Florfenicol in aquaculture: environmental fate of residues and dissemination of antimicrobial resistance genes

Abstract

Florfenicol (FFC) has become a significant antibiotic in the global aquaculture industry, particularly in the treatment of bacterial infections in finfish and shellfish. FFC is valued for its broad-spectrum bacteriostatic activity and effectiveness. This comprehensive review consolidates and expands upon existing research, offering in-depth information on FFC application across various aquaculture practices. This review addresses the key pharmacokinetic aspects of FFC, such as its absorption, distribution, metabolism, and excretion, in aquatic species. Significant attention is given to the safety profile of FFC, with discussions on residue accumulation, elimination dynamics, and the established withdrawal periods necessary to ensure consumer safety. Furthermore, this review highlights emerging issues related to FFC in aquaculture, particularly with respect to plasmid-mediated resistance, the dispersal of resistant bacteria and resistance genes, and their impact on the aquatic environment and nontarget organisms, laying a foundation for future research in this critical area. This evaluative assessment offers a novel contribution to the field, serving as an essential reference for ongoing and future studies on the appropriate use and prevention of FFC resistance in aquatic animal medicine.

Keywords

Amphenicols / Pharmacokinetics / Antibiotic residues / Residue distribution / Resistance genes

References

[1] Akinbowale OL, Peng H, Barton MD. Antimicrobial resistance in bacteria isolated from aquaculture sources in Australia. Journal of Applied Microbiology, 2006, 100(5): 1103-1113

[2] Al-Khalaifah H, Rahman MH, Al-Surrayai T, Al-Dhumair A, Al-Hasan M. A one-health perspective of antimicrobial resistance (AMR): Human, animals and environmental health. Life, 2025, 15: 1598

[3] Allegra S, Loi G, Gamarro EG. Analysis of food safety import notifications and relevant standards and regulations for aquaculture products with a focus on antimicrobial residues and use. Aquaculture Research, 2024, 2024 9427435

[4] Alvarado-Flores C, Encina-Montoya F, Tucca F, Vega-Aguayo R, Nimptsch J, Oberti C, Carmona ER, Lüders C. Assessing the ecological risk of active principles used currently by freshwater fish farms. Science of the Total Environment, 2021, 775 144716

[5] Armstrong, S.M., B.T. Hargrave, and K. Haya. 2005. Antibiotic use in finfish aquaculture: modes of action, environmental fate, and microbial resistance. In Environmental effects of marine finfish aquaculture. Handbook of environmental chemistry, vol 5 M, ed. B.T. Hargrave, 341–357. Berlin, Heidelberg: Springer. https://doi.org/10.1007/b136017

[6] Bardhan A, Abraham TJ. Unraveling the fate of florfenicol and its transformation products in the aquatic ecosystem: A review. Indian Journal of Animal Health, 2023, 62(2): 97-107

[7] Bardhan A, Abraham TJ, Singha J, Saha S, Sarker S, Patil PK. The effects of extended feeding of florfenicol-coated medicated diets on the safety, serum biomarkers and blood cells morphology of Nile tilapia Oreochromis niloticus (L.). Environmental Science and Pollution Research, 2022, 29(26): 39914-39927

[8] Bardhan A, Abraham TJ, Singha J, Sar TK, Rajisha R, Krishna EKN, Kumar KA, Patil PK. Histopathological aberrations and oxidative stress responses in Nile tilapia Oreochromis niloticus as influenced by dietary florfenicol and its metabolites. Aquaculture, 2022, 559 738447

[9] Bardhan A, Abraham TJ, Das R, Patil PK. Biological responses of Nile tilapia Oreochromis niloticus as influenced by dietary florfenicol. Toxics, 2022, 10(10): 571

[10] Bardhan A, Abraham TJ, Singha J, Rajisha R, Krishna EKN, Panda SK, Patil PK. Impacts of oral florfenicol medication and residues on the kidney and liver of Nile tilapia Oreochromis niloticus (L.). Veterinary Sciences, 2023, 10(1): 36

[11] Bardhan A, Abraham TJ, Sar TK, Rajisha R, Panda SK, Patil PK. Pharmacokinetics and residues of florfenicol in Nile tilapia (Oreochromis niloticus) postoral gavage. Environmental Toxicology and Pharmacology, 2024, 108 104471

[12] Barreto F, Ribeiro C, Hoff RB, Dalla Costa T. Determination of chloramphenicol, thiamphenicol, florfenicol and florfenicol amine in poultry, swine, bovine and fish by liquid chromatography-tandem mass spectrometry. Journal of Chromatography A, 2016, 1449: 48-53

