Review of antimicrobial resistance in the environment and its relevance to environmental regulators

Frontiers in Microbiology

Volumn 7, Issue NOV, 2016, Pages

  Singer, Andrew C ^a   Shaw, Helen ^b   Rhodes, Vicki ^c   Hart, Alwyn ^c  

^a CENTRE FOR ECOLOGY AND HYDROLOGY   (United Kingdom)

^b Food and Rural Affairs   (United Kingdom)

^c ENVIRONMENT AGENCY   (United Kingdom)

Author keywords

AMR; Antibiotics; Antimicrobial resistance; Biocide; Genes; Metals; Plasmid

Indexed keywords

ANTIBIOTIC AGENT; AZITHROMYCIN; BIOCIDE; CIPROFLOXACIN; DOXYCYCLINE; EPITETRACYCLINE; ERYTHROMYCIN; GROUND WATER; HEAVY METAL; MINOCYCLINE; OFLOXACIN; OXYTETRACYCLINE; SULFONAMIDE; TETRACYCLINE; TRICLOCARBAN; TRICLOSAN;

AEROSOL; ANIMAL HUSBANDRY; ANTIBIOTIC RESISTANCE; AQUACULTURE; BIODEGRADATION; BIOSOLID; DRUG CONCENTRATION; ECOSYSTEM HEALTH; ENVIRONMENTAL PROTECTION; FOOD CROP; GENOTYPE ENVIRONMENT INTERACTION; HUMAN; LIVESTOCK; MANURE; MINIMUM INHIBITORY CONCENTRATION; NONHUMAN; REVIEW; SLUDGE TREATMENT; WASTE WATER MANAGEMENT; WASTE WATER TREATMENT PLANT; WATER QUALITY; WORLD HEALTH ORGANIZATION;

EID: 85006751480     PISSN: None     EISSN: 1664302X     Source Type: Journal    
DOI: 10.3389/fmicb.2016.01728     Document Type: Review

References (250)

1. Aga, D. S., Lenczewski, M., Snow, D., Muurinen, J., Sallach, J. B., and Wallace, J. S. (2016). Challenges in the measurement of antibiotics and in evaluating their impacts in agroecosystems: a critical review. J. Environ. Qual. 45, 407-419. doi: 10.2134/jeq2015.07.0393.
2. Ahmad, M., Vithanage, M., Kim, K., Cho, J.-S., Lee, Y. H., Joo, Y. K., et al. (2014). Inhibitory effect of veterinary antibiotics on denitrification in groundwater: a microcosm approach. Sci. World J. 2014, 879831. doi: 10.1155/2014/879831.
3. Ahmed, M. B., Zhou, J. L., Ngo, H. H., and Guo, W. (2015). Adsorptive removal of antibiotics from water and wastewater: progress and challenges. Sci. Total Environ. 532, 112-126. doi: 10.1016/j.scitotenv.2015.05.130.
4. Ajmal, M., Ahmad, A., and Nomani, A. A. (1983). Influence of toxic metals on the repression of carbonaceous oxygen demand. Water Res. 17, 799-802. doi: 10.1016/0043-1354(83)90074-X.
5. Alekshun, M. N., and Levy, S. B. (1999). The mar regulon: multiple resistance to antibiotics and other toxic chemicals. Trends Microbiol. 7, 410-413. doi: 10.1016/S0966-842X(99)01589-9.
6. Allison, S., and Martiny, J. (2008). Resistance, resilience, and redundancy in microbial communities. Proc. Natl. Acad. Sci. U.S.A. 105(Suppl. 1), 11512-11519. doi: 10.1073/pnas.0801925105.
7. Amini, S., Hottes, A. K., Smith, L. E., and Tavazoie, S. (2011). Fitness landscape of antibiotic tolerance in Pseudomonas aeruginosa biofilms. PLoS Pathog. 7:e1002298. doi: 10.1371/journal.ppat.1002298.
8. Aminov, R. I. (2010). A brief history of the antibiotic era: lessons learned and challenges for the future. Front. Microbiol. 1:134. doi: 10.3389/fmicb.2010.00134.
9. Antonova, E. S., and Hammer, B. K. (2011). Quorum-sensing autoinducer molecules produced by members of a multispecies biofilm promote horizontal gene transfer to Vibrio cholerae. FEMS Microbiol. Lett. 322, 68-76. doi: 10.1111/j.1574-6968.2011.02328.x.
10. Ardestani, M. M., van Straalen, N. M., and van Gestel, C. A. M. (2015). Biotic ligand modeling approach: synthesis of the effect of major cations on the toxicity of metals to soil and aquatic organisms. Environ. Toxicol. Chem. 34, 2194-2204. doi: 10.1002/etc.3060.
11. Aust, M.-O., Godlinski, F., Travis, G. R., Hao, X., McAllister, T. A., Leinweber, P., et al. (2008). Distribution of sulfamethazine, chlortetracycline and tylosin in manure and soil of Canadian feedlots after subtherapeutic use in cattle. Environ. Pollut. 156, 1243-1251. doi: 10.1016/j.envpol.2008.03.011.
12. Azanu, D., Mortey, C., Darko, G., Weisser, J. J., Styrishave, B., and Abaidoo, R. C. (2016). Uptake of antibiotics from irrigation water by plants. Chemosphere 157, 107-114. doi: 10.1016/j.chemosphere.2016.05.035.
13. Baguer, A. J., Jensen, J., and Krogh, P. H. (2000). Effects of the antibiotics oxytetracycline and tylosin on soil fauna. Chemosphere 40, 751-757. doi: 10.1016/S0045-6535(99)00449-X.
14. Baharoglu, Z., and Mazel, D. (2014). SOS, the formidable strategy of bacteria against aggressions. FEMS Microbiol. Rev. 38, 1126-1145. doi: 10.1111/1574-6976.12077.
15. Baker-Austin, C., Wright, M. S., Stepanauskas, R., and McArthur, J. V. (2006). Co-selection of antibiotic and metal resistance. Trends Microbiol. 14, 176-182. doi: 10.1016/j.tim.2006.02.006.
16. Baquero, F., and Negri, M. C. (1997). Selective compartments for resistant microorganisms in antibiotic gradients. Bioessays 19, 731-736. doi: 10.1002/bies.950190814.
17. Bardgett, R. D., and van der Putten, W. H. (2014). Belowground biodiversity and ecosystem functioning. Nature 515, 505-511. doi: 10.1038/nature13855.
18. Bartelt-Hunt, S., Snow, D. D., Damon-Powell, T., and Miesbach, D. (2011). Occurrence of steroid hormones and antibiotics in shallow groundwater impacted by livestock waste control facilities. J. Contam. Hydrol. 123, 94-103. doi: 10.1016/j.jconhyd.2010.12.010.
19. Beaber, J. W., Hochhut, B., and Waldor, M. K. (2004). SOS response promotes horizontal dissemination of antibiotic resistance genes. Nature 427, 72-74. doi: 10.1038/nature02241.
20. Berendsen, B. J. A., Wegh, R. S., Memelink, J., Zuidema, T., and Stolker, L. A. M. (2015). The analysis of animal faeces as a tool to monitor antibiotic usage. Talanta 132, 258-268. doi: 10.1016/j.talanta.2014.09.022.
21. Blanco, P., Hernando-Amado, S., Reales-Calderon, J., Corona, F., Lira, F., Alcalde-Rico, M., et al. (2016). Bacterial multidrug e?ux pumps: much more than antibiotic resistance determinants. Microorganisms 4:E14. doi: 10.3390/microorganisms4010014.
22. Bondarczuk, K., Markowicz, A., and Piotrowska-Seget, Z. (2016). The urgent need for risk assessment on the antibiotic resistance spread via sewage sludge land application. Environ. Int. 87, 49-55. doi: 10.1016/j.envint.2015.11.011.
23. Boxall, A. B. A., Johnson, P., Smith, E. J., Sinclair, C. J., Stutt, E., and Levy, L. S. (2006). Uptake of veterinary medicines from soils into plants. J. Agric. Food Chem. 54, 2288-2297. doi: 10.1021/jf053041t.
24. Braam, F., and Klapwijk, A. (1981). Effect of copper on nitrification in activated sludge. Water Res. 15, 1093-1098. doi: 10.1016/0043-1354(81)90077-4.
25. Bragginton, E. C., and Piddock, L. J. V. (2014). UK and European Union public and charitable funding from 2008 to 2013 for bacteriology and antibiotic research in the UK: an observational study. Lancet Infect. Dis. 14, 857-868. doi: 10.1016/S1473-3099(14)70825-4.
26. Bridier, A., Briandet, R., Thomas, V., and Dubois-Brissonnet, F. (2011). Resistance of bacterial biofilms to disinfectants: a review. Biofouling 27, 1017-1032. doi: 10.1080/08927014.2011.626899.
