Human-use antibacterial residues in the natural environment of China: implication for ecopharmacovigilance

  • Jun Wang
  • Bingshu HeEmail author
  • Xiamin Hu


Antibacterial residues in the natural environment have been of increasing concern due to their impact on bacteria resistance development and toxicity to natural communities and ultimately to public health. China is a large country with high production and consumption of antibacterials for its population growth and economic development in recent years. In this article, we summarized the current situation of human-use antibacterial pollution in Chinese water (wastewaters, natural and drinking waters) and solid matrices (sludge, sediment, and soil) reported in 33 peer-reviewed papers. We found that, although there are adequate wastewater treatment systems in China, human-use antibacterial residues in the natural environment were reported almost throughout the whole country. Three most frequently prescribed classes of antibacterials in China, including quinolones, macrolides, and β-lactam, were also the predominant classes of residues in Chinese environment, manifested as the high concentration and detection frequency. In view of this alarming situation, we have presented that ecopharmacovigilance (EPV) might be implemented in the antibacterial drug administration of China, as the active participation of the pharmaceutical industry and drug regulatory authorities from the diffuse source of antibacterial pollution. Considering EPV experience of developed countries together with the actual conditions of China, we have identified some approaches that can be taken, including:

• Focus on education;

• Further strengthening and persevering the antibacterial stewardship strategies and pharmaceutical take-back programs in China;

• Designing greener antibacterials with better degradability in the environment;

• Implementing environmental risk assessment prior to launch of new drugs;

• Strengthening collaboration in EPV-related areas.


Pharmaceutical residues Antibacterial Ecopharmacovigilance China Environment 


  1. Agunbiade, F. O., & Moodley, B. (2014). Pharmaceuticals as emerging organic contaminants in Umgeni River water system, KwaZulu-Natal, South Africa. Environmental Monitoring and Assessment, 186(11), 7273–7291.CrossRefGoogle Scholar
  2. Ashbolt, N. J., Amézquita, A., Backhaus, T., Borriello, P., Brandt, K. K., Collignon, P., et al. (2013). Human Health Risk Assessment (HHRA) for environmental development and transfer of antibiotic resistance. Environmental Health Perspectives, 121(9), 993–1001.Google Scholar
  3. Boxall, A. B., Rudd, M. A., Brooks, B. W., Caldwell, D. J., Choi, K., Hickmann, S., et al. (2012). Pharmaceuticals and personal care products in the environment: what are the big questions? Environmental Health Perspectives, 120(9), 1221–1229.CrossRefGoogle Scholar
  4. Bueno, M. J., Gomez, M. J., Herrera, S., Hernando, M. D., Agüera, A., & Fernández-Alba, A. R. (2012). Occurrence and persistence of organic emerging contaminants and priority pollutants in five sewage treatment plants of Spain: two years pilot survey monitoring. Environmental Pollution, 164, 267–273.CrossRefGoogle Scholar
  5. Centers for Disease Control and Prevention (CDC) (2013). Antibiotic resistance threats in the United States. -report-2013/
  6. Cha, J. M., Yang, S., & Carlson, K. H. (2006). Trace determination of beta-lactam antibiotics in surface water and urban wastewater using liquid chromatography combined with electrospray tandem mass spectrometry. Journal of Chromatography A, 1115(1-2), 46–57.CrossRefGoogle Scholar