[13] Basti D, Bouchard D, Lichtenwalner A. Safety of florfenicol in the adult lobster (Homarus americanus). Journal of Zoo and Wildlife Medicine, 2011, 42(1): 131-133

[14] Boti V, Toli V, Efthymiou C, Albanis T. Screening of commonly used antibiotics in fresh and saltwater samples impacted by aquacultures: Analytical methodology, occurrence and environmental risk assessment. Sustainability, 2023, 15 9199

[15] Bowker JD, Carty D, Bowman MP. The safety of Aquaflor (50% florfenicol) administered in feed to fingerling yellow perch. North American Journal of Aquaculture, 2013, 75(4): 517-523

[16] Bowser PR, Kosoff RE, Chen CY, Wooster GA, Getchell RG, Craig JL, Lim P, Wetzlich SE, Craigmill AL, Tell LA. Florfenicol residues in Nile tilapia after 10-d oral dosing in feed: Effect of fish size. Journal of Aquatic Animal Health, 2009, 21(1): 14-17

[17] Burridge, L. and A. Holmes. 2023. An updated review of hazards associated with the use of pesticides and drugs used in the marine environment by the finfish aquaculture industry in Canada. Fisheries and Oceans Canada, Canadian Science Advisory Secretariat Research Document 2022/067. iv + 38p Ottawa, Canada. http://www.dfo-mpo.gc.ca/csas-sccs/[e-mail].

[18] Buschmann AH, Tomova A, López A, Maldonado MA, Henríquez LA, Ivanova L, Moy F, Godfrey HP, Cabello FC. Salmon aquaculture and antimicrobial resistance in the marine environment. PLoS ONE, 2012, 7(8): e42724

[19] CA. 2024. Maximum residue limits (MRLs) and risk management in recommendations (RMRs) for residues of veterinary drugs in foods. CXM 2024. Codex Alimentarius International Food Standards. FAO and WHO. https://www.fao.org/fao-who-codexalimentarius/sh-proxy/hu/?lnk=1&url=https%253A%252F%252Fworkspace.fao.org%252Fsites%252Fcodex%252FStandards%252FCXM%2B2%252FMRL2e.pdf.

[20] CFIA. 2017. Aquaculture Therapeutant Residue Monitoring List. Canadian Food Inspection Agency. Canada. Retrieved from CFIA: http://www.inspection.gc.ca/food/fish-and-seafood/manuals/standards-and-methods/eng/1348608971859/1348609209602?chap= 7#s17c7.

[21] Chang Z, Chen Z, Gao H, Zhai Q, Li J. Pharmacokinetic profiles of florfenicol in spotted halibut, Verasper variegatus, at two water temperatures. Journal of Veterinary Pharmacology and Therapeutics, 2019, 42(1): 121-125

[22] Chen J, Sun R, Pan C, Sun Y, Mai B, Li QX. Antibiotics and food safety in aquaculture. Journal of Agricultural and Food Chemistry, 2020, 68(43): 11908-11919

[23] Choi S, Sim W, Jang D, Yoon Y, Ryu J, Oh J, Woo JS, Kim YM, Lee Y. Antibiotics in coastal aquaculture waters: Occurrence and elimination efficiency in oxidative water treatment processes. Journal of Hazardous Materials, 2020, 396 122585

[24] de Los Ríos-Escalante P, Barra V, Kretschmer C, Lozano-Muñoz I. Ecotoxicity of aquaculture chemotherapy - A case study in Chile. Sustainable Aquatic Research, 2024, 3(3): 169-174

[25] de Ocenda VR, Almeida‐Prieto S, Luzardo‐Álvarez A, Barja JL, Otero‐Espinar FJ, Blanco‐Méndez J. Pharmacokinetic model of florfenicol in turbot (Scophthalmus maximus): Establishment of optimal dosage and administration in medicated feed. Journal of Fish Diseases, 2017, 40(3): 411-424

[26] Di Salvo A, Della Rocca G, Terzetti E, Malvisi J. Florfenicol depletion in edible tissue of rainbow trout, Oncorhynchus mykiss (Walbaum), and sea bream, Sparus aurata L. Journal of Fish Diseases, 2013, 36(8): 685-693

[27] Duman M, Altun S, Cengiz M, Saticioglu IB, Buyukekiz AG, Sahinturk P. Genotyping and antimicrobial resistance genes of Yersinia ruckeri isolates from rainbow trout farms. Diseases of Aquatic Organisms, 2017, 125(1): 31-44

