Effects of Ceftiofur and Chlortetracycline Treatment Strategies on Antimicrobial Susceptibility and on tet(A), tet(B), and blaCMY-2 Resistance Genes among E. coli Isolated from the Feces of Feedlot Cattle
A randomized controlled field trial was conducted to evaluate the effects of two sets of treatment strategies on ceftiofur and tetracycline resistance in feedlot cattle. The strategies consisted of ceftiofur crystalline-free acid (CCFA) administered to either one or all of the steers within a pen, followed by feeding or not feeding a therapeutic dose of chlortetracycline (CTC). Eighty-eight steers were randomly allocated to eight pens of 11 steers each. Both treatment regimens were randomly assigned to the pens in a two-way full factorial design. Non-type-specific (NTS) E. coli (n = 1,050) were isolated from fecal samples gathered on Days 0, 4, 12, and 26. Antimicrobial susceptibility profiles were determined using a microbroth dilution technique. PCR was used to detect tet(A), tet(B), and blaCMY-2 genes within each isolate. Chlortetracycline administration greatly exacerbated the already increased levels of both phenotypic and genotypic ceftiofur resistance conferred by prior CCFA treatment (P<0.05). The four treatment regimens also influenced the phenotypic multidrug resistance count of NTS E. coli populations. Chlortetracycline treatment alone was associated with an increased probability of selecting isolates that harbored tet(B) versus tet(A) (P<0.05); meanwhile, there was an inverse association between finding tet(A) versus tet(B) genes for any given regimen (P<0.05). The presence of a tet(A) gene was associated with an isolate exhibiting reduced phenotypic susceptibility to a higher median number of antimicrobials (n = 289, median = 6; 95% CI = 4–8) compared with the tet(B) gene (n = 208, median = 3; 95% CI = 3–4). Results indicate that CTC can exacerbate ceftiofur resistance following CCFA therapy and therefore should be avoided, especially when considering their use in sequence. Further studies are required to establish the animal-level effects of co-housing antimicrobial-treated and non-treated animals together.
References
[1]
Levy SB, Marshall B (2004) Antibacterial resistance worldwide: causes, challenges and responses. Nature Medicine 10: S122–129.
[2]
World Health Organisation (2001) WHO Global strategy for containment of antimicrobial resistance. Available: http://www.who.int/drugresistance/guidan？ce/en/index.html. Accessed 15 October 2013.
[3]
Van den Bogaard AE, Stobberingh EE (1999) Antibiotic usage in animals: impact on bacterial resistance and public health. Drugs 58: 589–607.
[4]
Fey PD, Safranek TJ, Rupp ME, Dunne EF, Ribot E, et al. (2000) Ceftriaxone-resistant Salmonella infection acquired by a child from cattle. New England Journal of Medicine 342: 1242–1249.
[5]
Angulo FJ, Nargund VN, Chiller TC (2004) Evidence of an association between use of anti-microbial agents in food animals and anti-microbial resistance among bacteria isolated from humans and the human health consequences of such resistance. Journal of Veterinary Medicine Series B 51: 374–379.
[6]
Lyons RW, Samples CL, DeSilva HN, Ross KA, Julian EM, et al. (1980) An epidemic of resistant Salmonella in a nursery. Animal-to-human spread. Journal of the American Medical Association 243: 546–547.
[7]
Grave K, Jensen VF, Odensvik K, Wierup M, Bangen M (2006) Usage of veterinary therapeutic antimicrobials in Denmark, Norway and Sweden following termination of antimicrobial growth promoter use. Preventive Veterinary Medicine 75: 123–132.
[8]
Wierup M (2001) The Swedish experience of the 1986 year ban of antimicrobial growth promoters, with special reference to animal health, disease prevention, productivity, and usage of antimicrobials. Microbial Drug Resistance 7: 183–190.
[9]
U. S. Food and drug Administration (2005) Withdrawal of approval of the new animal drug application for enrofloxacin in poultry. Washington D.C: U.S. Department of Health and Human Services. Available: http://www.gpo.gov/fdsys/pkg/FR-2005-08-？01/html/05-15223.htm. Accessed 15 October 2013.