  7. Chen, K., & Zhou, J. L. (2014). Occurrence and behavior of antibiotics in water and sediments from the Huangpu River, Shanghai, China. Chemosphere, 95, 604–612.CrossRefGoogle Scholar
  8. Chen, Y., Yu, G., Cao, Q., Zhang, H., Lin, Q., & Hong, Y. (2013). Occurrence and environmental implications of pharmaceuticals in Chinese municipal sewage sludge. Chemosphere, 93, 1765–1772.CrossRefGoogle Scholar
  9. Chen, C., Li, J., Chen, P., Ding, R., Zhang, P., & Li, X. (2014). Occurrence of antibiotics and antibiotic resistances in soils from wastewater irrigation areas in Beijing and Tianjin, China. Environmental Pollution, 193, 94–101.CrossRefGoogle Scholar
  10. Cheng, D., Liu, X., Wang, L., Gong, W., Liu, G., Fu, W., et al. (2014). Seasonal variation and sediment-water exchange of antibiotics in a shallower large lake in North China. Science of the Total Environment, 476–477, 266–275.CrossRefGoogle Scholar
  11. Diwan, V., Tamhankar, A. J., Khandal, R. K., Sen, S., Aggarwal, M., Marothi, Y., et al. (2010). Antibiotics and antibiotic-resistant bacteria in waters associated with a hospital in Ujjain, India. BMC Public Health, 10, 414.CrossRefGoogle Scholar
  12. Fatta-Kassinos, D., Meric, S., & Nikolaou, A. (2011). Pharmaceutical residues in environmental waters and wastewater: current state of knowledge and future research. Analytical and Bioanalytical Chemistry, 399(1), 251–275.CrossRefGoogle Scholar
  13. Finley, R. L., Collignon, P., Larsson, D. G., McEwen, S. A., Li, X. Z., Gaze, W. H., et al. (2013). The scourge of antibiotic resistance: the important role of the environment. Clinical Infectious Diseases, 57(5), 704–710.CrossRefGoogle Scholar
  14. Gao, L., Shi, Y., Li, W., Niu, H., Liu, J., & Cai, Y. (2012). Occurrence of antibiotics in eight sewage treatment plants in Beijing, China. Chemosphere, 86, 665–671.CrossRefGoogle Scholar
  15. Glassmeyer, S. T., Hinchey, E. K., Boehme, S. E., Daughton, C. G., Ruhoy, I. S., Conerly, O., et al. (2009). Disposal practices for unwanted residential medications in the United States. Environment International, 35(3), 566–572.CrossRefGoogle Scholar
  16. Guerra, P., Kim, M., Shah, A., Alaee, M., & Smyth, S. A. (2014). Occurrence and fate of antibiotic, analgesic/anti-inflammatory, and antifungal compounds in five wastewater treatment processes. Science of the Total Environment, 473–474, 235–243.CrossRefGoogle Scholar
  17. Gulkowska, A., Leung, H. W., So, M. K., Taniyasu, S., Yamashita, N., Yeung, L. W., et al. (2008). Removal of antibiotics from wastewater by sewage treatment facilities in Hong Kong and Shenzhen, China. Water Research, 42(1-2), 395–403.CrossRefGoogle Scholar
  18. Holm, G., Snape, J. R., Murray-Smith, R., Talbot, J., Taylor, D., & Sörme, P. (2013). Implementing ecopharmacovigilance in practice: challenges and potential opportunities. Drug Safety, 36(7), 533–546.CrossRefGoogle Scholar
  19. Hou, D., Wang, Q., Jiang, C., Tian, C., Li, H., & Ji, B. (2014). Evaluation of the short-term effects of antimicrobial stewardship in the intensive care unit at a tertiary hospital in china. PloS One, 9(7), e101447.CrossRefGoogle Scholar
  20. Jiang, L., Hu, X., Yin, D., Zhang, H., & Yu, Z. (2011). Occurrence, distribution and seasonal variation of antibiotics in the Huangpu River, Shanghai, China. Chemosphere, 82(6), 822–828.CrossRefGoogle Scholar
  21. Jiang, L., Hu, X., Xu, T., Zhang, H., Sheng, D., & Yin, D. (2013). Prevalence of antibiotic resistance genes and their relationship with antibiotics in the Huangpu River and the drinking water sources, Shanghai, China. Science of the Total Environment, 458–460, 267–272.CrossRefGoogle Scholar