27. Brown-Jaque, M., Calero-Cáceres, W., and Muniesa, M. (2015). Transfer of antibiotic-resistance genes via phage-related mobile elements. Plasmid 79, 1-7. doi: 10.1016/j.plasmid.2015.01.001.
28. BSI (2014). PAS 110: Specification for Whole Digestate, Separated Liquor and Separated Fibre Derived from the Anaerobic Digestion of Source-Segregated Biodegradable Materials. London: British standards institution.
29. Buffet-Bataillon, S., Tattevin, P., Bonnaure-Mallet, M., and Jolivet-Gougeon, A. (2012). Emergence of resistance to antibacterial agents: the role of quaternary ammonium compounds-a critical review. Int. J. Antimicrob. Agents 39, 381-389. doi: 10.1016/j.ijantimicag.2012.01.011.
30. Buffet-Bataillon, S., Tattevin, P., Maillard, J.-Y., Bonnaure-Mallet, M., and Jolivet-Gougeon, A. (2016). E?ux pump induction by quaternary ammonium compounds and fluoroquinolone resistance in bacteria. Future Microbiol. 11, 81-92. doi: 10.2217/fmb.15.131.
31. Burridge, L., Weis, J. S., Cabello, F., Pizarro, J., and Bostick, K. (2010). Chemical use in salmon aquaculture: a review of current practices and possible environmental effects. Aquaculture 306, 7-23. doi: 10.1016/j.aquaculture.2010.05.020.
32. Byrne-Bailey, K. G., Gaze, W. H., Zhang, L., Kay, P., Boxall, A., Hawkey, P. M., et al. (2011). Integron prevalence and diversity in manured soil. Appl. Environ. Microbiol. 77, 684-687. doi: 10.1128/AEM.01425-10.
33. Cabello, F. C. (2006). Heavy use of prophylactic antibiotics in aquaculture: a growing problem for human and animal health and for the environment. Environ. Microbiol. 8, 1137-1144. doi: 10.1111/j.1462-2920.2006.01054.x.
34. Cabello, F. C., Godfrey, H. P., Tomova, A., Ivanova, L., Dölz, H., Millanao, A., et al. (2013). Antimicrobial use in aquaculture re-examined: its relevance to antimicrobial resistance and to animal and human health. Environ. Microbiol. 15, 1917-1942. doi: 10.1111/1462-2920.12134.
35. Calderón-Preciado, D., Matamoros, V., Savé, R., Muñoz, P., Biel, C., and Bayona, J. M. (2013). Uptake of microcontaminants by crops irrigated with reclaimed water and groundwater under real field greenhouse conditions. Environ. Sci. Pollut. Res. Int. 20, 3629-3638. doi: 10.1007/s11356-013-1509-0.
36. Calero-Cáceres, W., Melgarejo, A., Colomer-Lluch, M., Stoll, C., Lucena, F., Jofre, J., et al. (2014). Sludge as a potential important source of antibiotic resistance genes in both the bacterial and bacteriophage fractions. Environ. Sci. Technol. 48, 7602-7611. doi: 10.1021/es501851s.
37. Calero-Cáceres, W., and Muniesa, M. (2016). Persistence of naturally occurring antibiotic resistance genes in the bacteria and bacteriophage fractions of wastewater. Water Res. 95, 11-18. doi: 10.1016/j.watres.2016.03.006.
38. Call, D. R., Matthews, L., Subbiah, M., and Liu, J. (2013). Do antibiotic residues in soils play a role in amplification and transmission of antibiotic resistant bacteria in cattle populations? Front. Microbiol. 4:193. doi: 10.3389/fmicb.2013.00193.
39. Carey, C. (2000). Infectious disease and worldwide declines of amphibian populations, with comments on emerging diseases in coral reef organisms and in humans. Environ. Health Perspect. 108(Suppl. 1), 143-150. doi: 10.2307/3454639.
40. Carey, D. E., and McNamara, P. J. (2014). The impact of triclosan on the spread of antibiotic resistance in the environment. Front. Microbiol. 5:780. doi: 10.3389/fmicb.2014.00780.
41. Chait, R., Palmer, A. C., Yelin, I., and Kishony, R. (2016). Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments. Nat. Commun. 7:10333. doi: 10.1038/ncomms10333.
42. Chang, H.-H., Cohen, T., Grad, Y. H., Hanage, W. P., O'Brien, T. F., and Lipsitch, M. (2015). Origin and proliferation of multiple-drug resistance in bacterial pathogens. Microbiol. Mol. Biol. Rev. 79, 101-116. doi: 10.1128/MMBR.00039-14.
43. Chaudri, A., Mcgrath, S., Giller, K., Rietz, E., and Sauerbeck, D. (1993). Enumeration of indigenous Rhizobium leguminosarum biovar Trifolii in soils previously treated with metal-contaminated sewage sludge. Soil Biol. Biochem. 25, 301-309. doi: 10.1016/0038-0717(93)90128-X.
44. Chen, C.-E., Zhang, H., Ying, G.-G., Zhou, L.-J., and Jones, K. C. (2015). Passive sampling: a cost-effective method for understanding antibiotic fate, behaviour and impact. Environ. Int. 85, 284-291. doi: 10.1016/j.envint.2015.10.001.
45. Chen, Y., Yu, G., Cao, Q., Zhang, H., Lin, Q., and Hong, Y. (2013). Occurrence and environmental implications of pharmaceuticals in Chinese municipal sewage sludge. Chemosphere 93, 1765-1772. doi: 10.1016/j.chemosphere.2013.06.007.
46. Chick-fil-A, Inc. (2014). Inside Chick-fil-A-Chick-fil-A to Serve Antibiotic-Free Chicken. Available at: http://inside.chick-fil-a.com/antibiotic-free-chicken/.
47. Chipasa, K. B. (2003). Accumulation and fate of selected heavy metals in a biological wastewater treatment system. Waste Manag. 23, 135-143. doi: 10.1016/S0956-053X(02)00065-X.
48. Clarke, B. O., and Smith, S. R. (2011). Review of "emerging" organic contaminants in biosolids and assessment of international research priorities for the agricultural use of biosolids. Environ. Int. 37, 226-247. doi: 10.1016/j.envint.2010.06.004.
49. Comber, S., Gardner, M., Jones, V., and Ellor, B. (2015). Source apportionment of trace contaminants in urban sewer catchments. Environ. Technol. 36, 573-587. doi: 10.1080/09593330.2014.953599.
50. Cox, G., and Wright, G. D. (2013). Intrinsic antibiotic resistance: mechanisms, origins, challenges and solutions. Int. J. Med. Microbiol. 303, 287-292. doi: 10.1016/j.ijmm.2013.02.009.
51. Crombé, F., Argudín, M. A., Vanderhaeghen, W., Hermans, K., Haesebrouck, F., and Butaye, P. (2013). Transmission dynamics of methicillin-resistant Staphylococcus aureus in Pigs. Front. Microbiol. 4:57. doi: 10.3389/fmicb.2013.00057.
52. Curiao, T., Marchi, E., Grandgirard, D., León-Sampedro, R., Viti, C., Leib, S. L., et al. (2016). Multiple adaptive routes of Salmonella enterica Typhimurium to biocide and antibiotic exposure. BMC Genomics 17:491. doi: 10.1186/s12864-016-2778-z.
53. Dantas, G., and Sommer, M. O. A. (2012). Context matters-the complex interplay between resistome genotypes and resistance phenotypes. Curr. Opin. Microbiol. 15, 577-582. doi: 10.1016/j.mib.2012.07.004.
54. Davison, J. (1999). Genetic exchange between bacteria in the environment. Plasmid 42, 73-91. doi: 10.1006/plas.1999.1421.
55. D'Costa, V. M., King, C. E., Kalan, L., Morar, M., Sung, W. W. L., Schwarz, C., et al. (2011). Antibiotic resistance is ancient. Nature 477, 457-461. doi: 10.1038/nature10388.
56. Defra (2006). Code of Practice for Agriculture Use of Sewage Sludge. Available at: http://adlib.everysite.co.uk/adlib/defra/content.aspx?id=4197.
57. Defra (2013). Core Guidance for the Environmental Permitting (England and Wales) Regulations 2010 (Revised 2013). Available at: http://www.legislation.gov.uk/uksi/2010/675/pdfs/uksi_20100675_en.pdf.
58. DePaola, A., Flynn, P. A., McPhearson, R. M., and Levy, S. B. (1988). Phenotypic and genotypic characterization of tetracycline-and oxytetracycline-resistant Aeromonas hydrophila from cultured channel catfish (Ictalurus punctatus) and their environments. Appl. Environ. Microbiol. 54, 1861-1863.
59. Department of Health/Defra (2013). UK Five Year Antimicrobial Resistance Strategy 2013 to 2018. Department of Health. Available at: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/244058/20130902_UK_5_year_AMR_strategy.pdf.
