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ANTİKOAGÜLAN RODENTİSİTLERE KARŞI DİRENÇ BELİRLEME YÖNTEMLERİ

Yıl 2020, Cilt: 11 Sayı: 1, 1 - 12, 08.05.2020
https://doi.org/10.38137/vetfarmatoksbulten.704983

Öz

Antikoagülan rodentisitlerin yoğun kullanımı sonucu kemirgen popülasyonlarında 5-10 yıl içinde antikoagülanlara karşı direnç gelişebilmektedir. Antikoagülanlara karşı direnç ilk defa 1958 yılında İngiltere’de tespit edilmiştir. Kemirgen popülasyonlarında direncin belirlenmesi, entegre risk yönetiminin önemli bir unsurudur. Kemirgen mücadelesinde, uygulama doğru bir şekilde yapıldığı halde sonuç alınamaması, rodentisit direncinin bir göstergesi olarak kabul edilmektedir. Antikoagülan rodentisitlere karşı; farmakokinetik, beslenme ve farmakodinamik tabanlı üç tip direnç tanımlanmıştır. Antikoagülan rodentisit direncini belirleme yöntemleri bilimsel metotların gelişmesiyle beraber sürekli yenilenmektedir. Bu yöntemler; beslenme, kan pıhtılaşma testi (Blood Clotting Response Testing, BCRT), vitamin K epoksit redüktaz gen mutasyonun (Hepatic Vitamin K Epoxide Reductase, VKOR) belirlenmesi ve direnç belirteci genotiplerinin ortaya konulmasıdır. Popülasyonda antikoagülan rodentisitlere karşı direnç tespit edildiğinde, dirençli bireylerin belirlenmesi ve direncin yayılmasını engellemek için doğru bir strateji izlenerek mücadele edilmesi şarttır. Bu derlemede, başarılı bir kemirgen mücadelesi için antikoagülan rodentisitlere karşı gelişen direnç belirleme yöntemleri incelenmiştir.

