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Journal of Antimicrobial Chemotherapy (2003) 52, 57

DOI: 10.1093/jac/dkg293
Advance Access publication 12 June 2003

Significance of antibiotics in the environment


K. Kmmerer*
Institute of Environmental Medicine and Hospital Epidemiology, Freiburg University Hospital,
Hugstetter Strae 55, D-79106 Freiburg, Germany
Keywords: antibiotics, environment

Pharmaceuticals are designed to stimulate a physiological response


in humans, animals, bacteria or other organisms. During the past
decade, concern has grown about the adverse effects the use and
disposal of pharmaceuticals might potentially have on human and
ecological health. Research has shown that after passing through
wastewater treatment, pharmaceuticals, amongst other compounds,
are released directly into the environment.1
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

Use of antibiotics and input into the environment


In 1996, about 10200 tons of antibiotics were used in the EU, of
which approximately 50% was applied in veterinary medicine and
as growth promoters.6 According to data supplied by the European
Federation of Animal Health (FEDESA),7 in 1999, 13288 tons of
antibiotics were used in the EU and Switzerland, of which 65% was
used in human medicine; 29% was used in the veterinary field and 6%
as growth promoters.7 Since most growth promoters have now been
banned within the EU, only four compounds remain in this group of
feed additives. This may explain the decline in the use of antibiotics
in animal husbandry compared with human medicine. In the USA,

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*Tel: +49-761-270-5464; Fax: +49-761-270-5440; E-mail: k.kuemmerer@iuk3.ukl.uni-freiburg.de


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2003 The British Society for Antimicrobial Chemotherapy

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16 200 tons were produced in 20008 of which 70% was used in livestock farming. This is eight times the amount used in human medicine.
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.
Ciprofloxacin, for example, was found in concentrations of
between 0.7 and 124.5 g/L in hospital effluent.10 Ampicillin was
found in concentrations of between 20 and 80 g/L in the effluent of
a large German hospital.11 Antibiotic concentrations calculated and
measured in hospital effluents are of the same order of magnitude as
the minimum inhibitory concentrations for susceptible pathogenic
bacteria.12 The dilution of hospital effluents by municipal sewage
will lower the concentration of antibiotics only moderately, because
municipal waste water also contains antibiotic substances and disinfectants from households, veterinary sources and to a minor extent
from livestock. Antibiotics have been detected in the g/L range in
municipal sewage, in the effluent of sewage treatment plants (STPs),
in surface water and in ground water.1316 These included quinolones
such as ciprofloxacin, sulphonamides, roxythromycin, dehydrated
erythromycin and others. If antibiotics are used in animal husbandry,
they pass into the soil from manure. Tetracyclines have been detected
in concentrations of up to 0.2 g per kg in soil17 whereas others have
been found in the sediment under fish farms.

Background

Leading article
is used for irrigation, and sewage sludge serves as a fertilizer. This
allows resistant bacteria to enter the food chain directly.
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 g/L).2628

Figure 1. Sources and distribution of pharmaceuticals in the environment1


(STP: sewage treatment plant).

Fate in the environment

Most compounds or at least most groups of compounds acting via the


same mechanisms are found in hospital effluent and in some cases
even in municipal sewage in concentrations that are high enough to
warrant further risk assessment and risk management. It is imperative
that we obtain a better database of the sources, fate and effects of both
antibiotics and resistant bacteria in the environment. This information is necessary if appropriate and, in the long run, successful
measures for sound risk assessment and proper risk management are
to be taken.
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.

Only a few of the compounds were partially biodegraded under test


conditions in aquatic systems.18,19 Most were persistent. The genotoxicity of compounds such as quinolones or metronidazole was not
removed during these tests.18 Quinolones, for example, adsorb
strongly onto sewage sludge, soils and sediments and were not biodegraded in tests with sediments. Less than 1% of sarafloxacin, a fluoroquinolone approved for the prevention of poultry diseases, was
eliminated from different soils within 80 days, probably because of
its high ability to bind to soil.20 Virginiamycin, an antibiotic food
additive administered orally as a growth promoter in farm animals,
was found to biodegrade in different soils, but only with a long halflife.21 Cyclosporin A was shown to degrade only after some months in
samples of wet garden soil, despite the fact that several degrading
strains have been isolated from soil. These findings indicate that biodegradation of antibiotics in STPs and other environmental compartments may not be an option for the reliable removal of antibiotic
substances and this needs more detailed investigation. Furthermore,
future measures aimed at saving water will cause a drop in the volume
of effluent. The consumption of antimicrobials will, however, almost
certainly continue to grow. The resultant higher concentration of
antibiotics in urban waste water will, on the basis of present knowledge, have a substantial impact on bacteria in the aquatic environment.