60. Di Cesare, A., Eckert, E. M., D'Urso, S., Bertoni, R., Gillan, D. C., Wattiez, R., et al. (2016). Co-occurrence of integrase 1, antibiotic and heavy metal resistance genes in municipal wastewater treatment plants. Water Res. 94, 208-214. doi: 10.1016/j.watres.2016.02.049.
61. Dodgen, L. K., and Zheng, W. (2016). Effects of reclaimed water matrix on fate of pharmaceuticals and personal care products in soil. Chemosphere 156, 286-293. doi: 10.1016/j.chemosphere.2016.04.109.
62. Dolliver, H., Kumar, K., and Gupta, S. (2007). Sulfamethazine uptake by plants from manure-amended soil. J. Environ. Qual. 36, 1224-1230. doi: 10.2134/jeq2006.0266.
63. Du, B., Haddad, S. P., Luek, A., Scott, W. C., Saari, G. N., Burket, S. R., et al. (2016). Bioaccumulation of human pharmaceuticals in fish across habitats of a tidally influenced urban bayou. Environ. Toxicol. Chem. 35, 966-974. doi: 10.1002/etc.3221.
64. Dwyer, D. J., Belenky, P. A., Yang, J. H., MacDonald, I. C., Martell, J. D., Takahashi, N., et al. (2014). Antibiotics induce redox-related physiological alterations as part of their lethality. Proc. Natl. Acad. Sci. U.S.A. 111, E2100-E2109. doi: 10.1073/pnas.1401876111.
65. Enault, F., Briet, A., Bouteille, L., Roux, S., Sullivan, M. B., and Petit, M.-A. (2016). Phages rarely encode antibiotic resistance genes: a cautionary tale for virome analyses. ISME J. doi: 10.1038/ismej.2016.90 [Epub ahead of print].
66. European Commission (2000). Directive 2000/60/EC of the european parliament and of the council of 23 october 2000 establishing a framework for community action in the field of water policy. Off. J. Eur. Commun. 327, 1-72.
67. European Commission (2009). Scientific Committee on Emerging and Newly Identified Health Risks. Assessment of the Antibiotic Resistance Effects of Biocides. Available at: http://ec.europa.eu/health/ph_risk/committees/04_scenihr/docs/scenihr_o_021.pdf.
68. European Commission (2011). Communication from the Commission to the European Parliament and the Council: Action Plan Against the Rising Threats from Antimicrobial Resistance. Available at: http://ec.europa.eu/dgs/health_food-safety/docs/communication_amr_2011_748_en.pdf.
69. European Commission (2012). Regulation (EU) No 528/2012 of the european parliament and of the council of 22 may 2012 concerning the making available on the market and use of biocidal products. Off. J. Eur. Union. 167, 1-123.
70. European Commission, and Health and Consumer Protection Directorate-General (2003). Opinion of the Scientific Committee for Animal Nutrition on the Use of Copper in Feeding Stuffs. Available at: http://ec.europa.eu/food/fs/sc/scan/out115_en.pdf.
71. European Medicines Agency (2015). Sales of Veterinary Antimicrobial Agents in 26 EU/EEA Countries in 2013 (EMA/387934/2015). Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Report/2015/10/WC500195687.pdf.
72. Fahrenfeld, N., Ma, Y., O'Brien, M., and Pruden, A. (2013). Reclaimed water as a reservoir of antibiotic resistance genes: distribution system and irrigation implications. Front. Microbiol. 4:130. doi: 10.3389/fmicb.2013.00130.
73. Fernandes, P. (2003). Solvent tolerance in bacteria: role of e?ux pumps and cross-resistance with antibiotics. Int. J. Antimicrob. Agents 22, 211-216. doi: 10.1016/S0924-8579(03)00209-7.
74. Ferro, G., Polo-López, M. I., Martínez-Piernas, A. B., Fernández-Ibáñez, P., Agüera, A., and Rizzo, L. (2015). Cross-contamination of residual emerging contaminants and antibiotic resistant bacteria in lettuce crops and soil irrigated with wastewater treated by Sunlight/H2O2. Environ. Sci. Technol. 49, 11096-11104. doi: 10.1021/acs.est.5b02613.
75. Fick, J., Lindberg, R. H., Tysklind, M., and Larsson, D. G. J. (2010). Predicted critical environmental concentrations for 500 pharmaceuticals. Regul. Toxicol. Pharmacol. 58, 516-523. doi: 10.1016/j.yrtph.2010.08.025.
76. Finley, S., Barrington, S., and Lyew, D. (2009). Reuse of domestic greywater for the irrigation of food crops. Water Air Soil Pollut. 199, 235-245. doi: 10.1007/s11270-008-9874-x.
77. Forsberg, K. J., Reyes, A., Wang, B., Selleck, E. M., Sommer, M. O. A., and Dantas, G. (2012). The shared antibiotic resistome of soil bacteria and human pathogens. Science 337, 1107-1111. doi: 10.1126/science.1220761.
78. Fortuna, A.-M., Honeycutt, C. W., Vandemark, G., Griffin, T. S., Larkin, R. P., He, Z., et al. (2012). Links among nitrification, nitrifier communities, and edaphic properties in contrasting soils receiving dairy slurry. J. Environ. Qual. 41, 262-272. doi: 10.2134/jeq2011.0202.
79. Foster, K. R., and Grundmann, H. (2006). Do we need to put society first? The potential for tragedy in antimicrobial resistance. PLoS Med. 3:e29. doi: 10.1371/journal.pmed.0030029.
80. Fournié, G. J., Mas, M., Cautain, B., Savignac, M., Subra, J. F., Pelletier, L., et al. (2001). Induction of autoimmunity through bystander effects. Lessons from immunological disorders induced by heavy metals. J. Autoimmun. 16, 319-326. doi: 10.1006/jaut.2000.0482.
81. Friedman, M. (2015). Antibiotic-resistant bacteria: prevalence in food and inactivation by food-compatible compounds and plant extracts. J. Agric. Food Chem. 63, 3805-3822. doi: 10.1021/acs.jafc.5b00778.
82. Frost, L. S., Leplae, R., Summers, A. O., and Toussaint, A. (2005). Mobile genetic elements: the agents of open source evolution. Nat. Rev. Microbiol. 3, 722-732. doi: 10.1038/nrmicro1235.
83. Fu, F., and Wang, Q. (2011). Removal of heavy metal ions from wastewaters: a review. J. Environ. Manage. 92, 407-418. doi: 10.1016/j.jenvman.2010.11.011.
84. García-Galán, M. J., Garrido, T., Fraile, J., Ginebreda, A., Díaz-Cruz, M. S., and Barceló, D. (2010). Simultaneous occurrence of nitrates and sulfonamide antibiotics in two ground water bodies of Catalonia (Spain). J. Hydrol. (Amst.) 383, 93-101. doi: 10.1016/j.jhydrol.2009.06.042.
85. Gardner, M., Jones, V., Comber, S., Scrimshaw, M. D., Coello-Garcia, T., Cartmell, E., et al. (2013). Performance of UK wastewater treatment works with respect to trace contaminants. Sci. Total Environ. 45, 359-369. doi: 10.1016/j.scitotenv.2013.03.088.
86. Gaze, W. H., Abdouslam, N., Hawkey, P. M., and Wellington, E. M. H. (2005). Incidence of class 1 integrons in a quaternary ammonium compound-polluted environment. Antimicrob. Agents Chemother. 49, 1802-1807. doi: 10.1128/AAC.49.5.1802-1807.2005.
87. Gaze, W. H., Krone, S. M., Larsson, D. G. J., Li, X.-Z., Robinson, J. A., Simonet, P., et al. (2013). Influence of humans on evolution and mobilization of environmental antibiotic resistome. Emerg. Infect. Dis. 19. doi: 10.3201/eid1907.120871.
88. Gelband, H., Miller-Petrie, M., Pant, S., Gandra, S., Levinson, J., Barter, D., et al. (2015). The State of the World's Antibiotics. Washington, DC: Centre for Disease Dynamics, Economics & Policy.
89. Gifford, D. R., Moss, E., and MacLean, R. C. (2016). Environmental variation alters the fitness effects of rifampicin resistance mutations in Pseudomonas aeruginosa. Evolution 70, 725-730. doi: 10.1111/evo.12880.
90. Giller, K. E., Witter, E., and Mcgrath, S. P. (1998). Toxicity of heavy metals to microorganisms and microbial processes in agricultural soils: a review. Soil Biol. Biochem. 30, 1389-1414. doi: 10.1016/S0038-0717(97)00270-8.
91. Goossens, H., Ferech, M., Vander Stichele, R., Elseviers, M., and Esac Project Group. (2005). Outpatient antibiotic use in Europe and association with resistance: a cross-national database study. Lancet 365, 579-587. doi: 10.1016/S0140-6736(05)17907-0.
92. Graham, D. W., Knapp, C. W., Christensen, B. T., McCluskey, S., and Dolfing, J. (2016). Appearance of β-lactam resistance genes in agricultural soils and clinical isolates over the 20(th) century. Sci. Rep. 6:21550. doi: 10.1038/srep21550.