[28] Elgendy MY, Ali SE, Dayem AA, Khalil RH, Moustafa MM, Abdelsalam M. Alternative therapies recently applied in controlling farmed fish diseases: Mechanisms, challenges, and prospects. Aquaculture International, 2024, 32: 9017-9078

[29] EMA. 2018. Questions and Answers: Implementation of EMA guideline on environmental impact assessment for veterinary medicinal products in support of the VICH guidelines GL6 (Phase I) and GL38 (Phase II). Committee for Medicinal Products for Veterinary Use, EMEA/EMA/ERA/172074/2008-Rev.6, London, United Kingdom. https://www.ema.europa.eu/en/documents/other/questions-and-answers-implementation-cvmp-guideline-environmental-impact-assessment-veterinary-medicinal-products-support-vich-guidelines-gl6-phase-i-and-gl38-phase-ii_en.pdf.

[30] EMA. 2025. European sales and use of antimicrobials for veterinary medicine (ESUAvet). Annual surveillance report for 2023. EMA/CVMP/ESUAVET/80289/2025. https://www.ema.europa.eu/en/documents/report/european-sales-use-antimicrobials-veterinary-medicine-annual-surveillance-report-2023_en.pdf

[31] EMA/CMDv. 2023. Veterinary Medicinal Products Intended for Fish. EMA/CMDv/650880/2018. https://www.hma.eu/veterinary-medicines/cmdv/procedural-guidance/miscellaneous.html.

[32] Fang W, Li G, Zhou S, Li X, Hu L, Zhou J. Pharmacokinetics and tissue distribution of thiamphenicol and florfenicol in Pacific white shrimp Litopenaeus vannamei in freshwater following oral administration. Journal of Aquatic Animal Health, 2013, 25: 83-89

[33] FAO. 2024. The State of World Fisheries and Aquaculture 2024. Blue transformation in action. Food and Agriculture Organization, Rome. https://doi.org/10.4060/cd0683en.

[34] FDA, 2013. Environmental assessment for Aquaflor (florfenicol). Aquaflor for freshwater-reared finfish in recirculating aquaculture systems [online] EPA. Available at: https://animaldrugsatfda.fda.gov/adafda/app/search/public/document/downloadEA/113.

[35] Feng JB, Jia XP. Single dose pharmacokinetic study of flofenicol in tilapia (Oreochromis niloticus × O. aureus) held in freshwater at 22°C.. Aquaculture, 2009, 289(1-2): 129-133

[36] Feng JB, Jia XP, Li LD. Tissue distribution and elimination of florfenicol in tilapia (Oreochromis niloticus × O. aureus) after a single oral administration in freshwater and seawater at 28°C. Aquaculture, 2008, 276(1-4): 29-35

[37] Feng JB, Huang DR, Zhong M, Liu P, Dong JD. Pharmacokinetics of florfenicol and behavior of its metabolite florfenicol amine in orange‐spotted grouper (Epinephelus coioides) after oral administration. Journal of Fish Diseases, 2016, 39(7): 833-843

[38] Feng JB, Ruan HT, Chen HG, Luo JZ, Dong JD. Pharmacokinetics of florfenicol in the orange‐spotted grouper, Epinephelus coioides, following oral administration in warm seawater. Journal of the World Aquaculture Society, 2018, 49(6): 1058-1067

[39] Feng Y, Liu S, Mou C, Huang Z, Zhao Z, Zhao H, Zhou J, Li Q, Deng Y. Florfenicol-induced gut microbiome dysbiosis triggers chronic disease pathways and intestinal damage in the benthic fish (Leiocassis longirostris). Ecotoxicology and Environmental Safety, 2025, 304 119139

[40] Fernández‐Alarcón C, Miranda CD, Singer RS, López Y, Rojas R, Bello H, Domínguez M, González‐Rocha G. Detection of the floR gene in a diversity of florfenicol-resistant Gram‐negative bacilli from freshwater salmon farms in Chile. Zoonoses and Public Health, 2010, 57(3): 181-188

[41] Ferrari NA, Mainardi RM, da Silva MB, Guimarãs GD, Gaeta ML, Rocha FEP, da Silva TO, Souza AS, Baptista BC, Rocha JAK, Maturana EFL, Gonçalves DD, Barrero NML, Di Santis GW, de Pádua Pereira U. Evaluation of a florfenicol formulation for treating streptococcosis and francisellosis in Nile tilapia ( Oreochromis niloticus ): A study of safety, withdrawal period and efficacy. Microorganisms, 2025, 13 558

