Institute of Environmental Medicine and Hospital Epidemiology, Freiburg University Hospital, Hugstetter Straße 55, D-79106 Freiburg, Germany
Keywords: antibiotics, environment
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Background |
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The selection and development of antibiotic-resistant bacteria is one of the greatest concerns with regard to the use of antimicrobials.25 In a report by the House of Lords, it is stated that: resistance to antibiotics and other anti-infective agents constitutes a major threat to public health and ought to be recognized as such more widely than it is at present.4 Therefore, the European Union (EU) recommends the prudent use of antimicrobial agents in human medicine.2 With respect to the causes of resistance, the focus is on the use of antimicrobials in hospitals, by medical practitioners, i.e. in prescriptions2 and in animal husbandry. ...Coordination between human, veterinary and environment sectors should be ensured and the magnitude of the relationship between the occurrence of antimicrobial resistant pathogens in humans, animals and the environment should be further clarified....2 However, very little is known about their contribution to the level of bacterial resistance in the environment and its significance. Also, surprisingly, little is known about the extent of environmental occurrence, transport, and ultimate fate and effects of pharmaceuticals in general, as well as of antibiotics in particular.1
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Use of antibiotics and input into the environment |
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Wise estimated total antibiotic market consumption world-wide to lie between 100 000 and 200 000 tons.9
Unused therapeutic drugs are sometimes disposed of into the sewage system. If the drugs are not degraded or eliminated during sewage treatment, in soil or in other environmental compartments, they will reach surface water and ground water, and, potentially, drinking water. Unmetabolized antibiotic substances are often passed into the aquatic environment in wastewater. Antibiotics used for veterinary purposes or as growth promoters are excreted by the animals and end up in manure. Manure is used as an agricultural fertilizer; thus, the antibiotics seep through the soil and enter ground water (Figure 1). However, very little is known about the occurrence, fate and risks associated with antibiotics entering the environment after being used in human and veterinary medicine and as growth promoters; 95% community use is reported for the UK.4 The figure for the USA is 75%.9 In Germany, 75% of antimicrobials are used in the community and 25% in hospitals.
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Fate in the environment |
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Effects |
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Concentrations below therapeutic levels may play a role in the selection of resistance and its genetic transfer in certain bacteria. Exposure of bacteria to sub-therapeutic antimicrobial concentrations is thought to increase the speed at which resistant strains of bacteria are selected. Resistance can be transferred to other bacteria living in other environments such as ground water or drinking water. In general, knowledge of subinhibitory concentrations and their effects against environmental bacteria is poor, especially with respect to resistance. There are a number of recent and older publications about the mechanisms of very low antibiotic concentrations on the expression of bacterial virulence factors. As for the fate and effects of antibiotics against bacteria and other organisms in the environment, it is not clear whether the standardized tests used for risk assessment of chemicals are appropriate for antibiotics and other pharmaceuticals. Studies using test systems indicate that various antibiotics remain active against different groups of bacteria present in waste water.11,12 Effects against algae and daphnids have been reported at surprisingly low concentrations (5100 µg/L).2628
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Risk: assessment and management |
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The emission of antibiotics into the environment should be reduced as an important part of the risk management. For this reason, unused therapeutic drugs should not be flushed down the drain and physicians must be made aware that antibiotics are not completely metabolized by patients. On the contrary, antibiotics and other pharmaceuticals are often excreted largely unchanged, i.e. as active compounds. Doctors and patients as well as pharmacists play an important role in reducing the release of antibiotics, other pharmaceuticals, and disinfectants into the environment. The environmental significance of therapeutic drugs, disinfectants and diagnostics should be included in the undergraduate curricula of medical students and pharmacists. Patients should be made aware that antibiotics help against bacterial diseases but not against the common cold, which is caused by viruses. These issues should be addressed as part of a sustainable development in medicine and for the environment. This holds also for the agricultural use of antibiotics as well as their use in fish farming and elsewhere, e.g. as pesticides or for pets.
Because of the timescales involved in acquiring the necessary knowledge, in the reaction times of ecological systems,29 in getting people to react, and also the socio-economic timescales involved we have to act nowat least for precautionary reasons and sustainable development. This is especially important in respect of the effects of antibiotics, i.e. the promotion of resistance.
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Conclusions |
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Footnotes |
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References |
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2 . The Council of the European Union. (2002). Council Recommendation of 15 November 2001 on the Prudent Use of Antimicrobial Agents in Human Medicine (Text with EEA relevance). 2002/77/EC. 5 February, Brussels, Belgium.
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Wise, R., Hart, T., Cars, O. et al. (1998). Antimicrobial resistance is a major threat to public health. British Medical Journal 317, 60910.
4 . House of Lords Select Committee on Science and Technology. (1998). 7th Report. The Stationery Office, London, UK.