93. Gros, M., Rodríguez-Mozaz, S., and Barceló, D. (2013). Rapid analysis of multiclass antibiotic residues and some of their metabolites in hospital, urban wastewater and river water by ultra-high-performance liquid chromatography coupled to quadrupole-linear ion trap tandem mass spectrometry. J. Chromatogr. A 1292, 173-188. doi: 10.1016/j.chroma.2012.12.072.
94. Guardabassi, L., Dalsgaard, A., Raffatellu, M., and Olsen, J. E. (2000). Increase in the prevalence of oxolinic acid resistant Acinetobacter spp. observed in a stream receiving the e?uent from a freshwater trout farm following the treatment with oxolinic acid-medicated feed. Aquaculture 188, 205-218. doi: 10.1016/S0044-8486(00)00340-9.
95. Gullberg, E., Albrecht, L. M., Karlsson, C., Sandegren, L., and Andersson, D. I. (2014). Selection of a multidrug resistance plasmid by sublethal levels of antibiotics and heavy metals. MBio 5:e01918-14. doi: 10.1128/mBio.01918-14.
96. Gullberg, E., Cao, S., Berg, O. G., Ilbäck, C., Sandegren, L., Hughes, D., et al. (2011). Selection of resistant bacteria at very low antibiotic concentrations. PLoS Pathog. 7:e1002158. doi: 10.1371/journal.ppat.1002158.
97. Halling-Sørensen, B. (2001). Inhibition of aerobic growth and nitrification of bacteria in sewage sludge by antibacterial agents. Arch. Environ. Contam. Toxicol. 40, 451-460. doi: 10.1007/s002440010197.
98. Hamilton, A. J., Boland, A.-M., Stevens, D., Kelly, J., Radcliffe, J., Ziehrl, A., et al. (2005). Position of the Australian horticultural industry with respect to the use of reclaimed water. Agric. Water Manage. 71, 181-209. doi: 10.1016/j.agwat.2004.11.001.
99. Hammer, T. J., Fierer, N., Hardwick, B., Simojoki, A., Slade, E., Taponen, J., et al. (2016). Treating cattle with antibiotics affects greenhouse gas emissions, and microbiota in dung and dung beetles. Proc. Biol. Sci. 283:20160150. doi: 10.1098/rspb.2016.0150.
100. Han, X.-M., Hu, H.-W., Shi, X.-Z., Wang, J.-T., Han, L.-L., Chen, D., et al. (2016). Impacts of reclaimed water irrigation on soil antibiotic resistome in urban parks of Victoria, Australia. Environ. Pollut. 211, 48-57. doi: 10.1016/j.envpol.2015.12.033.
101. Hastings, P. J., Rosenberg, S. M., and Slack, A. (2004). Antibiotic-induced lateral transfer of antibiotic resistance. Trends Microbiol. 12, 401-404. doi: 10.1016/j.tim.2004.07.003.
102. Haznedaroglu, B. Z., Yates, M. V., Maduro, M. F., and Walker, S. L. (2012). Effects of residual antibiotics in groundwater on Salmonella typhimurium: changes in antibiotic resistance, in vivo and in vitro pathogenicity. J. Environ. Monit. 14, 41-47. doi: 10.1039/c1em10723b.
103. Head, M. G., Fitchett, J. R., Cooke, M. K., Wurie, F. B., Hayward, A. C., and Atun, R. (2013). UK investments in global infectious disease research 1997-2010: a case study. Lancet Infect. Dis. 13, 55-64. doi: 10.1016/S1473-3099(12)70261-X.
104. Heuer, H., Schmitt, H., and Smalla, K. (2011). Antibiotic resistance gene spread due to manure application on agricultural fields. Curr. Opin. Microbiol. 14, 236-243. doi: 10.1016/j.mib.2011.04.009.
105. Hirsch, R., Ternes, T., Haberer, K., and Kratz, K. L. (1999). Occurrence of antibiotics in the aquatic environment. Sci. Total Environ. 225, 109-118. doi: 10.1016/S0048-9697(98)00337-4.
106. Hollenbeck, B. L., and Rice, L. B. (2012). Intrinsic and acquired resistance mechanisms in enterococcus. Virulence 3, 421-433. doi: 10.4161/viru.21282.
107. Hörsing, M., Ledin, A., Grabic, R., Fick, J., Tysklind, M., la Cour Jansen, J., et al. (2011). Determination of sorption of seventy-five pharmaceuticals in sewage sludge. Water Res. 45, 4470-4482. doi: 10.1016/j.watres.2011.05.033.
108. Hu, X., Zhou, Q., and Luo, Y. (2010). Occurrence and source analysis of typical veterinary antibiotics in manure, soil, vegetables and groundwater from organic vegetable bases, northern China. Environ. Pollut. 158, 2992-2998. doi: 10.1016/j.envpol.2010.05.023.
109. Hu, Y., Yang, X., Qin, J., Lu, N., Cheng, G., Wu, N., et al. (2013). Metagenome-wide analysis of antibiotic resistance genes in a large cohort of human gut microbiota. Nat. Commun. 4:2151. doi: 10.1038/ncomms3151.
110. Hughes, D., and Andersson, D. I. (2012). Selection of resistance at lethal and non-lethal antibiotic concentrations. Curr. Opin. Microbiol. 15, 555-560. doi: 10.1016/j.mib.2012.07.005.
111. Huijbers, P. M. C., Blaak, H., de Jong, M. C. M., Graat, E. A. M., Vandenbroucke-Grauls, C. M. J. E., and de Roda Husman, A. M. (2015). Role of the environment in the transmission of antimicrobial resistance to humans: a review. Environ. Sci. Technol. 49, 11993-12004. doi: 10.1021/acs.est.5b02566.
112. Isidori, M., Lavorgna, M., Nardelli, A., Pascarella, L., and Parrella, A. (2005). Toxic and genotoxic evaluation of six antibiotics on non-target organisms. Sci. Total Environ. 346, 87-98. doi: 10.1016/j.scitotenv.2004.11.017.
113. Jechalke, S., Heuer, H., Siemens, J., Amelung, W., and Smalla, K. (2014). Fate and effects of veterinary antibiotics in soil. Trends Microbiol. 22, 536-545. doi: 10.1016/j.tim.2014.05.005.
114. Jjemba, P. K. (2002). The potential impact of veterinary and human therapeutic agents in manure and biosolids on plants grown on arable land: a review. Agric. Ecosyst. Environ. 93, 267-278. doi: 10.1016/S0167-8809(01)00350-4.
115. Johnson, A. C., and Sumpter, J. P. (2016). Are we going about chemical risk assessment for the aquatic environment the wrong way? Environ. Toxicol. Chem. 35, 1609-1616. doi: 10.1002/etc.3441.
116. Johnson, C. M., and Grossman, A. D. (2015). Integrative and conjugative elements (ICEs): what they do and how they work. Annu. Rev. Genet. 49, 577-601. doi: 10.1146/annurev-genet-112414-055018.
117. Johnson, T. A., Stedtfeld, R. D., Wang, Q., Cole, J. R., Hashsham, S. A., Looft, T., et al. (2016). Clusters of antibiotic resistance genes enriched together stay together in swine agriculture. MBio 7:e02214-15. doi: 10.1128/mBio.02214-15.
118. Johnston, D., Potter, H., Jones, C., Rolley, S., Watson, I., and Pritchard, J. (2008). Abandoned Mines and the Water Environment. Bristol: Environment Agency Science Project SC030136/SR41.
119. Kahrilas, G. A., Blotevogel, J., Stewart, P. S., and Borch, T. (2015). Biocides in hydraulic fracturing fluids: a critical review of their usage, mobility, degradation, and toxicity. Environ. Sci. Technol. 49, 16-32. doi: 10.1021/es503724k.
120. Kang, D. H., Gupta, S., Rosen, C., Fritz, V., Singh, A., Chander, Y., et al. (2013). Antibiotic uptake by vegetable crops from manure-applied soils. J. Agric. Food Chem. 61, 9992-10001. doi: 10.1021/jf404045m.
121. Karvelas, M., Katsoyiannis, A., and Samara, C. (2003). Occurrence and fate of heavy metals in the wastewater treatment process. Chemosphere 53, 1201-1210. doi: 10.1016/S0045-6535(03)00591-5.
122. Kelly, R., Zoubiane, G., Walsh, D., Ward, R., and Goossens, H. (2016). Public funding for research on antibacterial resistance in the JPIAMR countries, the European Commission, and related European Union agencies: a systematic observational analysis. Lancet Infect. Dis. 16, 431-440. doi: 10.1016/S1473-3099(15)00350-3.
123. Khan, R. A., and Thulin, J. (1991). Influence of pollution on parasites of aquatic animals. Adv. Parasitol. 30, 201-238. doi: 10.1016/S0065-308X(08)60309-7.