Effects
Antimicrobials may have qualitative and quantitative effects upon
the resident microbial community of sediments, as summarized by
Nygaard et al.22 Resistant bacteria may be selected by antibiotic
substances in hospital effluent, municipal sewage, aeration tanks, the
anaerobic digestion process of STPs or in soil. Furthermore, resistant
bacteria are excreted and discharged into sewage or soil and other
environmental compartments. Resistant and even multi-resistant
pathogenic bacteria have been detected in wastewater and STPs, as
well as in other environmental compartments.2325 Furthermore, in
arid regions, wastewater containing resistant bacteria and antibiotics

Conclusions
Only little is known about the occurrence, fate, effects and risks
associated with the release of antibiotics and other drugs into the
environment. There is still a lack of fundamental data on the occur-

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Risk: assessment and management

Leading article

References
1. Kmmerer, K. (Ed.). (2001). Pharmaceuticals in the Environment.
Sources, Fate, Effects and Risks. Springer, Heidelberg, Germany.
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.
3. 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.
5. Morris, A. K. & Masterton, R. G. (2002). Antibiotic resistance
surveillance: action for international studies. Journal of Antimicrobial
Chemotherapy 49, 710.
6. European Federation of Animal Health (FEDESA). (1997). Antibiotics and Animals. FEDESA/FEFANA Press release. 8 September.
Brussels, Belgium.
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.
9. 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.
11. Kmmerer, 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.
12. Kmmerer, 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.

Downloaded from http://jac.oxfordjournals.org/ by guest on May 31, 2016

15. Sacher, F., Brauch, H.-J., Lange, F. T. et al. (2001). Occurrence of


antibiotics in groundwater in Baden-Wrttemberg, 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.
16. Kolpin, D., Furlong, E. T., Meyer, M. T. et al. (2002). Pharmaceuticals, hormones, and other organic wastewater contaminants in U.S.
streams, 19992000: a national reconnaissance. Environmental Science
and Technology 36, 120211.
17. Hamscher, G., Sczesny, S., Hper, 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.
18. Kmmerer, 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.
19. Al-Ahmad, A., Daschner, F. D. & Kmmerer, 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.
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.
21. Weerasinghe, C. A. & Towner, D. (1997). Aerobic biodegradation
of virginiamycin in soil. Environmental Toxicology and Chemistry 16,
18736.
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.
23. 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.
24. Witte, W. (1998). Medical consequences of antibiotic use in agriculture. Science 279, 9967.
25. Feuerpfeil, I., Lopez-Pila, J., Schmidt, R. et al. (1999). Antibiotika
resistente Bakterien und Antibiotika in der Umwelt. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 42, 3750.
26. Holten-Ltzhft, H.-C., Halling-Srensen, B. & Jrgensen, S. E.
(1999). Algae toxicity of antibacterial agents applied in Danish fish farming. Archives of Environmental Contamination and Toxicology 36, 16.
27. Wollenberger, L., Halling-Srensen, B. & Kusk, K. O. (2000).
Acute and chronic toxicity of veterinary antibiotics to Daphnia magna.
Chemosphere 40, 72330.
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.
29. Kmmerer, K. (1996). The ecological impact of time. Time and
Society 5, 21925.

rence, fate and effects of antimicrobials in the environment needed


for proper risk assessment and risk management both for humans
and the environment. Hospitals are one, albeit not the only, source of
antibiotic input into the environment. Although antibiotics are used
by patients outside hospitals, in livestock and for pets, attention
should also be paid to their use in hospitals.