  22. Knapp, C. W., Cardoza, L. A., Hawes, J. N., Wellington, E. M., Larive, C. K., & Graham, D. W. (2005). Fate and effects of enrofloxacin in aquatic systems under different light conditions. Environmental Science and Technology, 39(23), 9140–9146.CrossRefGoogle Scholar
  23. Kolpin, D. W., Furlong, E. T., Meyer, M. T., Thurman, E. M., Zaugg, S. D., Barber, L. B., et al. (2002). Pharmaceuticals, hormones, and other organic wastewater contaminants in U.S. streams, 1999–2000: a national reconnaissance. Environmental Science and Technology, 36(6), 1202–1211.CrossRefGoogle Scholar
  24. Kumar, K., Gupta, S. C., Baidoo, S. K., Chander, Y., & Rosen, C. J. (2005). Antibiotic uptake by plants from soil fertilized with animal manure. Journal of Environmental Quality, 34(6), 2082–2085.CrossRefGoogle Scholar
  25. Kummerer, K. (2009). Antibiotics in the aquatic environment—a review—part II. Chemosphere, 75(4), 417–434.CrossRefGoogle Scholar
  26. Le Corre, K. S., Ort, C., Kateley, D., Allen, B., Escher, B. I., & Keller, J. (2012). Consumption-based approach for assessing the contribution of hospitals towards the load of pharmaceutical residues in municipal wastewater. Environment International, 45, 99–111.CrossRefGoogle Scholar
  27. Leung, H. W., Minh, T. B., Murphy, M. B., Lam, J. C., So, M. K., Martin, M., et al. (2012). Distribution, fate and risk assessment of antibiotics in sewage treatment plants in Hong Kong, South China. Environment International, 42, 1–9.CrossRefGoogle Scholar
  28. Leung, H. W., Jin, L., Wei, S., Tsui, M. M., Zhou, B., Jiao, L., et al. (2013). Pharmaceuticals in tap water: human health risk assessment and proposed monitoring framework in China. Environmental Health Perspectives, 121(7), 839–846.CrossRefGoogle Scholar
  29. Li, B., Zhang, T., Xu, Z., & Fang, H. H. (2009). Rapid analysis of 21 antibiotics of multiple classes in municipal wastewater using ultra performance liquid chromatography-tandem mass spectrometry. Analytica Chimica Acta, 645(1-2), 64–72.CrossRefGoogle Scholar
  30. Li, W., Shi, Y., Gao, L., Liu, J., & Cai, Y. (2012). Occurrence of antibiotics in water, sediments, aquatic plants, and animals from Baiyangdian Lake in North China. Chemosphere, 89, 1307–1315.CrossRefGoogle Scholar
  31. Li, W., Shi, Y., Gao, L., Liu, J., & Cai, Y. (2013). Occurrence, distribution and potential affecting factors of antibiotics in sewage sludge of wastewater treatment plants in China. Science of the Total Environment, 445–446, 306–313.CrossRefGoogle Scholar
  32. Li, N., Zhang, X., Wu, W., & Zhao, X. (2014). Occurrence, seasonal variation and risk assessment of antibiotics in the reservoirs in North China. Chemosphere, 111, 327–335.CrossRefGoogle Scholar
  33. Liang, X., Chen, B., Nie, X., Shi, Z., Huang, X., & Li, X. (2013). The distribution and partitioning of common antibiotics in water and sediment of the Pearl River Estuary, South China. Chemosphere, 92(11), 1410–1416.CrossRefGoogle Scholar
  34. Liu, J. L., & Wong, M. H. (2013). Pharmaceuticals and personal care products (PPCPs): a review on environmental contamination in China. Environment International, 59, 208–224.CrossRefGoogle Scholar
  35. Lubick, N. (2010). Drugs in the environment: do pharmaceutical take-back programs make a difference? Environmental Health Perspectives, 118(5), A210–A214.CrossRefGoogle Scholar
  36. Manzetti, S., & Ghisi, R. (2014). The environmental release and fate of antibiotics. Marine Pollution Bulletin, 79(1-2), 7–15.CrossRefGoogle Scholar
