Abstract
Fluoroquinolones are a valuable synthetic antibacterial class widely used in the treatment of infectious diseases both in humans and animals. Until recently, it has been thought that bacterial resistance to fluoroquinolones develops very slowly. Nowadays, there are multiple studies that reveal the alarming occurrence of bacterial resistance and there is a high risk of becoming therapeutically useless. The emergence of this phenomenon comes from injudicious usage in therapy, the presence of residues and their metabolites in food of animal origin and also in sewage, compost and domestic waste, which end up in soil and water sources. In the present paper, we reviewed important issues regarding fluoroquinolones impact on the environment in connection with the development of bacterial resistance: (1) the presence of fluoroquinolones as pollutants in soil, surface waters, and food. Fluoroquinolones are persistent with high specificity to interact with soil compared to other antibiotics. Pollution of water sources raises concerns regarding the effects of small concentrations (ng L−1) on human health and also of the environment. The non-therapeutic use in animal farms conducts to food pollution; the cultivated plants could concentrate the fluoroquinolones (over 100 μg L−1); (2) the increase of bacterial resistance to fluoroquinolones occurring with specific mutations in the target enzymes as well by the plasmid-mediated resistance and active efflux of the cell; (3) international regulations of the fluoroquinolone residues in food that are far to encompass all compounds; (4) fluoroquinolones residues analysis with standardized methods should provide limits of detection lower than maximum residue limit values; and (5) trends and perspectives: (a) a wider process of harmonization of regulations; (b) the fluoroquinolones restriction, necessary for low levels of bacterial resistance; (c) the soil and waste water purification methods; (d) the practice of soil planting scheme as an alternative; and (e) an environmental label in order to facilitate the selection of drugs.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Adachi F, Yamamoto A, Takakura K, Kawahara R (2013) Occurrence of fluoroquinolones and fluoroquinolone-resistance genes in the aquatic environment. Sci Total Environ 444:508–514. doi:10.1016/j.scitotenv.2012.11.077
Albini A, Monti S (2003) Photophysics and photochemistry of fluoroquinolones. Chem Soc Rev 32:238–250. doi:10.1039/B209220B
Aldred KJ, Kerns RJ, Osheroff N (2014) Mechanism of quinolone action and resistance. Biochemistry 53:1565–1574. doi:10.1021/bi5000564
ALINORM 10/33/42 (2009) Report of the third session of the Codex ad hoc Intergovernmental Task Force on Antimicrobial Resistance, Jeju, Republic of Korea, 12–16 October 2009. Rome, Available via FDA Codex Alimentarius Commission. www.codexalimentarius.net/input/download/report/730/al33_42e.pdf. Accessed 01 Aug 2014
Anand N, Remers WA (2003) Synthetic antibacterial agents. In: Abraham DJ (ed) Burger's medicinal chemistry and drug discovery, volume 5 Chemotherapeutic Agents, 6th edn. Wiley, New York, pp 582–594
Andreu V, Blasco C, Pico Y (2007) Analytical strategies to determine quinolone residues in food and the environment. TrAC-Trend Anal Chem 26:534–556. doi:10.1016/j.trac.2007.01.010
Aypak C, Altunsoy A, Düzgün N (2009) Empiric antibiotic therapy in acute uncomplicated urinary tract infections and fluoroquinolone resistance: a prospective observational study. Ann Clin Microbiol Antimicrob 8:27. doi:10.1186/1476-0711-8-27