[42] Ferri G, Lautered C, Vergara A. Antibiotic resistance in the finfish aquaculture industry: A review. Antibiotics, 2022, 11: 1574

[43] Florêncio T, Carrasci SP, da Cruz C, da Silva AF, Marques AM, Pitelli RA. Neotropical bioindicators of ecotoxicity and environmental risk of drugs with aquaculture interest. Boletim Do Instituto De Pesca, 2014, 40(4): 569-576

[44] Fu C, Ding H, Zhang Q, Song Y, Wei Y, Wang Y, Wang B, Guo J, Qiao M. Comparative analysis of antibiotic resistance genes on a pig farm and its neighboring fish ponds in a lakeside district. Environmental Pollution, 2022, 303 119180

[45] Fukui H, Fujihara Y, Kano T. In vitro and in vivo antibacterial activities of florfenicol, a new fluorinated analog of thiamphenicol, against fish pathogens. Fish Pathology, 1987, 22(4): 201-207

[46] Gaikowski MP, Wolf JC, Endris RG, Gingerich WH. Safety of aquaflor (florfenicol, 50% type A medicated article), administered in feed to channel catfish, Ictalurus punctatus. Toxicologic Pathology, 2003, 31(6): 689-697

[47] Gaikowski MP, Mushtaq M, Cassidy P, Meinertz JR, Schleis SM, Sweeney D, Endris RG. Depletion of florfenicol amine, a marker residue of florfenicol, from the edible fillet of tilapia (Oreochromis niloticus x O. niloticus and O. niloticus x O. aureus) following florfenicol administration in feed. Aquaculture, 2010, 301(1-4): 1-6

[48] Gaikowski MP, Wolf JC, Schleis SM, Tuomari D, Endris RG. Safety of florfenicol administered in feed to tilapia (Oreochromis sp.). Toxicologic Pathology, 2013, 41(4): 639-652

[49] Gaikowski MP, Whitsel MK, Charles S, Schleis SM, Crouch LS, Endris RG. Depletion of florfenicol amine in tilapia (Oreochromis sp.) maintained in a recirculating aquaculture system following Aquaflor®‐medicated feed therapy. Aquaculture Research, 2015, 46(8): 1842-1857

[50] Gaunt P, Endris R, Khoo L, Leard AT, Jack S, Santucci T, Katz T, Radecki SV, Simmons R. Preliminary assessment of the tolerance and efficacy of florfenicol against Edwardsiella ictaluri administered in feed to channel catfish. Journal of Aquatic Animal Health, 2003, 15(3): 239-247

[51] Gaunt PS, Langston C, Wrzesinski C, Gao D, Adams P, Crouch L, Sweeney D, Endris R. Single intravenous and oral dose pharmacokinetics of florfenicol in the channel catfish (Ictalurus punctatus). Journal of Veterinary Pharmacology and Therapeutics, 2012, 35(5): 503-507

[52] Gaunt PS, Langston C, Wrzesinski C, Gao D, Adams P, Crouch L, Sweeney D, Endris R. Multidose pharmacokinetics of orally administered florfenicol in the channel catfish (Ictalurus punctatus). Journal of Veterinary Pharmacology and Therapeutics, 2013, 36(5): 502-506

[53] Guo R, Zhang Y, Zhang X, Zhang Q, Cheng R, Mostafizur RMd, Liu Y. Effects of florfenicol exposure on growth, development and antioxidant capacity of flounder Paralichthys olivaceus larvae at different developmental stages. Journal of Oceanology and Limnology, 2020, 38: 550-559

[54] Guo F, Wang Y, Peng J, Huang H, Tu X, Zhao H, Zhan N, Rao Z, Zhao G, Yang H. Occurrence, distribution, and risk assessment of antibiotics in the aquatic environment of the Karst Plateau wetland of Yangtze River basin, Southwestern China. International Journal of Environmental Research and Public Health, 2022, 19: 7211

[55] Guo X, Chen H, Tong Y, Wu X, Tang C, Qin X, Guo J, Li P, Wang Z, Liu W, Mo J. A review on the antibiotic florfenicol: Occurrence, environmental fate, effects, and health risks. Environmental Research, 2024, 244 117934

[56] Hiller CX, Hübner U, Fajnorova S, Schwartz T, Drewes JE. Antibiotic microbial resistance (AMR) removal efficiencies by conventional and advanced wastewater treatment processes: A review. Science of the Total Environment, 2019, 685 596e608