[10]
National Academy of science (1999) The use of drugs in food animals; benefits and risks. Washington D.C.: National Academy Press.
[11]
Oliver SP, Murinda SE, Jayarao BM (2011) Impact of antibiotic use in adult dairy cows on antimicrobial resistance of veterinary and human pathogens: a comprehensive review. Foodborne Pathogens and Disease 8: 337–355.
[12]
Levin BR, Lipsitch M, Bonhoeffer S (1999) Population biology, evolution, and infectious disease: convergence and synthesis. Science 283: 806–809.
[13]
World Health Organization (2012) Critically important antimicrobials for human medicine (3rd revision). Available: http://www.who.int/foodborne_disease/res？istance/cia/en/. Accessed 15 October 2013.
[14]
Mann S, Siler J, Jordan D, Warnick L (2011) Antimicrobial susceptibility of fecal Escherichia coli isolates in dairy cows following systemic treatment with ceftiofur or penicillin. Foodborne Pathogens and Disease 8: 861–867.
[15]
Lamb HM, Ormrod D, Scott LJ, Figgitt DP (2002) Ceftriaxone: an update of its use in the management of community-acquired and nosocomial infections. Drugs 62: 1041–1089.
[16]
Sun Z, Jiao X, Peng Q, Jiang F, Huang Y, et al. (2013) Antibiotic resistance in Pseudomonas Aeruginosa is associated with decreased fitness. Cellular Physiology and Biochemistry 31: 347–354.
[17]
Cottell JL, Webber MA, Piddock LJ (2012) Persistence of transferable extended-spectrum-beta-lactamase resistance in the absence of antibiotic pressure. Antimicrobial Agents and Chemotherapy 56: 4703–4706.
[18]
Lipsitch M, Bergstrom CT, Levin BR (2000) The epidemiology of antibiotic resistance in hospitals: paradoxes and prescriptions. Proceedings of the National Academy of Sciences of the United States of America 97: 1938–1943.
[19]
Platt T, Loneragan G, Scott HM, Norby B, Thomson D, et al. (2008) Antimicrobial susceptibility of enteric bacteria recovered from feedlot cattle administered chlortetracycline in feed. American Journal of Veterinary Research 69: 988–996.
[20]
Lowrance TC, Loneragan GH, Kunze DJ, Platt TM, Ives SE, et al. (2007) Changes in antimicrobial susceptibility in a population of Escherichia coli isolated from feedlot cattle administered ceftiofur crystalline-free acid. American Journal of Veterinary Research 68: 501–507.
[21]
Rankin SC, Aceto H, Cassidy J, Holt J, Young S, et al. (2002) Molecular characterization of cephalosporin-resistant Salmonella enterica serotype Newport isolates from animals in Pennsylvania. Journal of Clinical Microbiology 40: 4679–4684.
[22]
Winokur PL, Brueggemann A, DeSalvo DL, Hoffmann L, Apley MD, et al. (2000) Animal and human multidrug-resistant, cephalosporin-resistant Salmonella isolates expressing a plasmid-mediated CMY-2 AmpC beta-lactamase. Antimicrobial Agents and Chemotherapy 44: 2777–2783.
[23]
Folster JP, Pecic G, Singh A, Duval B, Rickert R, et al. (2012) Characterization of extended-spectrum cephalosporin-resistant Salmonella enterica serovar Heidelberg isolated from food animals, retail meat, and humans in the United States 2009. Foodborne Pathogens and Disease 9: 638–645.
[24]
Donaldson SC, Straley BA, Hegde NV, Sawant AA, DebRoy C, et al. (2006) Molecular epidemiology of ceftiofur-resistant Escherichia coli isolates from dairy calves. Applied and Environmental Microbiology 72: 3940–3948.