  37. Medhi, B., & Sewal, R. K. (2012). Ecopharmacovigilance: an issue urgently to be addressed. Indian Journal of Pharmacology, 44(5), 547–549.CrossRefGoogle Scholar
  38. Minh, T. B., Leung, H. W., Loi, I. H., Chan, W. H., So, M. K., Mao, J. Q., et al. (2009). Antibiotics in the Hong Kong metropolitan area: Ubiquitous distribution and fate in Victoria Harbour. Marine Pollution Bulletin, 58(7), 1052–1062.CrossRefGoogle Scholar
  39. Mohring, S. A., Strzysch, I., Fernandes, M. R., Kiffmeyer, T. K., Tuerk, J., & Hamscher, G. (2009). Degradation and elimination of various sulfonamides during anaerobic fermentation: a promising step on the way to sustainable pharmacy? Environmental Science and Technology, 43(7), 2569–2574.CrossRefGoogle Scholar
  40. 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. Marine Pollution Bulletin, 69(1-2), 233–237.CrossRefGoogle Scholar
  41. Na, G., Zhang, W., Zhou, S., Gao, H., Lu, Z., Wu, X., et al. (2014). Sulfonamide antibiotics in the Northern Yellow Sea are related to resistant bacteria: Implications for antibiotic resistance genes. Marine Pollution Bulletin, 84(1-2), 70–75.CrossRefGoogle Scholar
  42. Pruden, A., Larsson, D. G., Amézquita, A., Collignon, P., Brandt, K. K., Graham, D. W., et al. (2013). Management options for reducing the release of antibiotics and antibiotic resistance genes to the environment. Environmental Health Perspectives, 121(8), 878–885.CrossRefGoogle Scholar
  43. Rastogi, T., Leder, C., & Kümmerer, K. (2014). Designing green derivatives of β-blocker Metoprolol: a tiered approach for green and sustainable pharmacy and chemistry. Chemosphere, 111, 493–499.CrossRefGoogle Scholar
  44. Rodriguez-Mozaz, S., & Weinberg, H. S. (2010). Meeting report: pharmaceuticals in water-an interdisciplinary approach to a public health challenge. Environmental Health Perspectives, 118(7), 1016–1020.CrossRefGoogle Scholar
  45. Santos, L. H., Gros, M., Rodriguez-Mozaz, S., Delerue-Matos, C., Pena, A., Barceló, D., et al. (2013). Contribution of hospital effluents to the load of pharmaceuticals in urban wastewaters: identification of ecologically relevant pharmaceuticals. Science of the Total Environment, 461–462, 302–316.CrossRefGoogle Scholar
  46. Segura, P. A., François, M., Gagnon, C., & Sauvé, S. (2009). Review of the occurrence of anti-infectives in contaminated wastewaters and natural and drinking waters. Environmental Health Perspectives, 117(5), 675–684.CrossRefGoogle Scholar
  47. Shi, H., Yang, Y., Liu, M., Yan, C., Yue, H., & Zhou, J. (2014). Occurrence and distribution of antibiotics in the surface sediments of the Yangtze Estuary and nearby coastal areas. Marine Pollution Bulletin, 83(1), 317–323.CrossRefGoogle Scholar
  48. Stackelberg, P. E., Furlong, E. T., Meyer, M. T., Zaugg, S. D., Henderson, A. K., & Reissman, D. B. (2004). Persistence of pharmaceutical compounds and other organic wastewater contaminants in a conventional drinking-water-treatment plant. Science of the Total Environment, 329(1-3), 99–113.CrossRefGoogle Scholar
  49. Straub, J. O. (2002). Environmental risk assessment for new human pharmaceuticals in the European Union according to the draft guideline/discussion paper of January 2001. Toxicology Letters, 135(3), 231–237.CrossRefGoogle Scholar
  50. Sui, Q., Wang, B., Zhao, W., Huang, J., Yu, G., Deng, S., et al. (2012). Identification of priority pharmaceuticals in the water environment of China. Chemosphere, 89, 280–286.CrossRefGoogle Scholar
  51. Sumpter, J. P., & Roig, B. (2012). Ecological and human health risk assessments of antibiotics and anti-cancer drugs found in the environment. Available from URL: Accessed May 2012.