[57] Horsberg TE, Hoff KA, Nordmo R. Pharmacokinetics of florfenicol and its metabolite florfenicol amine in Atlantic salmon. Journal of Aquatic Animal Health, 1996, 8(4): 292-301

[58] Hossain A, Habibullah-Al-Mamun M, Nagano I, Masunaga S, Kitazawa D, Matsuda H. Antibiotics, antibiotic-resistant bacteria, and resistance genes in aquaculture: Risks, current concern, and future thinking. Environmental Science and Pollution Research, 2022, 29(8): 11054-11075

[59] Huang Y, Chen X, Wang H, Zhao H, Luo Y, Wu Z. Pharmacokinetics of florfenicol in blunt-snout bream (Megalobrama amblycephala) at two water temperatures with single-dose oral administration. Journal of Veterinary Pharmacology and Therapeutics, 2019, 42(5): 564-571

[60] Huynh TKD, Nguyen QT, Scippo M-L, Dang THO, Devreese M, Douny C, Croubels S, Le QV, Tran MP. Pharmacokinetics, pharmacodynamics and depletion of florfenicol applied in white leg shrimp (Litopenaeus vannamei) aquaculture and impact on shrimp hepatopancreas histology. Fishes, 2025, 10 318

[61] Islam S, Riman MM, Mannan S, Lawrence ML, Abdelhamed H. Characterization and mobilization of IncA/C plasmid-mediated antibiotic resistance in Edwardsiella ictaluri. Journal of Global Antimicrobial Resistance, 2023, 33: 177-185

[62] Jang HM, Kim YB, Choi S, Lee Y, Shin SG, Unno T, Kim YM. Prevalence of antibiotic resistance genes from effluent of coastal aquaculture, South Korea. Environmental Pollution, 2018, 233: 1049-1057

[63] Jonah L, Hamoutene D, Kingsbury M, Johnson L, Fenton AJ. A data compilation of antibiotic treatments in Canadian finfish aquaculture from 2016 to 2021, and the cumulative usage of antibiotics and antiparasitic drugs at marine sites. Environmental Reviews, 2024, 32: 334-349

[64] Kang HS, Lee SB, Shin D, Jeong J, Hong JH, Rhee GS. Occurrence of veterinary drug residues in farmed fishery products in South Korea. Food Control, 2018, 85: 57-65

[65] Kim EH, Yoshida T, Aoki T. Detection of R plasmid encoded with resistance to florfenicol in Pasteurella piscicida. Fish Pathology, 1993, 28(4): 165-170

[66] Kim MJ, Hirono I, Kurokawa K, Maki T, Hawke J, Kondo H, Santos MD, Aoki T. Complete DNA sequence and analysis of the transferable multiple-drug resistance plasmids (R plasmids) from Photobacterium damselae subsp. piscicida isolates collected in Japan and the United States. Antimicrobial Agents and Chemotherapy, 2008, 52(2): 606-611

[67] Kim Y, Jung J, Kim M, Park J, Boxall A, Choi K. Prioritizing veterinary pharmaceuticals for aquatic environment in Korea. Environmental Toxicology and Pharmacology, 2008, 26(2): 167-176

[68] Kogiannou, D., C. Nikoloudaki, P. Katharios, A. Triga, and G. Rigos. 2021. Evaluation of absorption and depletion of florfenicol in European seabass Dicentrarchus labrax. Veterinary Medicine and Science 7(3):987-997. https://doi.org/10.1002/vms3.415.

[69] Kosoff RE, Chen CY, Wooster GA, Getchell RG, Bowser PR, Clifford A, Craig JL, Lim P, Wetzlich SE, Craigmill AL, Tell LA. Florfenicol residues in three species of fish after 10‐day oral dosing in feed. Journal of Aquatic Animal Health, 2009, 21(1): 8-13

[70] Kverme KO, Haugland GT, Hannisdal R, Kallekleiv M, Colquhoun DJ, Lunestad BT, Wergeland HI, Samuelsen OB. Pharmacokinetics of florfenicol in lumpfish (Cyclopterus lumpus L.) after a single oral administration. Aquaculture, 2019, 512: 734279

[71] Lai HT, Hou JH, Su CI, Chen CL. Effects of chloramphenicol, florfenicol, and thiamphenicol on growth of algae Chlorella pyrenoidosa, Isochrysis galbana, and Tetraselmis chui. Ecotoxicology and Environmental Safety, 2009, 72(2): 329-334