[25]
Alcaine SD, Sukhnanand SS, Warnick LD, Su WL, McGann P, et al. (2005) Ceftiofur-resistant Salmonella strains isolated from dairy farms represent multiple widely distributed subtypes that evolved by independent horizontal gene transfer. Antimicrobial Agents and Chemotherapy 49: 4061–4067.
[26]
Frye JG, Fedorka-Cray PJ (2007) Prevalence, distribution and characterisation of ceftiofur resistance in Salmonella enterica isolated from animals in the USA from 1999 to 2003. International Journal of Antimicrobial Agents 30: 134–142.
[27]
Bryan A, Shapir N, Sadowsky MJ (2004) Frequency and distribution of tetracycline resistance genes in genetically diverse, nonselected, and nonclinical Escherichia coli strains isolated from diverse human and animal sources. Applied and Environmental Microbiology 70: 2503–2507.
[28]
Clinical and Laboratory Standards Institute (2011) Performance standards for antimicrobial susceptibility testing: Twenty first Informational supplement. CLSI document M100–S21. Wayne, PA.
[29]
National Antimicrobial Resistance Monitoring System (2009) National Antimicrobial Resistance Monitoring System: Animal Arm Annual Report. Georgi, Athens.
[30]
Harvey R, Funk J, Wittum TE, Hoet AE (2009) A metagenomic approach for determining prevalence of tetracycline resistance genes in the fecal flora of conventionally raised feedlot steers and feedlot steers raised without antimicrobials. American Journal of Veterinary Research 70: 198–202.
[31]
Alali WQ, Scott HM, Norby B, Gebreyes W, Loneragan GH (2009) Quantification of the bla(CMY-2) in feces from beef feedlot cattle administered three different doses of ceftiofur in a longitudinal controlled field trial. Foodborne Pathogens and Disease 6: 917–924.
[32]
Odeh R, Kelkar S, Hujer AM, Bonomo RA, Schreckenberger PC, et al. (2002) Broad resistance due to plasmid-mediated AmpC β-Lactamases in clinical isolates of Escherichia coli. Clinical Infectious Diseases 35: 140–145.
[33]
Hesketh SR, Skrondal A (2008) Multilevel and longitudinal modeling using Stata. College StationTexas: STATA. 331–372 p.
[34]
Cottell JL, Kanwar N, Castillo-Courtade L, Chalmers G, Scott HM, et al. (2013) blaCTX-M-32 on an IncN plasmid in Escherichia coli from beef cattle in the United States. Antimicrobial Agents and Chemotherapy 57: 1096–1097.
[35]
Schmidt JW, Griffin D, Kuehn LA, Brichta-Harhay DM (2013) Influence of therapeutic ceftiofur treatments of feedlot cattle on fecal and hide prevalences of commensal Escherichia coli resistant to expanded-spectrum cephalosporins, and molecular characterization of resistant isolates. Applied and Environmental Microbiology 79: 2273–2283.
[36]
Singer RS, Patterson SK, Wallace RL (2008) Effects of therapeutic ceftiofur administration to dairy cattle on Escherichia coli dynamics in the intestinal tract. Applied and Environmental Microbiology 74: 6956–6962.
[37]
Tragesser LA, Wittum TE, Funk JA, Winokur PL, Rajala-Schultz PJ (2006) Association between ceftiofur use and isolation of Escherichia coli with reduced susceptibility to ceftriaxone from fecal samples of dairy cows. American Journal of Veterinary Research 67: 1696–1700.
[38]
Norby B, Scott HM, Loneragan GH, Moore S, Kanwar N, et al.. (2011) The effect of two intervention strategies on ceftiofur resistance in E. coli., abstr O03. 4th symposium on Antimicrobial Resistance in Animal and the Environment. Tours, France. pp. 31.
[39]
Gow SP, Waldner CL, Harel J, Boerlin P (2008) Associations between antimicrobial resistance genes in fecal generic Escherichia coli isolates from cow-calf herds in western Canada. Applied and Environmental Microbiology 74: 3658–3666.