Kaynakça

  • Baert K, Stuyck J, Breyne P, Maes D. (2012). Distribution of anticoagulant resistance in the brown rat in Belgium. Belg J Zool, 142(1):39-48.
  • Bailey CI, Eason CT. (2000). Anticoagulant resistance in rodents, Conservation Advisory Sci-ence Notes No. 297, Department of Conservation, Wellington. Citeseer.; 1-8. Erişim: https://www.doc.govt.nz/globalassets/documents/science-and-technical/casn297.pdf. Erişim tarihi:11.06.2019.
  • Bentley E. (1972). A review of anticoagulant rodenticides in current use. Bull World Health Organ, 47(3):275.
  • Berny P. Challenges of Anticoagulant Rodenticides: Resistance and Ecotoxicology. In, Marga-rita Stoytcheva Editor. Pesticide in the Modern World-Pests Control and Pesticides Exposure and Toxicity Assessment. InTech; 2011. pp 441-468.
  • Berny P, Esther A, Jacob J, Prescott C. Development of Resistance to Anticoagulant Rodentici-des in Rodents. In, Brink N,John E, Shore E. Editors. Anticoagulant Rodenticides and Wildlife. 5th ed. Oak Ridge, TN, USA. Rattner Springer, 2018. pp 259-286.
  • Bonnefoy X, Kampen H, Sweeney K. (2008). Commensal rodents. Public health significance of urban pests. Battersby S, Hirschhorn B (eds). pp 387-419. WHO Regional Office for Europe, Denmark.
  • Buckle A, Berny P. RRAC. (2015). Guidelines on anticoagulant rodenticide resistance man-agement. Ed:Rodenticide Resistance Action Committee (RRAC) of CropLife International.
  • Buckle A, Prescott C. (2012). The current status of anticoagulant resistance in rats and mice in the UK. A Report to HSE from the Rodenticide Resistance Action Group. Erişim: https://www.pestmagazine.co.uk/media/244076/rrag-anticoagulant-resistance-in-rats-and-mice-report-to-hse-may-2012.pdf. Erişim tarihi:11.06.2019.
  • Buckle AP, Eason CT. Control Methods: Chemical. In, Pelz H.J, Prescot CV. Editors. Rodent pests and their control. 2nd ed. USA, CABI, 2015. pp 123-154.
  • Buckle AP, Prescott C, Ward KJ. (1994). Resistance to the first and second generation antico-agulant rodenticides-a new perspective. Proceedings of the Sixteenth Vertebrate Pest Confer-ence. University of Nebraska – Lincoln. Erişim: http://digitalcommons.unl.edu/vpc16/7/?utm_source=digitalcommons.unl.edu%2Fvpc16%2F7&utm_medium=PDF&utm_campaign=PDFCoverPages. Erişim tarihi:11.06.2019.
  • Drummond D, Rennison BD. (1973). The detection of rodent resistance to anticoagulants. Bull World Health Organ, 48(2):239. EPPO (1995) Guideline for the evaluation of resistance to plant protection products testing ro-dents for resistance to anticoagulant rodenticides. EPPO Bulletin, 25, 575-593.
  • FARR (2013) Strategie des Fachausschusses Rodentizid Resistenz (FARR) zum Schadnager Management bei Antikoagulanzien-Resistenz. Berichte aus dem Julius. Kolloquium Rodenti-zidresistenz, Braunschweig 10. Kühn-Institut, Germany 176;4-9.
  • Gill J, MacNicoll A. (1991). Determination of the susceptibility of wild populations of the Norway rat (Rattus norvegicus) to the anticoagulant rodenticide brodifacoum. Z Angew Zool (Germany, FR).
  • Grandemange A, Lasseur R, Longin‐Sauvageon C, Benoit E, Berny P. (2010). Distribution of VKORC1 single nucleotide polymorphism in wild Rattus norvegicus in France. Pest Manag Sci, 66(3):270-276.
  • Greaves, JH. Resistance to anticoagulant rodenticides. In, Buckle AP, Smith, R. Editors. Ro-dent Pests and Their Control. Wallingford, UK. CAB International, 1994. pp 197–217.
  • Greaves J, Shepherd D, Gill J. (1982). An investigation of difenacoum resistance in Norway rat populations in Hampshire. Ann Appl Biol, 100(3):581-587.
  • Hadler M, Shadbolt R. (1975). Novel 4-hydroxycoumarin anticoagulants active against resistant rats. Nature, 253(5489):275.
  • Hodroge A, Longin-Sauvageon C, Fourel I. (2011). Biochemical characterization of spontane-ous mutants of rat VKORC1 involved in the resistance to antivitamin K anticoagulants. Arch Biochem Biophys, 515(1-2):14-20.
  • Ishizuka M, Okajima F, Tanikawa T, Min H. (2007). Elevated warfarin metabolism in warfarin-resistant roof rats (Rattus rattus) in Tokyo. Drug Metab Dispos, 35(1):62-66.
  • Lasseur R, Grandemange A, Longin‐Sauvageon C. (2006). Heterogeneity of the coumarin anti-coagulant targeted vitamin K epoxide reduction system. Study of kinetic parameters in suscepti-ble and resistant mice (Mus musculus domesticus). J Biochem Mol Toxicol, 20(5):221-229.