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7 . European Federation of Animal Health (FEDESA). (2001). Antibiotic Use in Farm Animals does not threaten Human Health. FEDESA/FEFANA Press release. 13 July. Brussels, Belgium.
8 . Union of Concerned Scientists. (2001). 70 Percent of All Antibiotics Given to Healthy Livestock. Press release. 8 January. Cambridge, MA, USA.
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Wise, R. (2002). Antimicrobial resistance: priorities for action. Journal of Antimicrobial Chemotherapy 49, 5856.
10 . Hartmann, A., Golet, E. M., Gartiser, S. et al. (1999). Primary DNA damage but not mutagenicity correlates with ciprofloxacin concentrations in German hospital waste waters. Archives of Environmental Contamination and Toxicology 36, 1159.[CrossRef][ISI][Medline]
11 . Kümmerer, K. (2001). Drugs in the environment: emission of drugs, diagnostic aids and disinfectants into wastewater by hospitals in relation to other sourcesa review. Chemosphere 45, 95769.[CrossRef][ISI][Medline]
12 . Kümmerer, K. & Henninger, A. (2003). Promoting resistance by the emission of antibiotics from hospitals and households into effluents. Clinical Microbiology and Infection, in press.
13 . Zuccato, E., Calamari, D., Natangelo, M. et al. (2000). Presence of therapeutic drugs in the environment. Lancet 335, 178990.
14 . Golet, E. M., Alder, A. C., Hartmann, A. et al. (2001). Trace determination of fluoroquinolone antibacterial agents in urban wastewater by solid-phase extraction and liquid chromatography with fluorescence detection. Analytical Chemistry 73, 36328.[CrossRef][ISI][Medline]
15 . Sacher, F., Brauch, H.-J., Lange, F. T. et al. (2001). Occurrence of antibiotics in groundwater in Baden-Württemberg, Germanyresults of a comprehensive monitoring program. In Abstracts of the 11th Annual Meeting of SETAC Europe (Society of Environmental Toxicology and Chemistry), Madrid, Spain, 2001. Abstract M/EH056, p. 112. SETAC Europe, Brussels, Belgium.
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17 . Hamscher, G., Sczesny, S., Höper, H. et al. (2002). Determination of persistent tetracycline residues in soil fertilized with liquid manure by high-performance liquid chromatography with electrospray ionization tandem mass spectrometry. Analytical Chemistry 74, 150918.[CrossRef][ISI][Medline]
18 . Kümmerer, K., Al-Ahmad, A. & Mersch-Sundermann, V. (2000). Biodegradability of some antibiotics, elimination of the genotoxicity and affection of wastewater bacteria in a simple test. Chemosphere 40, 70110.[CrossRef][ISI][Medline]
19 . Al-Ahmad, A., Daschner, F. D. & Kümmerer, K. (1999). Biodegradability of cefotiam, ciprofloxacin, meropenem, penicillin G, and sulfamethoxazole and inhibition of waste water bacteria. Archives of Environmental Contamination and Toxicology 37, 15863.[CrossRef][ISI][Medline]
20 . Marengo, J. R., Kok, R. A., Velagaleti, R. et al. (1997). Aerobic degradation of 14C-sarafloxacin hydrochloride in soil. Environmental Toxicology and Chemistry 16, 46271.[ISI]
21 . Weerasinghe, C. A. & Towner, D. (1997). Aerobic biodegradation of virginiamycin in soil. Environmental Toxicology and Chemistry 16, 18736.[ISI]
22 . Nygaard, K., Lunestad, B. T., Hektoern, H. et al. (1992). Resistance to oxytetracycline, oxolinic acid and furazolidone in bacteria from marine sediments. Aquaculture 104, 2136.
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Guardabassi, L., Petersen, A., Olsen, J. E. et al. (1998). Antibiotic resistance in Acinetobacter spp. isolated from sewers receiving waste effluent from a hospital and a pharmaceutical plant. Applied and Environmental Microbiology 64, 3499502.
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Witte, W. (1998). Medical consequences of antibiotic use in agriculture. Science 279, 9967.
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26 . Holten-Lützhøft, H.-C., Halling-Sørensen, B. & Jörgensen, S. E. (1999). Algae toxicity of antibacterial agents applied in Danish fish farming. Archives of Environmental Contamination and Toxicology 36, 16.[CrossRef][ISI][Medline]
27 . Wollenberger, L., Halling-Sørensen, B. & Kusk, K. O. (2000). Acute and chronic toxicity of veterinary antibiotics to Daphnia magna. Chemosphere 40, 72330.[CrossRef][ISI][Medline]
28 . Macri, A., Stazi, V. & Dojmi di Delupis, G. (1988). Acute toxicity of furazolidone on Artemia salina, Daphnia magna, and Culex pipiens molestus larvae. Ecotoxicology and Environmental Safety 16, 904.[ISI][Medline]
29 . Kümmerer, K. (1996). The ecological impact of time. Time and Society 5, 21925.