Ball P (2000) Quinolone generations: natural history or natural selection? J Antimicrob Chemother 46:17–24
Baquero F, Martínez JL, Cantón R (2008) Antibiotics and antibiotic resistance in water environments. Curr Opin Biotechnol 19:260–265. doi:10.1016/j.copbio.2008.05.006
Beale JM Jr (2011) Chapter 6 Anti-infective agents. In: Block JH, Beale JM (eds) Wilson and Gisvold’s textbook of organic medicinal and pharmaceutical chemistry, 12th edn. Lippincott Williams and Wilkins, Philadelphia, pp 206–213
Blasco C, Torres CM, Pico Y (2007) Progress in analysis of residual antibacterials in food. TrAC-Trend Anal Chem 26:895–912. doi:10.1016/j.trac.2007.08.001
Bolon MK (2011) The newer fluoroquinolones. Med Clin N Am 95:793–817. doi:10.1016/j.mcna.2011.03.006
Brain RA, Hanson ML, Solomon KR, Brooks BW (2008) Aquatic plants exposed to pharmaceuticals: effects and risks. Rev Environ Contam Toxicol 192:67–115. doi:10.1007/978-0-387-71724-1_3
CAC/GL 71-2009 guidelines for the design and implementation of national regulatory food safety assurance programmes associated with the use of veterinary drugs in food producing animals. Available via CODEX ALIMENTARIUS. http://www.codexalimentarius.org/standards/list-of-standards/en/?provide=standards&orderField=fullReference&sort=asc. Accessed 01 Aug 2014
CAC/MRL 2-2012 Maximum residue limits for veterinary drugs in foods. Available via CODEX ALIMENTARIUS. http://www.codexalimentarius.org/standards/list-of-standards/en/?provide=standards&orderField=fullReference&sort=asc. Accessed 01 Aug 2014
Carlet J, Jarlier V, Harbarth S, Voss A, Goossens H, Pittet D (2012) Ready for a world without antibiotics? The pensières antibiotic resistance call to action. Antimicrob Resist Infect Control 1:11. doi:10.1186/2047-2994-1-11
Cheng AC, Turnidge J, Collignon P, Looke D, Barton M, Gottlieb T (2012) Control of fluoroquinolone resistance through successful regulation, Australia. Emerg Infect Dis 18:1453–1460. doi:10.3201/eid1809.111515
Cheng G, Hao H, Dai M, Liu Z, Yuan Z (2013) Antibacterial action of quinolones: from target to network. Eur J Med Chem 66:555–562. doi:10.1016/j.ejmech.2013.01.057
Collignon P, Powers JH, Chiller TM, Aidara-Kane A, Aarestrup FM (2009) World Health Organization ranking of antimicrobials according to their importance in human medicine: a critical step for developing risk management strategies for the use of antimicrobials in food production animals. Clin Infect Dis 49:132–141. doi:10.1086/599374
COMMISSION DECISION 2002/657/EC (2002) concerning the performance of analytical methods and the interpretation of results, Official Journal of the European Communities, L 221/8-36. Available via Eur-lex. http://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32002D0657&from=EN. Accessed 01 Aug 2014
COUNCIL REGULATION (EEC) No 2377/90 (1990) laying down a Community procedure for the establishment of maximum residue limits of veterinary medicinal products in foodstuffs of animal origin, Off J Eur Union L224:1-8, Available via European Commission. http://ec.europa.eu/health/files/eudralex/vol-5/reg_1990_2377/reg_1990_2377_en.pdf. Accessed 01 Aug 2014
Crespo-Alonso M, Nurchi VM, Biesuz R, Alberti G, Spano N, Pilo MI, Sanna G (2013) Biomass against emerging pollution in wastewater: ability of cork for the removal of ofloxacin from aqueous solutions at different pH. J Environ Chem Eng 1:1199–1204. doi:10.1016/j.jece.2013.09.010