  • Lasseur R, Grandemange A, Longin-Sauvageon C. (2007). Comparison of the inhibition effect of different anticoagulants on vitamin K epoxide reductase activity from warfarin-susceptible and resistant rat. Pestic Biochem Physiol, 88(2):203-208.
  • Lasseur R, Longin‐Sauvageon C, Videmann B. (2006). Warfarin resistance in a French strain of rats. J Biochem Mol Toxicol, 19(6):379-385.
  • Li W, Schulman S, Dutton RJ, Boyd D, Beckwith J, Rapoport TA. (2010). Structure of a bac-terial homologue of vitamin K epoxide reductase. Nature. 463(7280):507.
  • Lund M. (1972). Rodent resistance to the anticoagulant rodenticides, with particular reference to Denmark. Bull World Health Organ, 47(5):611.
  • MacNicoll A. Resistance to 4-hydroxycoumarin anticoagulants in rodents.In, Glass E. Editor. Pesticide Resistance: Strategies and Tactics for Management. Washington DC. National Acad-emy Press, 1986. pp 87-99.
  • MacNicoll AD, Gill JE. (1993). Vitamin K3 in feedstuffs: antidotal effects in captive anticoagu-lant-resistant rats and mice. J Wild Manag, 57(4):835-841.
  • Martin A, Steed LC, Redfern R, Gill J, Huson L. (1979). Warfarin-resistance genotype deter-mination in the Norway rat, Rattus norvegicus. Lab Anim, 13(3):209-214.
  • Misenheimer TM, Lund M, Baker AEM, Suttie J. (1994). Biochemical basis of warfarin and bromadiolone resistance in the house mouse, Mus musculus domesticus. Biochem Pharmacol, 47(4):673-678.
  • Oldenburg J, Marinova M, Müller‐Reible C, Watzka M. (2008). The vitamin K cycle. Vitam Horm, 78:35-62.
  • Pelz HJ, Prescot CV. Resistance to Anticoagulant Rodenticides In, Buckle AP, Smith RH. Edi-tors. Rodent pests and their control. 2nd ed. USA. CABI, 2015. pp 187-208.
  • Pelz H, Rost S, Hünerberg M. (2005). The genetic basis of resistance to anticoagulants in ro-dents. Genetics, 170: 1839–1847.
  • Pelz HJ, Rost S, Hünerberg M, Fregin A, Heiberg A-C, Baert K, MacNicoll AD, Prescott CV, Walker A-S, Oldenburg J. (2005). The genetic basis of resistance to anticoagulants in rodents. Genetics, 170(4):1839-47.
  • Prescott CV, Buckle AP, Hussain I, Endepols S. (2007). A standardised BCR resistance test for all anticoagulant rodenticides. Int J Pest Manag, 53(4):265-272.
  • Prescott CV, Buckle AP. (2000). Blood-clotting response tests for resistance to diphacinone and chlorophacinone in the Norway Rat (Rattus norvegicus Berk.). Crop Prot, 19(5):291-296.
  • Redfern R, Gill J. (1980). Laboratory evaluation of bromadiolone as a rodenticide for use against warfarin-resistant and non-resistant rats and mice. Epidemiol Infect,84(2):263-268.
  • Rost S, Fregin A, Ivaskevicius V, Conzelmann E, Hörtnagel K, Pelz H-J, (2004). Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature, 427(6974):537.
  • Rost S, Pelz H-J, Menzel S, MacNicoll AD, León V, Oldenburg J. (2009) Novel mutations in the VKORC1 gene of wild rats and mice–a response to 50 years of selection pressure by warfa-rin? BMC Genet, 10(1):4.
  • RRAC (2003) Anticoagulant Resistance Management Strategy for Pest Management Profes-sionals, Central and Local Government and Other Competent Users of Rodenticides. Technical Monograph, Rodenticide Resistance Action Committee, CropLife International, Brussels, Bel-gium.
  • RRAG (2010) Anticoagulant Resistance in the Norway Rat and Guidelines for the Management of Resistant Rat Infestations in the UK. Rodenticide Resistance Action Group, British Pest Control Association, Derby, UK. Erişim: https://www.pestmagazine.co.uk/media/246897/management-of-resistant-norway-rat-infestations-in-the-uk-rrag-june-2010.pdf. Erişim tarihi: 11.06.2019.
  • RRAG (2012) House Mouse Resistance Guideline. Rodenticide Resistance Action Group, Brit-ish Pest Control Association, Derby, UK. Erişim: https://bpca.org.uk/write/MediaUploads/Documents/Other%20Documents/RRAG-house-mouse-resistance-guidelines-aug-2012.pdf. Erişim tarihi:11.06.2019.
  • Sugano S, Kobayashi T, Tanikawa T, Kawakami Y, Kojima H. (2001). Suppression of CYP3A2 mRNA expression in the warfarin-resistant roof rat, Rattus rattus: possible involve-ment of cytochrome P450 in the warfarin resistance mechanism. Xenobiotica, 31(7):399-407.
  • Sutcliffe FA, MacNicoll AD, Gibson GG. (1990). Hepatic microsomal warfarin metabolism in warfarin-resistant and susceptible mouse strains: influence of pretreatment with cytochrome P-450 inducers. Chem Biol Interact, 75(2):171-184.
  • Thijssen HH. (1995). Warfarin‐based rodenticides: mode of action and mechanism of re-sistance. Pestic Sci, 43(1):73-78.