  52. Suzuki, S., & Hoa, P. T. (2012). Distribution of quinolones, sulfonamides, tetracyclines in aquatic environment and antibiotic resistance in Indochina. Frontiers in Microbiology, 3, 67.Google Scholar
  53. Tao, R., Ying, G. G., Su, H. C., Zhou, H. W., & Sidhu, J. P. (2010). Detection of antibiotic resistance and tetracycline resistance genes in Enterobacteriaceae isolated from the Pearl rivers in South China. Environmental Pollution, 158(6), 2101–2109.CrossRefGoogle Scholar
  54. Tong, C., Zhuo, X., & Guo, Y. (2011). Occurrence and risk assessment of four typical fluoroquinolone antibiotics in raw and treated sewage and in receiving waters in Hangzhou, China. Journal of Agricultural and Food Chemistry, 59(13), 7303–7309.CrossRefGoogle Scholar
  55. 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. The Lancet Infectious Diseases, 14(8), 742–750.CrossRefGoogle Scholar
  56. Verlicchi, P., Al Aukidy, M., & Zambello, E. (2012a). Occurrence of pharmaceutical compounds in urban wastewater: removal, mass load and environmental risk after a secondary treatment—a review. Science of the Total Environment, 429, 123–155.CrossRefGoogle Scholar
  57. Verlicchi, P., Al Aukidy, M., Galletti, A., Petrovic, M., & Barceló, D. (2012b). Hospital effluent: investigation of the concentrations and distribution of pharmaceuticals and environmental risk assessment. Science of the Total Environment, 430, 109–118.CrossRefGoogle Scholar
  58. Wang, J., & Hu, X. (2014). Ecopharmacovigilance: current state, challenges, and opportunities in China. Indian Journal of Pharmacology, 46(1), 13–17.CrossRefGoogle Scholar
  59. Watkinson, A. J., Murky, E. J., Colin, D. W., & Costanzia, S. D. (2009). The occurrence of antibiotics in an urban watershed: from wastewater to drinking water. Science of the Total Environment, 1, 2711–2723.CrossRefGoogle Scholar
  60. Wellington, E. M., Boxall, A. B., Cross, P., Feil, E. J., Gaze, W. H., Hawkey, P. M., et al. (2013). The role of the natural environment in the emergence of antibiotic resistance in Gram-negative bacteria. The Lancet Infectious Diseases, 13(2), 155–165.CrossRefGoogle Scholar
  61. World Health Organization. (2012). The evolving threat of antimicrobial resistance: options for action. Geneva: World Health Organization.Google Scholar
  62. Wu, C., Huang, X., Witter, J. D., Spongberg, A. L., Wang, K., Wang, D., et al. (2014). Occurrence of pharmaceuticals and personal care products and associated environmental risks in the central and lower Yangtze river, China. Ecotoxicology and Environmental Safety, 106, 19–26.CrossRefGoogle Scholar
  63. 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 effluent-receiving river. Chemosphere, 119, 1379–1385.CrossRefGoogle Scholar
  64. Yan, C., Yang, Y., Zhou, J., Liu, M., Nie, M., Shi, H., et al. (2013). Antibiotics in the surface water of the Yangtze Estuary: occurrence, distribution and risk assessment. Environmental Pollution, 175, 22–29.CrossRefGoogle Scholar
  65. Yan, Q., Gao, X., Huang, L., Gan, X. M., Zhang, Y. X., Chen, Y. P., et al. (2014). Occurrence and fate of pharmaceutically active compounds in the largest municipal wastewater treatment plant in Southwest China: mass balance analysis and consumption back-calculated model. Chemosphere, 99, 160–170.CrossRefGoogle Scholar
  66. Yang, J. F., Ying, G. G., Zhao, J. L., Tao, R., Su, H. C., & Chen, F. (2010). Simultaneous determination of four classes of antibiotics in sediments of the Pearl Rivers using RRLC-MS/MS. Science of the Total Environment, 408, 3424–3432.CrossRefGoogle Scholar
  67. Yang, Y., Zhang, T., Zhang, X. X., Liang, D. W., Zhang, M., Gao, D. W., et al. (2012). Quantification and characterization of β-lactam resistance genes in 15 sewage treatment plants from East Asia and North America. Applied Microbiology and Biotechnology, 95(5), 1351–1358.CrossRefGoogle Scholar