124. Khanna, T., Friendship, R., Dewey, C., and Weese, J. S. (2008). Methicillin resistant Staphylococcus aureus colonization in pigs and pig farmers. Vet. Microbiol. 128, 298-303. doi: 10.1016/j.vetmic.2007.10.006.
125. Kiesecker, J. M. (2002). Synergism between trematode infection and pesticide exposure: a link to amphibian limb deformities in nature? Proc. Natl. Acad. Sci. U.S.A. 99, 9900-9904. doi: 10.1073/pnas.152098899.
126. Kinney, C. A., Furlong, E. T., Kolpin, D. W., Burkhardt, M. R., Zaugg, S. D., Werner, S. L., et al. (2008). Bioaccumulation of pharmaceuticals and other anthropogenic waste indicators in earthworms from agricultural soil amended with biosolid or swine manure. Environ. Sci. Technol. 42, 1863-1870. doi: 10.1021/es702304c.
127. Kinney, C. A., Furlong, E. T., Werner, S. L., and Cahill, J. D. (2006). Presence and distribution of wastewater-derived pharmaceuticals in soil irrigated with reclaimed water. Environ. Toxicol. Chem. 25, 317-326. doi: 10.1897/05-187R.1.
128. Klous, G., Huss, A., Heederik, D. J. J., and Coutinho, R. A. (2016). Human-livestock contacts and their relationship to transmission of zoonotic pathogens, a systematic review of literature. One Health 2, 65-76. doi: 10.1016/j.onehlt.2016.03.001.
129. Knapp, C. W., Dolfing, J., Ehlert, P. A. I., and Graham, D. W. (2010). Evidence of increasing antibiotic resistance gene abundances in archived soils since 1940. Environ. Sci. Technol. 44, 580-587. doi: 10.1021/es901221x.
130. Kohanski, M. A., DePristo, M. A., and Collins, J. J. (2010). Sublethal antibiotic treatment leads to multidrug resistance via radical-induced mutagenesis. Mol. Cell. 37, 311-320. doi: 10.1016/j.molcel.2010.01.003.
131. Kong, W.-D., Zhu, Y.-G., Fu, B.-J., Marschner, P., and He, J.-Z. (2006). The veterinary antibiotic oxytetracycline and Cu influence functional diversity of the soil microbial community. Environ. Pollut. 143, 129-137. doi: 10.1016/j.envpol.2005.11.003.
132. Kotnik, T. (2013). Lightning-triggered electroporation and electrofusion as possible contributors to natural horizontal gene transfer. Phys. Life Rev. 10, 351-370. doi: 10.1016/j.plrev.2013.05.001.
133. Kümmerer, K. (2009). Antibiotics in the aquatic environment-a review-part I. Chemosphere 75, 417-434. doi: 10.1016/j.chemosphere.2008.11.086.
134. Kyselková, M., Jirout, J., Vrchotová, N., Schmitt, H., and Elhottová, D. (2015). Spread of tetracycline resistance genes at a conventional dairy farm. Front. Microbiol. 6:536. doi: 10.3389/fmicb.2015.00536.
135. Larsson, D. G. J. (2014). Pollution from drug manufacturing: review and perspectives. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 369:20130571. doi: 10.1098/rstb.2013.0571.
136. Leonard, A. F. C., Zhang, L., Balfour, A. J., Garside, R., and Gaze, W. H. (2015). Human recreational exposure to antibiotic resistant bacteria in coastal bathing waters. Environ. Int. 82, 92-100. doi: 10.1016/j.envint.2015.02.013.
137. Levy, S. B. (2002). Active e?ux, a common mechanism for biocide and antibiotic resistance. J. Appl. Microbiol. 92(Suppl.), 65S-71S. doi: 10.1046/j.1365-2672.92.5s1.4.x.
138. Li, B., and Zhang, T. (2010). Biodegradation and adsorption of antibiotics in the activated sludge process. Environ. Sci. Technol. 44, 3468-3473. doi: 10.1021/es903490h.
139. Li, W., Shi, Y., Gao, L., Liu, J., and Cai, Y. (2013). Occurrence, distribution and potential affecting factors of antibiotics in sewage sludge of wastewater treatment plants in China. Sci. Total Environ. 44, 306-313. doi: 10.1016/j.scitotenv.2012.12.050.
140. Liu, A., Fong, A., Becket, E., Yuan, J., Tamae, C., Medrano, L., et al. (2011). Selective advantage of resistant strains at trace levels of antibiotics: a simple and ultrasensitive color test for detection of antibiotics and genotoxic agents. Antimicrob. Agents Chemother. 55, 1204-1210. doi: 10.1128/AAC.01182-10.
141. Liu, J., Zhao, Z., Orfe, L., Subbiah, M., and Call, D. R. (2016). Soil-borne reservoirs of antibiotic-resistant bacteria are established following therapeutic treatment of dairy calves. Environ. Microbiol. 18, 557-564. doi: 10.1111/1462-2920.13097.
142. Looft, T., and Allen, H. K. (2012). Collateral effects of antibiotics on mammalian gut microbiomes. Gut Microbes 3, 463-467. doi: 10.4161/gmic.21288.
143. Loos, R., Locoro, G., Comero, S., Contini, S., Schwesig, D., Werres, F., et al. (2010). Pan-European survey on the occurrence of selected polar organic persistent pollutants in ground water. Water Res. 44, 4115-4126. doi: 10.1016/j.watres.2010.05.032.
144. Lopatkin, A. J., Huang, S., Smith, R. P., Srimani, J. K., Sysoeva, T. A., Bewick, S., et al. (2016). Antibiotics as a selective driver for conjugation dynamics. Nat. Microbiol. 1:16044. doi: 10.1038/nmicrobiol.2016.44.
145. Lundström, S. V., Östman, M., Bengtsson-Palme, J., Rutgersson, C., Thoudal, M., Sircar, T., et al. (2016). Minimal selective concentrations of tetracycline in complex aquatic bacterial biofilms. Sci. Total Environ. 553, 587-595. doi: 10.1016/j.scitotenv.2016.02.103.
146. Luo, Y., Guo, W., Ngo, H. H., Nghiem, L. D., Hai, F. I., Zhang, J., et al. (2014). A review on the occurrence of micropollutants in the aquatic environment and their fate and removal during wastewater treatment. Sci. Total Environ. 47, 619-641. doi: 10.1016/j.scitotenv.2013.12.065.
147. Maher, M. C., Alemayehu, W., Lakew, T., Gaynor, B. D., Haug, S., Cevallos, V., et al. (2012). The fitness cost of antibiotic resistance in Streptococcus pneumoniae: insight from the field. PLoS ONE 7:e29407. doi: 10.1371/journal.pone.0029407.
148. Manamsa, K., Crane, E., Stuart, M., Talbot, J., Lapworth, D., and Hart, A. (2016). A national-scale assessment of micro-organic contaminants in groundwater of England and Wales. Sci. Total Environ. 568, 712-726. doi: 10.1016/j.scitotenv.2016.03.017.
149. McBain, A. J., Rickard, A. H., and Gilbert, P. (2002). Possible implications of biocide accumulation in the environment on the prevalence of bacterial antibiotic resistance. J. Ind. Microbiol. Biotechnol. 29, 326-330. doi: 10.1038/sj.jim.7000324.
150. McClellan, K., and Halden, R. U. (2010). Pharmaceuticals and personal care products in archived U.S. biosolids from the 2001 EPA national sewage sludge survey. Water Res. 44, 658-668. doi: 10.1016/j.watres.2009.12.032.
151. McDonalds Corporation (2015). McDonald's Global Vision for Antimicrobial Stewardship in Food Animals. Available at: http://www.aboutmcdonalds.com/content/dam/AboutMcDonalds/Sustainability/Antimicrobial_Stewardship_Vision.pdf.
152. McEachran, A. D., Blackwell, B. R., Hanson, J. D., Wooten, K. J., Mayer, G. D., Cox, S. B., et al. (2015). Antibiotics, bacteria, and antibiotic resistance genes: aerial transport from cattle feed yards via particulate matter. Environ. Health Perspect. 123, 337-343. doi: 10.1289/ehp.1408555.
153. Medical Research Council (2014). New Science Minister Announces "War Cabinet" to Tackle Antimicrobial Resistance on All Fronts-News-Medical Research Council. New Science Minister Announces "War Cabinet" to Tackle Antimicrobial Resistance on All Fronts-News-Medical Research Council. Available at: http://www.mrc.ac.uk/news/browse/war-cabinet-to-tackle-amr/[accessed July 5, 2016].
154. Mitchell, S. M., Subbiah, M., Ullman, J. L., Frear, C., and Call, D. R. (2015). Evaluation of 27 different biochars for potential sequestration of antibiotic residues in food animal production environments. J. Environ. Chem. Eng. 3, 162-169. doi: 10.1016/j.jece.2014.11.012.