METHODS OF TESTINGS FOR RESISTANCE TO ANTICOAGULANT RODENTICIDES

Yıl 2020, Cilt: 11 Sayı: 1, 1 - 12, 08.05.2020
https://doi.org/10.38137/vetfarmatoksbulten.704983

Öz

Resistance to anticoagulants may develop in rodent populations for 5-10 years as a result of intensive use of anticoagulant rodenticides. Resistance to anticoagulants have been first detected the UK in 1958. Monitoring the resistance status of rodent populations is a pivotal component of integrated risk management. Failure to get results even though the application is done correctly in rodent control is accepted as an indicator of rodenticide resistance. Failure to get results even though the application is done correctly in rodent control is accepted as an indicator of rodenticide resistance. Three types of resistance have been described against anticoagulant rodenticides based on pharmacokinetics, nutrition and pharmacodynamics. The methods of determining anticoagulant rodenticide resistance are constantly being renewed with the development of scientific methods. These methods are feeding testing, blood clotting response testing (BCRT), hepatic vitamin K epoxide reductase (VKOR) assessment, specific genotypes that are markers of resistance. When the resistance to anticoagulant rodenticides is detected in the population, it is essential to identify resistant individuals and to fight with a correct strategy to prevent the spread of resistance. In this review, resistance determination methods for anticoagulant rodenticides were investigated for a successful rodent control.