[72] Lassen SB, Ahsan ME, Islam SR, Zhou XY, Razzak MA, Su JQ, Brandt KK. Prevalence of antibiotic resistance genes in Pangasianodon hypophthalmus and Oreochromis niloticus aquaculture production systems in Bangladesh. Science of the Total Environment, 2022, 813 151915

[73] Li P, Zhu T, Zhou D, Lu W, Liu H, Sun Z, Ying J, Lu J, Lin X, Li K, Ying J. Analysis of resistance to florfenicol and the related mechanism of dissemination in different animal-derived bacteria. Frontiers in Cellular and Infection Microbiology, 2020, 10 369

[74] Lim JH, Kim MS, Hwang YH, Song IB, Park BK, Yun HI. Pharmacokinetics of florfenicol following intramuscular and intravenous administration in olive flounder (Paralichthys olivaceus). Journal of Veterinary Pharmacology and Therapeutics, 2011, 34(2): 206-208

[75] Lin X, Tan A, Deng Y, Liu W, Zhao F, Huang Z. High occurrence of antibiotic resistance genes in intensive aquaculture of hybrid snakehead fish. Frontiers in Marine Science, 2023, 9 1088176

[76] Liu Y-T, Ai X-H, Yang H. Pharmacokinetics of florfenicol in channel catfish (Ictalurus punctatus) at different water temperatures. Acta Hydrobiologica Sinica, 2009, 33(1): 1-6

[77] Liu W, Ming Y, Huang Z, Li P. Impacts of florfenicol on marine diatom Skeletonema costatum through photosynthesis inhibition and oxidative damages. Plant Physiology and Biochemistry, 2012, 60: 165-170

[78] Liu X, Steele JC, Meng XZ. Usage, residue, and human health risk of antibiotics in Chinese aquaculture: A review. Environmental Pollution, 2017, 223: 161-169

[79] Ljubojević Pelić D, Radosavljević V, Pelić M, Živkov Baloš M, Puvača N, Jug-Dujaković J, Gavrilović A. Antibiotic residues in cultured fish: Implications for food safety and regulatory concerns. Fishes, 2024, 9 484

[80] Lulijwa R, Rupia EJ, Alfaro AC. Antibiotic use in aquaculture, policies and regulation, health and environmental risks: A review of the top 15 major producers. Reviews in Aquaculture, 2020, 12(2): 640-663

[81] Lynch S, Thomson P, Santibañez R, Avendaño-Herrera R. Influence of florfenicol treatments on marine-sediment microbiomes: A metagenomic study of bacterial communities in proximity to salmon aquaculture in Southern Chile. Antibiotics (Basel), 2025, 14(10): 1016

[82] Mallik SK, Shahi N, Pathak R, Kala K, Patil PK, Singh B, Ravindran R, Krishna N, Pandey PK. Pharmacokinetics and biosafety evaluation of a veterinary drug, florfenicol, in rainbow trout, Oncorhynchus mykiss (Walbaum 1792) as a model cultivable fish species in temperate water. Frontiers in Pharmacology, 2023, 14 1033170

[83] Marques TV, Paschoal JAR, Barone RSC, Cyrino JEP, Rath S. Depletion study and estimation of withdrawal periods for florfenicol and florfenicol amine in pacu (Piaractus mesopotamicus). Aquaculture Research, 2018, 49(1): 111-119

[84] Martins A, Guimarães L, Guilhermino L. Chronic toxicity of the veterinary antibiotic florfenicol to Daphnia magna assessed at two temperatures. Environmental Toxicology and Pharmacology, 2013, 36(3): 1022-1032

[85] Martinsen B, Horsberg TE, Varma KJ, Sams R. Single-dose pharmacokinetic study of florfenicol in Atlantic salmon (Salmo salar) in seawater at 11°C. Aquaculture, 1993, 112(1): 1-11

[86] Matsunaga N, Hayakawa K. Estimating the impact of antimicrobial resistance. The Lancet Global Health, 2018, 6(9): e934-e935

[87] McIntosh D, Cunningham M, Ji B, Fekete FA, Parry EM, Clark SE, Zalinger ZB, Gilg IC, Danner GR, Johnson KA, Beattie M. Transferable, multiple antibiotic and mercury resistance in Atlantic Canadian isolates of Aeromonas salmonicida subsp. salmonicida is associated with carriage of an IncA/C plasmid similar to the Salmonella enterica plasmid pSN254. Journal of Antimicrobial Chemotherapy, 2008, 61(6): 1221-1228

