Molecular mechanismsofantibioticresistance.NatureReviews Microbiology, 2015, 13(1):42.
24 Stokes H W, Gillings M R. Gene flow, mobile genetic elements and the recruitment of antibiotic resistance genes into Gramnegativepathogens.FEMSMicrobiologyReviews,2011,35(5):790-819.
25 Bennett P. Plasmid encoded antibiotic resistance:acquisition and transfer of antibiotic resistance genes in bacteria. British Journal of Pharmacology, 2008, 153(S1):S347-S357.
26 Holmes A H, Moore L S, Sundsfjord A, et al. Understanding themechanismsanddriversofantimicrobialresistance. The Lancet, 2016, 387(10014):176-187.
27 HuijbersPM,BlaakH,DeJongMC,etal.Roleofthe environmentinthetransmissionofantimicrobialresistance tohumans:areview.EnvironmentalScience&Technology,2015, 49(20):11993-12004.
28 DolejskaM,Biero?ováB,KohoutovaL,etal. AntibioticresistantSalmonellaandEscherichiacoliisolateswith integronsandextended-spectrumbeta-lactamasesinsurface waterandsympatricblack-headedgulls.Journalof Applied Microbiology, 2009, 106(6):1941-1950.
29 Van Der Bij A K, Pitout J D. The role of international travel in the worldwide spread of multiresistant Enterobacteriaceae. Journal of Antimicrobial Chemotherapy, 2012, 67(9):2090-2100.
30 MooreP,Evenson A,Luckey T,etal.Useofsulfasuxidine,streptothricin, and streptomycin in nutritional studies with the chick. Journal of Biological Chemistry, 1946, 165(2):437-441.
31 Das P, Horton R. Antibiotics:achieving the balance between access and excess. The Lancet, 2016, 387(10014):102-104.
32 LuoJ, YangQE, Yang Y Y,etal.Design,synthesis,and structure-activityrelationshipstudiesofnovelpleuromutilin derivatives having a piperazine ring. Chemical Biology Drug Design, 2016, 88:699-709.
33 MurphySK,ZengM,HerzonSB.Amodularand enantioselectivesynthesisofthepleuromutilinantibiotics.Science, 2017, 356(6341):956-959.
34 Ju L C, Cheng Z, Fast W, et al. The continuing challenge of metallo-β-lactamaseinhibition:mechanismmatters. Trends inPharmacologicalSciences, 2018.https://doi.org/10.1016/j.tips.2018.03.007.
35 Lowrence R C, Raman T, Makala H V, et al. Dithiazole thione derivative as competitive NorA efflux pump inhibitor to curtail multidrugresistantclinicalisolateofMRSAinazebrafish infectionmodel. AppliedMicrobiologyandBiotechnology,2016, 100(21):9265-9281.
36 AokiN,TatedaK,Kikuchi Y,etal.Efficacyofcolistin combination therapy in a mouse model of pneumonia caused bymultidrug-resistantPseudomonasaeruginosa.Journalof Antimicrobial Chemotherapy, 2009, 63(3):534-542.
37 GordonNC,PngK,WarehamDW.Potentsynergyand sustainedbactericidalactivityofavancomycin-colistin combination versus multidrug-resistant strains of Acinetobacter baumannii. Antimicrobial AgentsandChemotherapy,2010,54(12):5316-5322.
38 Peng B, Su Y, Li H, et al. Exogenous alanine and/or glucose pluskanamycinkillsantibiotic-resistantbacteria.Cell Metabolism, 2015, 21(2):249-262.
39 BucknerMMC,CiusaML,PiddockLJ V.Strategiesto combatantimicrobialresistance:anti-plasmidandplasmid curing. FEMS Microbiology Reviews, 2018, 42(6):781-804.
40 Z h a n gB,Te n gZ,L iX,e ta l.C h a l c o n ea t t e n u a t e s staphylococcusaureusvirulencebytargetingsortase Aand Alpha-Hemolysin. Frontiers in Microbiology, 2017, 8:1715.
41 LiH,Chen Y,ZhangB,etal.Inhibitionofsortase Aby chalconepreventsListeriamonocytogenesinfection.Biochemical Pharmacology, 2016, 106:19-29.
42 KaliaVC,PurohitHJ.Quenchingthequorumsensing system:potential antibacterial drug targets. Critical Reviews in Microbiology, 2011, 37(2):121-140.
43 RoyR, TiwariM,DonelliG,etal.Strategiesforcombating bacterialbiofilms:Afocusonanti-biofilmagentsandtheir mechanisms of action. Virulence, 2018, 9(1):522-554.
44 李伟杰,蒋桃珍,魏财文,等.我国兽用细菌疫苗生产用微生物的惠益分享现状与对策建议.中国兽药杂志, 2015,49(11):1-4.
45 GolkarZ,BagasraO,PaceDG.Bacteriophagetherapy:a potential solution for the antibiotic resistance crisis. The Journal of Infection in Developing Countries, 2014, 8(2):129-136.
46 BucknerMMC,CiusaML,PiddockLJ V.Strategiesto combatantimicrobialresistance:anti-plasmidandplasmid curing. FEMS Microbiology Reviews, 2018, 42(6):781-804.
47 U.S.FoodandDurg Administration.FDAReleases2014NARMS Integrated Report; Finds Measurable Improvements in AntimicrobialResistanceLevels.[2016-11-18].https://www.fda.gov/AnimalVeterinary/NewsEvents/CVMUpdates/ucm529719.htm.