[40]
Akwar HT, Poppe C, Wilson J, Reid-Smith RJ, Dyck M, et al. (2008) Associations of antimicrobial uses with antimicrobial resistance of fecal Escherichia coli from pigs on 47 farrow-to-finish farms in Ontario and British Columbia. Canadian Journal of Veterinary Research 72: 202–210.
[41]
O' Connor AM, Poppe C, McEwen SA (2002) Changes in the prevalence of resistant Escherichia coli in cattle receiving subcutaneously injectable oxytetracycline in addition to in-feed chlortetracycline compared with cattle receiving only in-feed chlortetracycline. Canadian Journal of Veterinary Research 66: 145–150.
[42]
Boyer TC, Singer RS (2012) Quantitative measurement of bla(CMY-2) in a longitudinal observational study of dairy cattle treated with ceftiofur. Foodborne Pathogens and Disease 9: 1022–1027.
[43]
Doyle M, Loneragan GH, Scott HM, Singer RS (2013) Antimicrobial resistance: challenges and perspectives. Comprehensive Reviews in Food Science and Food Safety 12: 234–248.
[44]
Blake DP, Humphry RW, Scott KP, Hillman K, Fenlon DR, et al. (2003) Influence of tetracycline exposure on tetracycline resistance and the carriage of tetracycline resistance genes within commensal Escherichia coli populations. Journal of Applied Microbiology 94: 1087–1097.
[45]
Sengelov G, Halling-Sorensen B, Aarestrup FM (2003) Susceptibility of Escherichia coli and Enterococcus faecium isolated from pigs and broiler chickens to tetracycline degradation products and distribution of tetracycline resistance determinants in E. coli from food animals. Veterinary Microbiology 95: 91–101.
[46]
Jones CS, Osborne DJ, Stanley J (1992) Enterobacterial tetracycline resistance in relation to plasmid incompatibility. Molecular and Cellular Probes 6: 313–317.
[47]
Carattoli A, Tosini F, Giles WP, Rupp ME, Hinrichs SH, et al. (2002) Characterization of plasmids carrying CMY-2 from expanded-spectrum cephalosporin-resistant Salmonella strains isolated in the United States between 1996 and 1998. Antimicrobial Agents and Chemotherapy 46: 1269–1272.
[48]
Stegeman JA, Vernooij JCM, Khalifa OA, Van den Broek J, Mevius DJ (2006) Establishing the change in antibiotic resistance of Enterococcus faecium strains isolated from Dutch broilers by logistic regression and survival analysis. Preventive Veterinary Medicine 74: 56–66.
[49]
Hidalgo A, Carvajal A, Vester B, Pringle M, Naharro G, et al. (2011) Trends towards lower antimicrobial susceptibility and characterization of acquired resistance among clinical isolates of Brachyspira hyodysenteriae in Spain. Antimicrobial Agents and Chemotherapy 55: 3330–3337.
[50]
Hidalgo A, Carvajal A, Garcia-Feliz C, Osorio J, Rubio P (2009) Antimicrobial susceptibility testing of Spanish field isolates of Brachyspira hyodysenteriae. Research in Veterinary Science 87: 7–12.
[51]
Willett JB, Singer JD (1993) Investigating onset, cessation, relapse, and recovery: Why you should, and how you can, use discrete-time survival analysis to examine event occurrence. Journal of Consulting and Clinical Psychology 61: 952–965.
[52]
Hosmer DW, Lemeshow S (2000) Applied Logistic Regression: John Wiley & Sons Inc. 91–142 p.
[53]
Rollo SN, Norby B, Bartlett PC, Scott HM, Wilson DL, et al. (2010) Prevalence and patterns of antimicrobial resistance in Campylobacter spp isolated from pigs reared under antimicrobial-free and conventional production methods in eight states in the Midwestern United States. Journal of the American Veterinary Medical Association 236: 201–210.
[54]
Ng LK, Martin I, Alfa M, Mulvey M (2001) Multiplex PCR for the detection of tetracycline resistant genes. Molecular and Cellular Probes 15: 209–215.