CVM GFI#209 (2012) The judicious use of medically important antimicrobial drugs in food-producing animals. Available via FDA http://www.fda.gov/downloads/animalveterinary/guidancecomplianceenforcement/guidanceforindustry/ucm216936.pdf. Accessed 01 Aug 2014
CVM GFI #3 Guidance For Industry. Guidance No. 3 (2006) General principles for evaluating the safety of compounds used in food-producing animals. Available via FDA. http://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/UCM052180.pdf. Accessed 01 Aug 2014
EMA/CVMP/479774/2010, EMEA/V/C/159 (2010) Veraflox/Pradofloxacin. Available via EMA http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/veterinary/000159/WC500109015.pdf. Accessed 01 Aug 2014
EMEA/576176/2009, ECDC/EMEA Joint Technical Report (2009) The bacterial challenge: time to react, Stockholm. doi 10.2900/2518. Available via EMA http://www.ecdc.europa.eu/en/publications/Publications/0909_TER_The_Bacterial_Challenge_Time_to_React.pdf Accessed 01 Aug 2014
EMEA/CVMP/416168/2006-FINAL (2006) Reflection paper on the use of fluoroquinolones in food-producing animals in the european union: development of resistance and impact on human and animal health, Committee for Medicinal Products for Veterinary Use. Available via EMA http://www.ema.europa.eu/docs/en_GB/document_library/Other/2009/10/WC500005173.pdf. Accessed 01 Aug 2014
EMEA/CVMP/SAGAM/184651/2005—CONSULTATION (2006) Reflection paper on the use of fluoroquinolones in food-producing animals in the European Union: development of resistance and impact on human and animal health. Available via EMA http://www.ema.europa.eu/docs/en_GB/document_library/Other/2009/10/WC500005155.pdf. Accessed 01 Aug 2014
Ernervik A (2011) A risk analysis of the potential harm on the soil environment caused by antibiotics in biosolids. Lund University, Bachelor Degree
FDA Veterinarian Newsletter FDA Veterinarian Newsletter, July/August 2001 Volume XVI, No IV—Approval Withdrawn for Abbott Laboratories’ Poultry Fluoroquinolone Drugs. Available via FDA http://www.fda.gov/AnimalVeterinary/NewsEvents/FDAVeterinarianNewsletter/ucm130729.htm. Accessed 01 Aug 2014
Fernández F, Pinacho DG, Gratacós-Cubarsí M, García-Regueiro JA, Castellari M, Sánchez-Baeza F, Marco MP (2014) Immunochemical determination of fluoroquinolone antibiotics in cattle hair: a strategy to ensure food safety. Food Chem 157:221–228. doi:10.1016/j.foodchem.2014.01
Ferrero L, Cameron B, Crouzet J (1995) Analysis of gyrA and grlA mutations in stepwise-selected ciprofloxacin-resistant mutants of Staphylococcus aureus. Antimicrob Agents Chemother 39:1554–1558. doi:10.1128/AAC.39.7.1554
Frade VMF, Dias M, Teixeira ACSC, Palma MSA (2014) Environmental contamination by fluoroquinolones. Braz J Pharm Sci. http://dx.doi.org/10.1590/S1984-82502011000100004
Fukuda H, Hiramatsu K (1999) Primary targets of fluoroquinolones in Streptococcus pneumoniae. Antimicrob Agents Chemother 43:410–412
García-Campaña AM, Gámiz-Gracia L, Lara FJ, del Olmo Iruela M, Cruces-Blanco C (2009) Applications of capillary electrophoresis to the determination of antibiotics in food and environmental samples. Anal Bioanal Chem 395:967–986. doi:10.1007/s00216-009-2867-9
Gobel A, Thomsen A, McArdell CS, Joss A, Giger W (2005) Occurrence and sorption behavior of sulfonamides, macrolides, and trimethoprim in activated sludge treatment. Environ Sci Technol 39:3981–3989. doi:10.1021/es048550a