155. Na, G., Fang, X., Cai, Y., Ge, L., Zong, H., Yuan, X., et al. (2013). Occurrence, distribution, and bioaccumulation of antibiotics in coastal environment of Dalian China. Mar. Pollut. Bull. 69, 233-237. doi: 10.1016/j.marpolbul.2012.12.028.
156. Newton, R. J., McLellan, S. L., Dila, D. K., Vineis, J. H., Morrison, H. G., Eren, A. M., et al. (2015). Sewage reflects the microbiomes of human populations. MBio 6:e02574. doi: 10.1128/mBio.0257414.
157. Nicholson, F., Chambers, B., Williams, J., and Unwin, R. (1999). Heavy metal contents of livestock feeds and animal manures in England and Wales. Bioresour. Technol. 70, 23-31. doi: 10.1016/S0960-8524(99)00017-6.
158. Nicholson, F. A., Smith, S. R., Alloway, B. J., Carlton-Smith, C., and Chambers, B. J. (2003). An inventory of heavy metals inputs to agricultural soils in England and Wales. Sci. Total Environ. 311, 205-219. doi: 10.1016/S0048-9697(03)00139-6.
159. Nies, D. H. (2003). E?ux-mediated heavy metal resistance in prokaryotes. FEMS Microbiol. Rev. 27, 313-339. doi: 10.1016/S0168-6445(03)00048-2.
160. Novais, C., Freitas, A. R., Silveira, E., Antunes, P., Silva, R., Coque, T. M., et al. (2013). Spread of multidrug-resistant Enterococcus to animals and humans: an underestimated role for the pig farm environment. J. Antimicrob Chemother. 68, 2746-2754. doi: 10.1093/jac/dkt289.
161. OIE-World Organization for Animal Health (2015). OIE List of Antimicrobial Agents of Veterinary Importance. Paris: OIE-World Organization for Animal Health.
162. Olaniran, A. O., Balgobind, A., and Pillay, B. (2013). Bioavailability of heavy metals in soil: impact on microbial biodegradation of organic compounds and possible improvement strategies. Int. J. Mol. Sci. 14, 10197-10228. doi: 10.3390/ijms140510197.
163. O'Neill, J., and The Review on Antimicrobial Resistance (2015). Antimicrobials in Agriculture and the Environment: Reducing Unnecessary Use and Waste. Available at: http://amr-review.org/sites/default/files/Antimicrobials%20in%20agriculture%20and%20the%20environment%20-%20Reducing%20unnecessary%20use%20and%20waste.pdf.
164. O'Neill, J., and The Review on Antimicrobial Resistance (2016). Tackling Drug-Resistant Infections Globally: Final Report and Recommendations. Available at: http://amr-review.org/sites/default/files/160518_Final%20paper_with%20cover.pdf.
165. Otterpohl, R., Braun, U., and Oldenburg, M. (2004). Innovative technologies for decentralised water-, wastewater and biowaste management in urban and peri-urban areas. Water Sci. Technol. 48, 23-32.
166. Owen, R., and Jobling, S. (2012). Environmental science: the hidden costs of flexible fertility. Nature 485:441. doi: 10.1038/485441a.
167. Pal, C., Bengtsson-Palme, J., Kristiansson, E., and Larsson, D. G. J. (2015). Co-occurrence of resistance genes to antibiotics, biocides and metals reveals novel insights into their co-selection potential. BMC Genomics 16:964. doi: 10.1186/s12864-015-2153-5.
168. Pal, C., Bengtsson-Palme, J., Rensing, C., Kristiansson, E., and Larsson, D. G. J. (2014). BacMet: antibacterial biocide and metal resistance genes database. Nucleic Acids Res. 42, D737-D743. doi: 10.1093/nar/gkt1252.
169. Pan, M., and Chu, L. M. (2016). Phytotoxicity of veterinary antibiotics to seed germination and root elongation of crops. Ecotoxicol. Environ. Saf. 126, 228-237. doi: 10.1016/j.ecoenv.2015.12.027.
170. Percival, S. L., Bowler, P. G., and Russell, D. (2005). Bacterial resistance to silver in wound care. J. Hosp. Infect. 60, 1-7. doi: 10.1016/j.jhin.2004.11.014.
171. Perry, J. A., and Wright, G. D. (2013). The antibiotic resistance "mobilome": searching for the link between environment and clinic. Front. Microbiol. 4:138. doi: 10.3389/fmicb.2013.00138.
172. Piddock, L. J. V. (2016). Reflecting on the final report of the O'Neill Review on Antimicrobial Resistance. Lancet Infect Dis. 16, 767-768. doi: 10.1016/S1473-3099(16)30127-X.
173. Polesel, F., Lehnberg, K., Dott, W., Trapp, S., Thomas, K. V., and Plósz, B. G. (2015). Factors influencing sorption of ciprofloxacin onto activated sludge: experimental assessment and modelling implications. Chemosphere 119, 105-111. doi: 10.1016/j.chemosphere.2014.05.048.
174. Prudhomme, C., Young, A., Watts, G., Haxton, T., Crooks, S., Williamson, J., et al. (2012). The drying up of Britain? A national estimate of changes in seasonal river flows from 11 regional climate model simulations. Hydrol. Process. 26, 1115-1118. doi: 10.1002/hyp.8434.
175. Public Health England (2013). The Animal By-Products (Enforcement) (England) Regulations 2013. Available at: http://www.legislation.gov.uk/uksi/2013/2952/pdfs/uksi_20132952_en.pdf.
176. Public Health England (2014). English Surveillance Programme for Antimicrobial Utilisation and Resistance (ESPAUR). Available at: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/362374/ESPAUR_Report_2014__3_.pdf.
177. Public Health England (2015). UK One Health Report: Joint Report on Human and Animal Antibiotic Use, Sales and Resistance, 2013. Available at: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/447319/One_Health_Report_July2015.pdf.
178. Public Health England and Wales, and Public Health Scotland (1989). The Sludge (Use in Agriculture) Regulations 1989. Available at: http://legislation.data.gov.uk/uksi/1989/1263/made/data.htm?wrap=true.
179. Ramos, J. L., Duque, E., Gallegos, M.-T., Godoy, P., Ramos-Gonzalez, M. I., Rojas, A., et al. (2002). Mechanisms of solvent tolerance in gram-negative bacteria. Annu. Rev. Microbiol. 56, 743-768. doi: 10.1146/annurev.micro.56.012302.161038.
180. Rico, A., Dimitrov, M. R., Van Wijngaarden, R. P. A., Satapornvanit, K., Smidt, H., and Van den Brink, P. J. (2014). Effects of the antibiotic enrofloxacin on the ecology of tropical eutrophic freshwater microcosms. Aquat. Toxicol. 147, 92-104. doi: 10.1016/j.aquatox.2013.12.008.
181. Rivera-Utrilla, J., Sánchez-Polo, M., Ferro-García, M. Á, Prados-Joya, G., and Ocampo-Pérez, R. (2013). Pharmaceuticals as emerging contaminants and their removal from water. A review. Chemosphere 93, 1268-1287. doi: 10.1016/j.chemosphere.2013.07.059.
182. Roberts, A. P., and Mullany, P. (2011). Tn916-like genetic elements: a diverse group of modular mobile elements conferring antibiotic resistance. FEMS Microbiol. Rev. 35, 856-871. doi: 10.1111/j.1574-6976.2011.00283.x.
183. Rosendahl, I., Siemens, J., Kindler, R., Groeneweg, J., Zimmermann, J., Czerwinski, S., et al. (2012). Persistence of the fluoroquinolone antibiotic difloxacin in soil and lacking effects on nitrogen turnover. J. Environ. Qual. 41, 1275-1283. doi: 10.2134/jeq2011.0459.
184. Roux, D., Danilchanka, O., Guillard, T., Cattoir, V., Aschard, H., Fu, Y., et al. (2015). Fitness cost of antibiotic susceptibility during bacterial infection. Sci. Transl. Med. 7:297ra114. doi: 10.1126/scitranslmed.aab1621.
185. Russell, A. D. (2003). Biocide use and antibiotic resistance: the relevance of laboratory findings to clinical and environmental situations. Lancet Infect. Dis. 3, 794-803. doi: 10.1016/S1473-3099(03)00833-8.
186. Safrany, N., and Monnet, D. L. (2012). Antibiotics obtained without a prescription in Europe. Lancet Infect. Dis. 12, 182-183. doi: 10.1016/S1473-3099(12)70017-8.
187. Samuelsen, O. B., Torsvik, V., and Ervik, A. (1992). Long-range changes in oxytetracycline concentration and bacterial resistance toward oxytetracycline in a fish farm sediment after medication. Sci. Total Environ. 114, 25-36. doi: 10.1016/0048-9697(92)90411-K.
188. Sandaa, R.-A., Torsvik, V. L., and Goksøyr, J. (1992). Transferable drug resistance in bacteria from fish-farm sediments. Can. J. Microbiol. 38, 1061-1065. doi: 10.1139/m92-174.