Kaynakça

  • Baert K, Stuyck J, Breyne P, Maes D. (2012). Distribution of anticoagulant resistance in the brown rat in Belgium. Belg J Zool, 142(1):39-48.
  • Bailey CI, Eason CT. (2000). Anticoagulant resistance in rodents, Conservation Advisory Sci-ence Notes No. 297, Department of Conservation, Wellington. Citeseer.; 1-8. Erişim: https://www.doc.govt.nz/globalassets/documents/science-and-technical/casn297.pdf. Erişim tarihi:11.06.2019.
  • Bentley E. (1972). A review of anticoagulant rodenticides in current use. Bull World Health Organ, 47(3):275.
  • Berny P. Challenges of Anticoagulant Rodenticides: Resistance and Ecotoxicology. In, Marga-rita Stoytcheva Editor. Pesticide in the Modern World-Pests Control and Pesticides Exposure and Toxicity Assessment. InTech; 2011. pp 441-468.
  • Berny P, Esther A, Jacob J, Prescott C. Development of Resistance to Anticoagulant Rodentici-des in Rodents. In, Brink N,John E, Shore E. Editors. Anticoagulant Rodenticides and Wildlife. 5th ed. Oak Ridge, TN, USA. Rattner Springer, 2018. pp 259-286.
  • Bonnefoy X, Kampen H, Sweeney K. (2008). Commensal rodents. Public health significance of urban pests. Battersby S, Hirschhorn B (eds). pp 387-419. WHO Regional Office for Europe, Denmark.
  • Buckle A, Berny P. RRAC. (2015). Guidelines on anticoagulant rodenticide resistance man-agement. Ed:Rodenticide Resistance Action Committee (RRAC) of CropLife International.
  • Buckle A, Prescott C. (2012). The current status of anticoagulant resistance in rats and mice in the UK. A Report to HSE from the Rodenticide Resistance Action Group. Erişim: https://www.pestmagazine.co.uk/media/244076/rrag-anticoagulant-resistance-in-rats-and-mice-report-to-hse-may-2012.pdf. Erişim tarihi:11.06.2019.
  • Buckle AP, Eason CT. Control Methods: Chemical. In, Pelz H.J, Prescot CV. Editors. Rodent pests and their control. 2nd ed. USA, CABI, 2015. pp 123-154.
  • Buckle AP, Prescott C, Ward KJ. (1994). Resistance to the first and second generation antico-agulant rodenticides-a new perspective. Proceedings of the Sixteenth Vertebrate Pest Confer-ence. University of Nebraska – Lincoln. Erişim: http://digitalcommons.unl.edu/vpc16/7/?utm_source=digitalcommons.unl.edu%2Fvpc16%2F7&utm_medium=PDF&utm_campaign=PDFCoverPages. Erişim tarihi:11.06.2019.
  • Drummond D, Rennison BD. (1973). The detection of rodent resistance to anticoagulants. Bull World Health Organ, 48(2):239. EPPO (1995) Guideline for the evaluation of resistance to plant protection products testing ro-dents for resistance to anticoagulant rodenticides. EPPO Bulletin, 25, 575-593.
  • FARR (2013) Strategie des Fachausschusses Rodentizid Resistenz (FARR) zum Schadnager Management bei Antikoagulanzien-Resistenz. Berichte aus dem Julius. Kolloquium Rodenti-zidresistenz, Braunschweig 10. Kühn-Institut, Germany 176;4-9.
  • Gill J, MacNicoll A. (1991). Determination of the susceptibility of wild populations of the Norway rat (Rattus norvegicus) to the anticoagulant rodenticide brodifacoum. Z Angew Zool (Germany, FR).
  • Grandemange A, Lasseur R, Longin‐Sauvageon C, Benoit E, Berny P. (2010). Distribution of VKORC1 single nucleotide polymorphism in wild Rattus norvegicus in France. Pest Manag Sci, 66(3):270-276.
  • Greaves, JH. Resistance to anticoagulant rodenticides. In, Buckle AP, Smith, R. Editors. Ro-dent Pests and Their Control. Wallingford, UK. CAB International, 1994. pp 197–217.
  • Greaves J, Shepherd D, Gill J. (1982). An investigation of difenacoum resistance in Norway rat populations in Hampshire. Ann Appl Biol, 100(3):581-587.
  • Hadler M, Shadbolt R. (1975). Novel 4-hydroxycoumarin anticoagulants active against resistant rats. Nature, 253(5489):275.
  • Hodroge A, Longin-Sauvageon C, Fourel I. (2011). Biochemical characterization of spontane-ous mutants of rat VKORC1 involved in the resistance to antivitamin K anticoagulants. Arch Biochem Biophys, 515(1-2):14-20.
  • Ishizuka M, Okajima F, Tanikawa T, Min H. (2007). Elevated warfarin metabolism in warfarin-resistant roof rats (Rattus rattus) in Tokyo. Drug Metab Dispos, 35(1):62-66.
  • Lasseur R, Grandemange A, Longin‐Sauvageon C. (2006). Heterogeneity of the coumarin anti-coagulant targeted vitamin K epoxide reduction system. Study of kinetic parameters in suscepti-ble and resistant mice (Mus musculus domesticus). J Biochem Mol Toxicol, 20(5):221-229.
  • Lasseur R, Grandemange A, Longin-Sauvageon C. (2007). Comparison of the inhibition effect of different anticoagulants on vitamin K epoxide reductase activity from warfarin-susceptible and resistant rat. Pestic Biochem Physiol, 88(2):203-208.
  • Lasseur R, Longin‐Sauvageon C, Videmann B. (2006). Warfarin resistance in a French strain of rats. J Biochem Mol Toxicol, 19(6):379-385.