[88] Meinertz JR, Hess KR, Bernardy JA, Gaikowski MP, Whitsel M, Endris RG. Florfenicol residues in rainbow trout after oral dosing in recirculating and flow-through culture systems. Journal of Aquatic Animal Health, 2014, 26(4): 243-250

[89] Miranda CD, Godoy FA, Lee MR. Current status of the use of antibiotics and the antimicrobial resistance in the Chilean salmon farms. Frontiers in Microbiology, 2018, 9 1284

[90] Mitchell SM, Ullman JL, Teel AL, Watts RJ. Hydrolysis of amphenicol and macrolide antibiotics: Chloramphenicol, florfenicol, spiramycin, and tylosin. Chemosphere, 2015, 134: 504-511

[91] Nightingale, J.H. 2022. Managing the release of emerging agricultural contaminants into the environment. PhD thesis. The University of Leeds. Woodhouse, Leeds, United Kingdom. https://etheses.whiterose.ac.uk/id/eprint/31363/

[92] Nonaka L, Maruyama F, Miyamoto M, Miyakoshi M, Kurokawa K, Masuda M. Novel conjugative transferable multiple drug resistance plasmid pAQU1 from Photobacterium damselae subsp. damselae isolated from marine aquaculture environment. Microbes and Environments, 2012, 27(3): 263-272

[93] Okocha RC, Olatoye IO, Adedeji OB. Food safety impacts of antimicrobial use and their residues in aquaculture. Public Health Reviews, 2018, 39(1): 21

[94] Ortiz‑Severin J, Hodar C, Stuardo C, Aguado‑Norese C, Maza F, Gonzalez M, Cambiazo V. Impact of salmon farming in the antibiotic resistance and structure of marine bacterial communities from surface seawater of a northern Patagonian area of Chile. Biological Research, 2024, 57 84

[95] Park BK, Lim JH, Kim MS, Yun HI. Pharmacokinetics of florfenicol and its metabolite, florfenicol amine, in the Korean catfish (Silurus asotus). Journal of Veterinary Pharmacology and Therapeutics, 2006, 29(1): 37-40

[96] Patil PK, Geetha R, Ravisankar T, Avunje S, Solanki HG, Abraham TJ, Vinoth SP, Jithendran KP, Alavandi SV, Vijayan KK. Economic loss due to diseases in Indian shrimp farming with special reference to Enterocytozoon hepatopenaei (EHP) and white spot syndrome virus (WSSV). Aquaculture, 2021, 533 736231

[97] Patil PK, Mishra SS, Pradhan PK, Manna SK, Abraham TJ, Solanki HG, Shahi N, Swain P, Sahoo SN, Avunje S, Sharma KSR, Geetha R, Priyadharshini P, Nagaraju VT, Paniprasad K, Kumar A, Debnath D, Panikkar P, Raja RA, Saraswathy R, Bhuvaneswari T, Mallik SK, Sood N, Kumar CB, Sanil NK, Vinoth SP, Alavandi SV, Vijayan KK, Jithendran KP, Jena JK. Usage pattern of chemicals, biologicals and veterinary medicinal products in Indian aquaculture. Reviews in Aquaculture, 2022, 14(4): 2038-2063

[98] Patil PK, Geetha R, Mishra SS, Abraham TJ, Solanki HG, Sharma KSR, Pradhan PK, Manna SK, Avunje S, Abhinaya D, Felix KT, Vinay TN, Paniprasad K, Paria A, Raja SA, Saraswathy R, Sahoo SN, Rathod R, Rameshkumar P, Baitha R, Thomas S, Dev AK, Jayanthi M, Swain P, Sanil NK, Jena JK. Unveiling the economic burden of diseases in aquatic animal food production in India. Frontiers in Sustainable Food Systems, 2025, 9 1480094

[99] Pham QV, Nguyen QT, Devreese M, Croubels S, Dang THO, Dalsgaard A, Maita M, Tran MP. Pharmacokinetics and depletion of florfenicol in striped catfish Pangasianodon hypophthalmus after oral administration. Fisheries Science, 2023, 89: 357-365

[100] Phu TM, Phuong NT, Scippo ML, Dalsgaard A. Quality of antimicrobial products used in striped catfish (Pangasianodon hypophthalmus) aquaculture in Vietnam. PLoS ONE, 2015, 10(4): e0124267