189. Sarmah, A. K., Meyer, M. T., and Boxall, A. B. A. (2006). A global perspective on the use, sales, exposure pathways, occurrence, fate and effects of veterinary antibiotics (VAs) in the environment. Chemosphere 65, 725-759. doi: 10.1016/j.chemosphere.2006.03.026.
190. Sattar, S. A., Tetro, J. A., and Springthorpe, V. S. (2007). "Effects of environmental chemicals and the host-pathogen relationship: are there any negative consequences for human health?," in New Biocides Development, ed. P. C. Zhu (Washington, DC: American Chemical Society), 2-30. doi: 10.1021/bk-2007-0967.ch001.
191. Schmidt, A. S., Bruun, M. S., Dalsgaard, I., and Larsen, J. L. (2001). Incidence, distribution, and spread of tetracycline resistance determinants and integron-associated antibiotic resistance genes among motile aeromonads from a fish farming environment. Appl. Environ. Microbiol. 67, 5675-5682. doi: 10.1128/AEM.67.12.5675-5682.2001.
192. Schmidt, A. S., Bruun, M. S., Dalsgaard, I., Pedersen, K., and Larsen, J. L. (2000). Occurrence of antimicrobial resistance in fish-pathogenic and environmental bacteria associated with four danish rainbow trout farms. Appl. Environ. Microbiol. 66, 4908-4915. doi: 10.1128/AEM.66.11.4908-4915.2000.
193. Selck, H., Handy, R. D., Fernandes, T. F., Klaine, S. J., and Petersen, E. J. (2016). Nanomaterials in the aquatic environment: a European Union-United States perspective on the status of ecotoxicity testing, research priorities, and challenges ahead. Environ. Toxicol. Chem. 35, 1055-1067. doi: 10.1002/etc.3385.
194. Sifaoui, F., Arthur, M., Rice, L., and Gutmann, L. (2001). Role of penicillin-binding protein 5 in expression of ampicillin resistance and peptidoglycan structure in Enterococcus faecium. Antimicrob. Agents Chemother. 45, 2594-2597. doi: 10.1128/AAC.45.9.2594-2597.2001.
195. Siguier, P., Gourbeyre, E., and Chandler, M. (2014). Bacterial insertion sequences: their genomic impact and diversity. FEMS Microbiol. Rev. 38, 865-891. doi: 10.1111/1574-6976.12067.
196. Singer, A. C., Colizza, V., Schmitt, H., Andrews, J., Balcan, D., Huang, W. E., et al. (2011). Assessing the ecotoxicologic hazards of a pandemic influenza medical response. Environ. Health Perspect. 119, 1084-1090. doi: 10.1289/ehp.1002757.
197. Smith, S. R. (2009). A critical review of the bioavailability and impacts of heavy metals in municipal solid waste composts compared to sewage sludge. Environ. Int. 35, 142-156. doi: 10.1016/j.envint.2008.06.009.
198. Smith, T. C., Gebreyes, W. A., Abley, M. J., Harper, A. L., Forshey, B. M., Male, M. J., et al. (2013). Methicillin-resistant Staphylococcus aureus in pigs and farm workers on conventional and antibiotic-free swine farms in the USA. PLoS ONE 8:e63704. doi: 10.1371/journal.pone.0063704.
199. Snelders, E., van der Lee, H. A. L., Kuijpers, J., Rijs, A. J. M. M., Varga, J., Samson, R. A., et al. (2008). Emergence of azole resistance in Aspergillus fumigatus and spread of a single resistance mechanism. PLoS Med. 5:e219. doi: 10.1371/journal.pmed.0050219.
200. Stuart, M., Lapworth, D., Crane, E., and Hart, A. (2012). Review of risk from potential emerging contaminants in UK groundwater. Sci. Total Environ. 416, 1-21. doi: 10.1016/j.scitotenv.2011.11.072.
201. Su, J.-Q., Wei, B., Ou-Yang, W.-Y., Huang, F.-Y., Zhao, Y., Xu, H.-J., et al. (2015). Antibiotic resistome and its association with bacterial communities during sewage sludge composting. Environ. Sci. Technol. 49, 7356-7363. doi: 10.1021/acs.est.5b01012.
202. Subirats, J., Sànchez-Melsió, A., Borrego, C. M., Balcázar, J. L., and Simonet, P. (2016). Metagenomic analysis reveals that bacteriophages are reservoirs of antibiotic resistance genes. Int. J. Antimicrob Agents. 48, 163-167. doi: 10.1016/j.ijantimicag.2016.04.028.
203. Subway Ip, Inc. (2016). SUBWAY® Sandwich Shop Introduces New Rotisserie-Style Chicken Raised without Antibiotics. Available at: http://www.prnewswire.com/news-releases/subway-sandwich-shop-introduces-new-rotisserie-style-chicken-raised-without-antibiotics-300226838.html.
204. Sui, Q., Cao, X., Lu, S., Zhao, W., Qiu, Z., and Yu, G. (2015). Occurrence, sources and fate of pharmaceuticals and personal care products in the groundwater: a review. Emerg. Contaminants. 1, 14-24. doi: 10.1016/j.emcon.2015.07.001.
205. Sumpter, J. P. (2009). Protecting aquatic organisms from chemicals: the harsh realities. Philos. Trans. Math Phys. Eng. Sci. 367, 3877-3894. doi: 10.1098/rsta.2009.0106.
206. Szczepanowski, R., Braun, S., Riedel, V., Schneiker, S., Krahn, I., Pühler, A., et al. (2005). The 120 592 bp IncF plasmid pRSB107 isolated from a sewage-treatment plant encodes nine different antibiotic-resistance determinants, two iron-acquisition systems and other putative virulence-associated functions. Microbiology (Reading, Engl.) 151, 1095-1111. doi: 10.1099/mic.0.27773-0.
207. Taco Bell Corp (2016). Statement Regarding Antibiotics-Taco Bell. Available at: https://www.tacobell.com/news/statement-regarding-antibiotics.
208. Tasho, R. P., and Cho, J. Y. (2016). Veterinary antibiotics in animal waste, its distribution in soil and uptake by plants: a review. Sci. Total Environ. 56, 366-376. doi: 10.1016/j.scitotenv.2016.04.140.
209. Thanner, S., Drissner, D., and Walsh, F. (2016). Antimicrobial resistance in agriculture. MBio 7:e2227-15. doi: 10.1128/mBio.02227-15.
210. Tipping, E., and Lofts, S. (2013). Metal mixture toxicity to aquatic biota in laboratory experiments: application of the WHAM-FTOX model. Aquat. Toxicol. 14, 114-122. doi: 10.1016/j.aquatox.2013.08.003.
211. Tyson Fresh Meat Inc. (2014). Tyson Fresh Meats Launches Open PrairieTM Natural Pork. Available at: http://www.tysonfoods.com/Media/News-Releases/2016/02/Natural-Pork-Launch.aspx (accessed March 11, 2016).
212. Udikovic-Kolic, N., Wichmann, F., Broderick, N. A., and Handelsman, J. (2014). Bloom of resident antibiotic-resistant bacteria in soil following manure fertilization. Proc. Natl. Acad. Sci. U.S.A. 111, 15202-15207. doi: 10.1073/pnas.1409836111.
213. UNESCO-IHE (2011). National Water Footprint Accounts: The Green, Blue and Grey Water Footprint of Production and Consumption. Vol. 1. Main Report. Research Report Series No. 50. Enschede: University of Twente. Available at: https://www.ice.org.uk/getattachment/media-and-policy/policy/state-of-the-nation-water-2012/EC01408_SoN-Water_Low-Res_v2_aw.pdf.aspx.
214. USDA (2010). Overview of the United States Cattle Industry. Available at: http://usda.mannlib.cornell.edu/usda/nass/USCatSup//2010s/2010/USCatSup-12-17-2010.pdf.
215. USDA (2015a). Overview of the United States Hog Industry. Available at: http://usda.mannlib.cornell.edu/usda/current/hogview/hogview-10-29-2015.pdf.
216. USDA (2015b). Poultry-Production and Value 2014 Summary. Available at: http://www.usda.gov/nass/PUBS/TODAYRPT/plva0415.pdf.
217. Usui, M., Shirakawa, T., Fukuda, A., and Tamura, Y. (2015). The role of flies in disseminating plasmids with antimicrobial-resistance genes between farms. Microb. Drug Resist. 21, 562-569. doi: 10.1089/mdr.2015.0033.
218. Van Boeckel, T. P., Gandra, S., Ashok, A., Caudron, Q., Grenfell, B. T., Levin, S. A., et al. (2014). Global antibiotic consumption 2000 to 2010: an analysis of national pharmaceutical sales data. Lancet Infect. Dis. 14, 742-750. doi: 10.1016/S1473-3099(14)70780-7.