Golet EM, Xifra I, Siegrist H, Alder AC, Giger W (2003) Environmental exposure assessment of fluoroquinolone antibacterial agents from sewage to soil. Environ Sci Technol 37:3243–3249. doi:10.1021/es0264448
González-Candelas F, Comas I, Martínez JL, Galán JC, Baquero F (2011) 12—the evolution of antibiotic resistance. In: Tibayrenc M (ed) Genetics and evolution of infectious, 1st edn. Elsevier Inc., Burlington, pp 305–337
Jones OA, Voulvoulis N, Lester JN (2001) Human pharmaceuticals in the aquatic environment a review. Environ Technol 22:1383–1394. doi:10.1080/09593332208618186
Kostich MS, Lazorchak JM (2008) Risks to aquatic organisms posed by human pharmaceutical use. Sci Total Environ 389:329–339. doi:10.1016/j.scitotenv.2007.09.008
Kostich MS, Batt AL, Glassmeyer ST, Lazorchak JM (2010) Predicting variability of aquatic concentrations of human pharmaceuticals. Sci Total Environ 408:4504–4510. doi:10.1016/j.scitotenv.2010.06.015
Kostich MS, Batt AL, Lazorchak JM (2014) Concentrations of prioritized pharmaceuticals in effluents from 50 large wastewater treatment plants in the US and implications for risk estimation. Environ Pollut 184:354–359. doi:10.1016/j.envpol.2013.09.013
Kümmerer K (2009) Antibiotics in the aquatic environment—a review—part I. Chemosphere 75:417–434. doi:10.1016/j.chemosphere.2008.11.086
Laponogov I, Pan XS, Veselkov DA, McAuley KE, Fisher LM, Sanderson MR (2010) Structural basis of gate-DNA breakage and resealing by type II topoisomerases. PLoS One. doi:10.1371/journal.pone.0011338
Larsson DG, de Pedro C, Paxeus N (2007) Effluent from drug manufactures contains extremely high levels of pharmaceuticals. J Hazard Mater 148:751–755. doi:10.1016/j.jhazmat.2007.07.008
Leal RM, Figueira RF, Tornisielo VL, Regitano JB (2012) Occurrence and sorption of fluoroquinolones in poultry litters and soils from São Paulo State, Brazil. Sci Total Environ 432:344–349. doi:10.1016/j.scitotenv.2012.06.002
Leal RM, Alleoni LR, Tornisielo VL, Regitano JB (2013) Sorption of fluoroquinolones and sulfonamides in 13 Brazilian soils. Chemosphere 92:979–985. doi:10.1016/j.chemosphere.2013.03.018
Lees P (2013) Pharmacokinetics, pharmacodynamics and therapeutics of pradofloxacin in the dog and cat. J Vet Pharmacol Ther 36:209–221. doi:10.1111/jvp.12036
Lesher GY, Froelich EJ, Gruett MD, Bayley JH, Brundage RP (1962) 1,8 Naphthyridine derivatives, a new class of chemotherapeutic agents. J Med Chem 5:1063–1065. doi:10.1021/jm01240a021
Li JJ (2006) Laughing gas, Viagra, and Lipitor, the human stories behind the drugs we use. Oxford University Press, Oxford
Li D, Yang M, Hu J, Zhang Y, Chang H, Jin F (2008) Determination of penicillin G and its degradation products in a penicillin production wastewater treatment plant and the receiving river. Water Res 42:307–317. doi:10.1016/j.watres.2007.07.016
Li X, Xie Y, Wang J, Christakos G, Si J, Zhao H, Ding Y, Li J (2013) Influence of planting patterns on fluoroquinolone residues in the soil of an intensive vegetable cultivation area in northern China. Sci Total Environ 458–460:63–69. doi:10.1016/j.scitotenv.2013.04.002
Lillenberg M, Yurchenko S, Kipper K et al (2010) Presence of fluoroquinolones and sulfonamides in urban sewage sludge and their degradation as a result of composting. Int J Environ Sci Tech 7:307–312. doi:10.1007/BF03326140