  • Li W, Schulman S, Dutton RJ, Boyd D, Beckwith J, Rapoport TA. (2010). Structure of a bac-terial homologue of vitamin K epoxide reductase. Nature. 463(7280):507.
  • Lund M. (1972). Rodent resistance to the anticoagulant rodenticides, with particular reference to Denmark. Bull World Health Organ, 47(5):611.
  • MacNicoll A. Resistance to 4-hydroxycoumarin anticoagulants in rodents.In, Glass E. Editor. Pesticide Resistance: Strategies and Tactics for Management. Washington DC. National Acad-emy Press, 1986. pp 87-99.
  • MacNicoll AD, Gill JE. (1993). Vitamin K3 in feedstuffs: antidotal effects in captive anticoagu-lant-resistant rats and mice. J Wild Manag, 57(4):835-841.
  • Martin A, Steed LC, Redfern R, Gill J, Huson L. (1979). Warfarin-resistance genotype deter-mination in the Norway rat, Rattus norvegicus. Lab Anim, 13(3):209-214.
  • Misenheimer TM, Lund M, Baker AEM, Suttie J. (1994). Biochemical basis of warfarin and bromadiolone resistance in the house mouse, Mus musculus domesticus. Biochem Pharmacol, 47(4):673-678.
  • Oldenburg J, Marinova M, Müller‐Reible C, Watzka M. (2008). The vitamin K cycle. Vitam Horm, 78:35-62.
  • Pelz HJ, Prescot CV. Resistance to Anticoagulant Rodenticides In, Buckle AP, Smith RH. Edi-tors. Rodent pests and their control. 2nd ed. USA. CABI, 2015. pp 187-208.
  • Pelz H, Rost S, Hünerberg M. (2005). The genetic basis of resistance to anticoagulants in ro-dents. Genetics, 170: 1839–1847.
  • Pelz HJ, Rost S, Hünerberg M, Fregin A, Heiberg A-C, Baert K, MacNicoll AD, Prescott CV, Walker A-S, Oldenburg J. (2005). The genetic basis of resistance to anticoagulants in rodents. Genetics, 170(4):1839-47.
  • Prescott CV, Buckle AP, Hussain I, Endepols S. (2007). A standardised BCR resistance test for all anticoagulant rodenticides. Int J Pest Manag, 53(4):265-272.
  • Prescott CV, Buckle AP. (2000). Blood-clotting response tests for resistance to diphacinone and chlorophacinone in the Norway Rat (Rattus norvegicus Berk.). Crop Prot, 19(5):291-296.
  • Redfern R, Gill J. (1980). Laboratory evaluation of bromadiolone as a rodenticide for use against warfarin-resistant and non-resistant rats and mice. Epidemiol Infect,84(2):263-268.
  • Rost S, Fregin A, Ivaskevicius V, Conzelmann E, Hörtnagel K, Pelz H-J, (2004). Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature, 427(6974):537.
  • Rost S, Pelz H-J, Menzel S, MacNicoll AD, León V, Oldenburg J. (2009) Novel mutations in the VKORC1 gene of wild rats and mice–a response to 50 years of selection pressure by warfa-rin? BMC Genet, 10(1):4.
  • RRAC (2003) Anticoagulant Resistance Management Strategy for Pest Management Profes-sionals, Central and Local Government and Other Competent Users of Rodenticides. Technical Monograph, Rodenticide Resistance Action Committee, CropLife International, Brussels, Bel-gium.
  • RRAG (2010) Anticoagulant Resistance in the Norway Rat and Guidelines for the Management of Resistant Rat Infestations in the UK. Rodenticide Resistance Action Group, British Pest Control Association, Derby, UK. Erişim: https://www.pestmagazine.co.uk/media/246897/management-of-resistant-norway-rat-infestations-in-the-uk-rrag-june-2010.pdf. Erişim tarihi: 11.06.2019.
  • RRAG (2012) House Mouse Resistance Guideline. Rodenticide Resistance Action Group, Brit-ish Pest Control Association, Derby, UK. Erişim: https://bpca.org.uk/write/MediaUploads/Documents/Other%20Documents/RRAG-house-mouse-resistance-guidelines-aug-2012.pdf. Erişim tarihi:11.06.2019.
  • Sugano S, Kobayashi T, Tanikawa T, Kawakami Y, Kojima H. (2001). Suppression of CYP3A2 mRNA expression in the warfarin-resistant roof rat, Rattus rattus: possible involve-ment of cytochrome P450 in the warfarin resistance mechanism. Xenobiotica, 31(7):399-407.
  • Sutcliffe FA, MacNicoll AD, Gibson GG. (1990). Hepatic microsomal warfarin metabolism in warfarin-resistant and susceptible mouse strains: influence of pretreatment with cytochrome P-450 inducers. Chem Biol Interact, 75(2):171-184.
  • Thijssen HH. (1995). Warfarin‐based rodenticides: mode of action and mechanism of re-sistance. Pestic Sci, 43(1):73-78.
Toplam 43 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Veteriner Bilimleri
Bölüm Derleme
Yazarlar

Zeyno Nuhoğlu 0000-0002-1080-2926

Abdurrahman Aksoy Bu kişi benim 0000-0001-9486-312X

Yayımlanma Tarihi 8 Mayıs 2020
Kabul Tarihi 22 Nisan 2020
Yayımlandığı Sayı Yıl 2020 Cilt: 11 Sayı: 1

Kaynak Göster

APA Nuhoğlu, Z., & Aksoy, A. (2020). ANTİKOAGÜLAN RODENTİSİTLERE KARŞI DİRENÇ BELİRLEME YÖNTEMLERİ. Veteriner Farmakoloji Ve Toksikoloji Derneği Bülteni, 11(1), 1-12. https://doi.org/10.38137/vetfarmatoksbulten.704983