219. Verlicchi, P., and Zambello, E. (2016). Predicted and measured concentrations of pharmaceuticals in hospital e?uents. Examination of the strengths and weaknesses of the two approaches through the analysis of a case study. Sci. Total Environ. 565, 82-94. doi: 10.1016/j.scitotenv.2016.04.165.
220. Versporten, A., Bolokhovets, G., Ghazaryan, L., Abilova, V., Pyshnik, G., Spasojevic, T., et al. (2014). Antibiotic use in eastern Europe: a cross-national database study in coordination with the WHO Regional Office for Europe. Lancet Infect. Dis. 14, 381-387. doi: 10.1016/S1473-3099(14)70071-4.
221. Verweij, P. E., Snelders, E., Kema, G. H. J., Mellado, E., and Melchers, W. J. G. (2009). Azole resistance in Aspergillus fumigatus: a side-effect of environmental fungicide use? Lancet Infect Dis. 9, 789-795. doi: 10.1016/S1473-3099(09)70265-8.
222. Veterinary Medicines Directorate (2014). UK Veterinary Antibiotic Resistance and Sales Surveillance (UK-VARSS 2014).
223. Waara, K.-O. (1992). Effects of copper, cadmium, lead and zinc on nitrate reduction in a synthetic water medium and lake water from Northern Sweden. Water Res. 26, 355-364. doi: 10.1016/0043-1354(92)90032-Y.
224. Wales, A. D., and Davies, R. H. (2015). Co-selection of resistance to antibiotics, biocides and heavy metals, and its relevance to foodborne pathogens. Antibiotics (Basel) 4, 567-604. doi: 10.3390/antibiotics4040567.
225. Walter, I., Martínez, F., and Cala, V. (2006). Heavy metal speciation and phytotoxic effects of three representative sewage sludges for agricultural uses. Environ. Pollut. 139, 507-514. doi: 10.1016/j.envpol.2005.05.020.
226. Wang, F.-H., Qiao, M., Chen, Z., Su, J.-Q., and Zhu, Y.-G. (2015). Antibiotic resistance genes in manure-amended soil and vegetables at harvest. J. Hazard. Mater. 299, 215-221. doi: 10.1016/j.jhazmat.2015.05.028.
227. Wardle, D. A., Bardgett, R. D., Klironomos, J. N., Setälä, H., van der Putten, W. H., and Wall, D. H. (2004). Ecological linkages between aboveground and belowground biota. Science 304, 1629-1633. doi: 10.1126/science.1094875.
228. Warnes, S. L., Highmore, C. J., and Keevil, C. W. (2012). Horizontal transfer of antibiotic resistance genes on abiotic touch surfaces: implications for public health. MBio 3:e489-12. doi: 10.1128/mBio.00489-12.
229. Water UK (2010). Recycling of Biosolids to Agricultural Land. Available at: https://dl.dropboxusercontent.com/u/299993612/Publications/Reports/Waste%20recycling/recycling-biosolids-to-agricultural-land-january-2010-final.pdf.
230. Webber, M. A., Whitehead, R. N., Mount, M., Loman, N. J., Pallen, M. J., and Piddock, L. J. V. (2015). Parallel evolutionary pathways to antibiotic resistance selected by biocide exposure. J. Antimicrob Chemother. 70, 2241-2248. doi: 10.1093/jac/dkv109.
231. Weir, M., Rajic, A., Dutil, L., Uhland, C., and Bruneau, N. (2012). Zoonotic bacteria and antimicrobial resistance in aquaculture: opportunities for surveillance in Canada. Can. Vet. J. 53, 619-622.
232. Wesgate, R., Grasha, P., and Maillard, J.-Y. (2016). Use of a predictive protocol to measure the antimicrobial resistance risks associated with biocidal product usage. Am. J. Infect. Control 44, 458-464. doi: 10.1016/j.ajic.2015.11.009.
233. Wichmann, F., Udikovic-Kolic, N., Andrew, S., and Handelsman, J. (2014). Diverse antibiotic resistance genes in dairy cow manure. MBio 5:e01017. doi: 10.1128/mBio.01017-13.
234. Wiedenbeck, J., and Cohan, F. M. (2011). Origins of bacterial diversity through horizontal genetic transfer and adaptation to new ecological niches. FEMS Microbiol. Rev. 35, 957-976. doi: 10.1111/j.1574-6976.2011.00292.x.
235. Winder, L., Merrington, G., and Green, I. (1999). The tri-trophic transfer of Zn from the agricultural use of sewage sludge. Sci. Total Environ. 229, 73-81. doi: 10.1016/S0048-9697(99)00070-4.
236. Woolhouse, M., and Farrar, J. (2014). Policy: an intergovernmental panel on antimicrobial resistance. Nature 509, 555-557. doi: 10.1038/509555a.
237. Woolhouse, M., Ward, M., van Bunnik, B., and Farrar, J. (2015). Antimicrobial resistance in humans, livestock and the wider environment. Philos. Trans. R. Soc. Lond. B Biol. Sci. 370:20140083. doi: 10.1098/rstb.2014.0083.
238. World Health Organisation (2015). Global Action Plan on Antimicrobial Resistance. Available at: http://apps.who.int/iris/bitstream/10665/193736/1/9789241509763\_eng.pdf?ua=1.
239. Wozniak, R. A. F., and Waldor, M. K. (2010). Integrative and conjugative elements: mosaic mobile genetic elements enabling dynamic lateral gene flow. Nat. Rev. Microbiol. 8, 552-563. doi: 10.1038/nrmicro2382.
240. Wulf, M. W. H., Sørum, M., van Nes, A., Skov, R., Melchers, W. J. G., Klaassen, C. H. W., et al. (2008). Prevalence of methicillin-resistant Staphylococcus aureus among veterinarians: an international study. Clin. Microbiol. Infect. 14, 29-34. doi: 10.1111/j.1469-0691.2007.01873.x.
241. Xu, J., Xu, Y., Wang, H., Guo, C., Qiu, H., He, Y., et al. (2015). Occurrence of antibiotics and antibiotic resistance genes in a sewage treatment plant and its e?uent-receiving river. Chemosphere 119, 1379-1385. doi: 10.1016/j.chemosphere.2014.02.040.
242. Yamamoto, T., Tamura, Y., and Yokota, T. (1988). Antiseptic and antibiotic resistance plasmid in Staphylococcus aureus that possesses ability to confer chlorhexidine and acrinol resistance. Antimicrob. Agents Chemother. 32, 932-935. doi: 10.1128/AAC.32.6.932.
243. Yang, S.-F., Lin, C.-F., Wu, C.-J., Ng, K.-K., Lin, A. Y.-C., and Hong, P.-K. A. (2012). Fate of sulfonamide antibiotics in contact with activated sludge-sorption and biodegradation. Water Res. 46, 1301-1308. doi: 10.1016/j.watres.2011.12.035.
244. Yang, Y., Li, B., Zou, S., Fang, H. H. P., and Zhang, T. (2014). Fate of antibiotic resistance genes in sewage treatment plant revealed by metagenomic approach. Water Res. 62, 97-106. doi: 10.1016/j.watres.2014.05.019.
245. Yergeau, E., Lawrence, J. R., Waiser, M. J., Korber, D. R., and Greer, C. W. (2010). Metatranscriptomic analysis of the response of river biofilms to pharmaceutical products, using anonymous DNA microarrays. Appl. Environ. Microbiol. 76, 5432-5439. doi: 10.1128/AEM.00873-10.
246. Yergeau, E., Sanschagrin, S., Waiser, M. J., Lawrence, J. R., and Greer, C. W. (2012). Sub-inhibitory concentrations of different pharmaceutical products affect the meta-transcriptome of river biofilm communities cultivated in rotating annular reactors. Environ. Microbiol. Rep. 4, 350-359. doi: 10.1111/j.1758-2229.2012.00341.x.
247. Zhang, L., Huang, Y., Zhou, Y., Buckley, T., and Wang, H. H. (2013). Antibiotic administration routes significantly influence the levels of antibiotic resistance in gut microbiota. Antimicrob. Agents Chemother. 57, 3659-3666. doi: 10.1128/AAC.00670-13.
248. Zhang, Q.-Q., Ying, G.-G., Pan, C.-G., Liu, Y.-S., and Zhao, J.-L. (2015). Comprehensive evaluation of antibiotics emission and fate in the river basins of China: source analysis, multimedia modeling, and linkage to bacterial resistance. Environ. Sci. Technol. 49, 6772-6782. doi: 10.1021/acs.est.5b00729.
249. Zhang, X.-X., and Zhang, T. (2011). Occurrence, abundance, and diversity of tetracycline resistance genes in 15 sewage treatment plants across China and other global locations. Environ. Sci. Technol. 45, 2598-2604. doi: 10.1021/es103672x.
250. Zurek, L., and Ghosh, A. (2014). Insects represent a link between food animal farms and the urban environment for antibiotic resistance traits. Appl. Environ. Microbiol. 80, 3562-3567. doi: 10.1128/AEM.00600-14.