Love DC, Davis MF, Bassett A, Gunther A, Nachman KE (2010) Dose imprecision and resistance: free-choice medicated feeds in industrial food animal production in the United States. Environ Health Perspect 119:279–283. doi:10.1289/ehp.1002625
Lupo A, Coyne S, Berendonk TU (2012) Origin and evolution of antibiotic resistance: the common mechanisms of emergence and spread in water bodies. Front Microbiol 3:18. doi:10.3389/fmicb.2012.00018
Manzetti S, Ghisi R (2014) The environmental release and fate of antibiotics. Mar Pollut Bull 79:7–15. doi:10.1016/j.marpolbul.2014.01.005
Martinez JL (2009) Environmental pollution by antibiotics and by antibiotic resistance determinants. Environ Pollut 157:2893–2902. doi:10.1016/j.envpol.2009.05.051
Martinez M, McDermott P, Walker R (2006) Pharmacology of the fluoroquinolones: a perspective for the use in domestic animals. Vet J 172:10–28. doi:10.1016/j.tvjl.2005.07.010
Mitchell MA (2006) Enrofloxacin. J Exotic Pet Med 15:66–69. doi:10.1053/j.jepm.2005.11.011
Muñoz R, De La Campa AG (1996) ParC subunit of DNA topoisomerase IV of Streptococcus pneumoniae is a primary target of fluoroquinolones and cooperates with DNA gyrase A subunit in forming resistance phenotype. Antimicrob Agents Chemother 40:2252–2257
Näslund J, Hedman JE, Agestrand C (2008) Effects of the antibiotic ciprofloxacin on the bacterial community structure and degradation of pyrene in marine sediment. Aquat Toxicol 90:223–227. doi:10.1016/j.aquatox.2008.09.002
Pallo-Zimmerman L, Byron J, Graves T (2010) Fluoroquinolones: then and now. Compend Contin Educ Vet 32:E1–E9
Pestova E, Millichap JJ, Noskin GA, Peterson LR (2000) Intracellular targets of moxifloxacin: a comparison with other fluoroquinolones. J Antimicrob Chemother 45:583–590. doi:10.1093/jac/45.5.583
Poirel L, Cattoir V, Nordmann P (2008) Is plasmid-mediated quinolone resistance a clinically significant problem? Clin Microbiol Infect 14:295–297. doi:10.1111/j.1469-0691.2007.01930.x
Prabhakaran D, Sukul P, Lamshöft M, Maheswari MA, Zühlke S, Spiteller M (2009) Photolysis of difloxacin and sarafloxacin in aqueous systems. Chemosphere 77:739–746. doi:10.1016/j.chemosphere.2009.08.031
Regitano JB, Leal RMP (2010) Comportamento e impacto de antibióticos usados na produção animal brasileira. Rev Bras Cienc Solo 34:601–616
Rehman MS, Rashid N, Ashfaq M, Saif A, Ahmad N, Han JI (2013) Global risk of pharmaceutical contamination from highly populated developing countries. Chemosphere. doi:10.1016/j.chemosphere.2013.02.036
REP11/AMR (2010) Draft guidelines for risk analysis of foodborne antimicrobial resistance, report of the fourth session of the codex ad hoc intergovernmental task force on antimicrobial resistance. Available via Codex Alimentarius Commission. http://www.who.int/foodborne_disease/resistance/codextf_Oct10/en/. Accessed 01 Aug 2014
Rusu A, Tóth G, Szőcs L, Kökösi J, Kraszni M, Gyéresi Á, Noszál B (2012) Triprotic site-specific acid-base equilibria and related properties of fluoroquinolone antibacterials. J Pharm Biomed Anal 66:50–57. doi:10.1016/j.jpba.2012.02.024
Sárközy G (2001) Quinolones: a class of antimicrobial agents. Vet Med Czech 46:257–274
Sarmah AK, Meyer MT, Boxall ABA (2006) A global perspective on the use, sales, exposure pathways, occurrence, fate and effects of veterinary antibiotics (VAs). Chemosphere 65:725–759. doi:10.1016/j.chemosphere.2006.03.026
Schneider MJ (2009) Methods for the analysis of fluoroquinolones in biological fluids. Bioanalysis 1:415–435. doi:10.4155/bio.09.37