  68. Yin, X., Song, F., Gong, Y., Tu, X., Wang, Y., Cao, S., et al. (2013). A systematic review of antibiotic utilization in China. Journal of Antimicrobial Chemotherapy, 68(11), 2445–2452.CrossRefGoogle Scholar
  69. Yiruhan, Wang, Q. J., Mo, C. H., Li, Y. W., Gao, P., Tai, Y. P., et al. (2010). Determination of four fluoroquinolone antibiotics in tap water in Guangzhou and Macao. Environmental Pollution, 158(7), 2350–2358.CrossRefGoogle Scholar
  70. Yu, X., Zuo, J., Li, R., Gan, L., Li, Z., & Zhang, F. (2014). A combined evaluation of the characteristics and acute toxicity of antibiotic wastewater. Ecotoxicology and Environmental Safety, 106, 40–45.CrossRefGoogle Scholar
  71. Zhang, R., Eggleston, K., Rotimi, V., & Zeckhauser, R. J. (2006). Antibiotic resistance as a global threat: evidence from China, Kuwait and the United States. Global Health, 2, 6.CrossRefGoogle Scholar
  72. Zhang, X., Zhang, D., Zhang, H., Luo, Z., & Yan, C. (2012). Occurrence, distribution, and seasonal variation of estrogenic compounds and antibiotic residues in Jiulongjiang River, South China. Environmental Science and Pollution Research, 19(5), 1392–1404.CrossRefGoogle Scholar
  73. Zhang, H., Liu, P., Feng, Y., & Yang, F. (2013a). Fate of antibiotics during wastewater treatment and antibiotic distribution in the effluent-receiving waters of the Yellow Sea, northern China. Marine Pollution Bulletin, 73(1), 282–290.CrossRefGoogle Scholar
  74. Zhang, R., Tang, J., Li, J., Zheng, Q., Liu, D., Chen, Y., et al. (2013b). Antibiotics in the offshore waters of the Bohai Sea and the Yellow Sea in China: occurrence, distribution and ecological risks. Environmental Pollution, 174, 71–77.CrossRefGoogle Scholar
  75. Zhang, R., Tang, J., Li, J., Cheng, Z., Chaemfa, C., Liu, D., et al. (2013c). Occurrence and risks of antibiotics in the coastal aquatic environment of the Yellow Sea, North China. Science of the Total Environment, 450–451, 197–204.CrossRefGoogle Scholar
  76. Zheng, Q., Zhang, R., Wang, Y., Pan, X., Tang, J., & Zhang, G. (2012). Occurrence and distribution of antibiotics in the Beibu Gulf, China: impacts of river discharge and aquaculture activities. Marine Environmental Research, 78, 26–33.CrossRefGoogle Scholar
  77. Zhou, L. J., Ying, G. G., Zhao, J. L., Yang, J. F., Wang, L., Yang, B., et al. (2011). Trends in the occurrence of human and veterinary antibiotics in the sediments of the Yellow River, Hai River and Liao River in northern China. Environmental Pollution, 159(7), 1877–1885.CrossRefGoogle Scholar
  78. Zhou, L. J., Ying, G. G., Liu, S., Zhao, J. L., Yang, B., Chen, Z. F., et al. (2013). Occurrence and fate of eleven classes of antibiotics in two typical wastewater treatment plants in South China. Science of the Total Environment, 452–453, 365–376.CrossRefGoogle Scholar
  79. Zou, S., Xu, W., Zhang, R., Tang, J., Chen, Y., & Zhang, G. (2011). Occurrence and distribution of antibiotics in coastal water of the Bohai Bay, China: impacts of river discharge and aquaculture activities. Environmental Pollution, 159(10), 2913–2920.CrossRefGoogle Scholar
  80. Zou, X. X., Fang, Z., Min, R., Bai, X., Zhang, Y., Xu, D., et al. (2014). Is nationwide special campaign on antibiotic stewardship program effective on ameliorating irrational antibiotic use in China? Study on the antibiotic use of specialized hospitals in China in 2011–2012. Journal of Huazhong University of Science and Technology(Medical Sciences), 34(3), 456–463.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Hubei Woman and Child HospitalWuhanChina
  2. 2.Department of Pharmacy, College of MedicineWuhan University of Science and TechnologyWuhanChina

Personalised recommendations