Serrano PH (2005) Responsible use of antibiotics in aquaculture. In: FisheriesTechnical Paper 469, Food and Agriculture Organization of the United Nations (FAO), Rome. Available via FAO. ftp://ftp.fao.org/docrep/fao/009/a0282e/a0282e00.pdf. Accessed 01 Aug 2014
Sharma PC, Jain A, Jain S (2009) Fluoroquinolone antibacterials: a review on chemistry, microbiology and therapeutic prospects. Acta Pol Pharm 66:587–604
Stockholm County Council (2014) Environmentally classified pharmaceuticals. Available via Janusinfo http://www.janusinfo.se/Global/Miljo_och_lakemedel/Miljobroschyr_2014_engelsk_webb.pdf. Accessed 01 Aug 2014
Strahilevitz J, Jacoby GA, Hooper DC, Robicsek A (2009) Plasmid-mediated quinolone resistance: a multifaceted threat. Clin Microbiol Rev 22:664–689. doi:10.1128/CMR.00016-09
Sturini M, Speltini A, Maraschi F et al (2012a) Photodegradation of fluoroquinolones in surface water and antimicrobial activity of the photoproducts. Water Res 46:5575–5582. doi:10.1016/j.watres.2012.07.043(b)
Sturini M, Speltini A, Maraschi F, Profumo A, Pretali L, Fasani E, Albini A (2012b) Sunlight-induced degradation of soil-adsorbed veterinary antimicrobials marbofloxacin and enrofloxacin. Chemosphere 86:130–137. doi:10.1016/j.chemosphere.2011.09.053(a)
Sukul P, Spiteller M (2007) Fluoroquinolones antibiotics in the environment, in reviews of environmental contamination and toxicology. In: Ware GW, Whitacre DM (eds) Reviews of environmental contamination and toxicology 191. Springer, New York, Heidelberg, pp 131–162
Sweetman SC (ed) (2009) Martindale: the complete drug reference, 36th edn. Pharmaceutical Press, London
Ternak G (2005) Antibiotics may act as growth/obesity promoters in humans as an inadvertent result of antibiotic pollution? Med Hypotheses 64:14–16. doi:10.1016/j.mehy.2004.08.003
Webb S, Ternes T, Gibert M, Olejniczak K (2003a) Indirect human exposure to pharmaceuticals via drinking water. Toxicol Lett 42:157–167. doi:10.1016/S0378-4274(03)00071-7
Webb S, Ternes T, Gibert M, Olejniczak K (2003b) Indirect human exposure to pharmaceuticals via drinking water. Toxicol Lett 142:157–167. doi:10.1016/S0378-4274(03)00071-7
Wetzstein HG, Schneider J, Karl W (2010) Comparative biotransformation of fluoroquinolone antibiotics in matrices of agricultural relevance, chapter 6. In: Henderson KL, Coats JR (eds) Veterinary pharmaceuticals in the environment, ACS symposium series 1018. American Chemical Society Books, Washington, pp 67–91
WHO (2011) critically important antimicrobials for human medicine 3rd revision. Available via WHO http://apps.who.int/iris/bitstream/10665/77376/1/9789241504485_eng.pdf. Accessed 01 Aug 2014
Yamane K, Wachino J, Suzuki S et al (2007) New plasmid-mediated fluoroquinolone efflux pump, QepA, found in an Escherichia coli clinical isolate. Antimicrob Agents Chemother 51:3354–3360. doi:10.1128/AAC.00339-07
Zhou LJ, Ying GG, Liu S, Zhang RQ, Lai HJ, Chen ZF, Pan CG (2013) Excretion masses and environmental occurrence of antibiotics in typical swine and dairy cattle farms in China. Sci Total Environ 444:183–195. doi:10.1016/j.scitotenv.2012.11.087
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Rusu, A., Hancu, G. & Uivaroşi, V. Fluoroquinolone pollution of food, water and soil, and bacterial resistance. Environ Chem Lett 13, 21–36 (2015). https://doi.org/10.1007/s10311-014-0481-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10311-014-0481-3