[101] Pourmolaie B, Eshraghi HR, Haghighi M, Mortazavi SA, Rohani MS. Pharmacokinetics of florfenicol administered to rainbow trout (Oncorhynchus mykiss) by oral gavages and medicated feed routes. Bulletin of Environment, Pharmacology and Life Sciences, 2015, 4(4): 14-17

[102] Qiu M, Hu A, Yu-ming MH, Zhao Y, He Y, Xu J, Lu Z. Elucidating degradation mechanisms of florfenicol in soil by stable-isotope assisted nontarget screening. Journal of Hazardous Materials, 2021, 403 123974

[103] Quadra GR, Brovini EM, Pereira RO, Guida Y. Environmental risk assessment as a tool to identify potential hotspots of bacteria resistance worldwide. Emerging Contaminants, 2023, 9 100248

[104] Rahimi NNMN, Natrah I, Loh J-Y, Ranzil FKE, Gina M, Lim S-HE, Lai K-S, Chong C-M. Phytocompounds as an alternative antimicrobial approach in aquaculture. Antibiotics, 2022, 11: 469

[105] Rairat T, Hsieh CY, Thongpiam W, Sung CH, Chou CC. Temperature-dependent pharmacokinetics of florfenicol in Nile tilapia (Oreochromis niloticus) following single oral and intravenous administration. Aquaculture, 2019, 503: 483-488

[106] Rairat T, Kuo YS, Chang CC, Hsieh CY, Chou CC. Bath immersion pharmacokinetics of florfenicol in Nile tilapia (Oreochromis niloticus). Journal of Veterinary Pharmacology and Therapeutics, 2020, 43(6): 520-526

[107] Rairat T, Thongpiam W, Hsieh CY, Liu YK, Tunkijjanukij S, Chou CC. Salinity-dependent pharmacokinetics of florfenicol in Nile tilapia ( Oreochromis niloticus ) and its implication in optimal dosing regimen. Aquaculture, 2020, 519: 734900 10.101/j.aquaculture.2019.734900

[108] Rairat T, Chen SM, Lu YP, Hsu JCN, Liu YK, Chou CC. Determination of temperature-dependent optimal oral doses of florfenicol and corresponding withdrawal times in Nile tilapia (Oreochromis niloticus) reared at 25 and 30°C. Aquaculture, 2022, 561 738719

[109] Rairat T, Liu YK, Hsu JCN, Hsieh CY, Chuchird N, Chou CC. Combined effects of temperature and salinity on the pharmacokinetics of florfenicol in Nile tilapia (Oreochromis niloticus) reared in brackishwater. Frontiers in Veterinary Science, 2022, 9 826586

[110] Rairat T, Kumphaphat S, Chuchird N, Srisapoome P, Phansawat P, Keetanon A, Liu YK, Chou CC. Pharmacokinetics, optimal dosages and withdrawal time of florfenicol in Asian seabass (Lates calcarifer) after oral administration via medicated feed. Journal of Fish Diseases, 2023, 46(1): 75-84

[111] Reda RM, Ibrahim RE, Ahmed ENG, El-Bouhy ZM. Effect of oxytetracycline and florfenicol as growth promoters on the health status of cultured Oreochromis niloticus. Egyptian Journal of Aquatic Research, 2013, 39(4): 241-248

[112] Ren X, Pan L, Wang L. Tissue distribution, elimination of florfenicol and its effect on metabolic enzymes and related genes expression in the white shrimp Litopenaeus vannamei following oral administration. Aquaculture Research, 2016, 47: 1584-1595

[113] Ren X, Qin Y, Zhang Y, Xie J, Diao X, Altaf MM. Regional distribution differences of antibiotics in tropical marine aquaculture area: Insights into antibiotic management and risk assessment. Science of the Total Environment, 2024, 954 176391

[114] Sáenz JS, Marques TV, Barone RSC, Cyrino JEP, Kublik S, Nesme J, Schloter M, Rath S, Vestergaard G. Oral administration of antibiotics increased the potential mobility of bacterial resistance genes in the gut of the fish Piaractus mesopotamicus. Microbiome, 2019, 7(1): 1-14

[115] Salma U, Hossain A, Shafiujjaman Md, Nishimura Y, Tokumura M, Tanoue R, Kunisue T, Watanabe K, Raknuzzaman M, Noro K, Amagai T, Makino M. Occurrence, risks, and mitigation of antibiotic pollution in Bangladeshi aquaculture systems. Environmental Chemistry and Ecotoxicology, 2025, 7: 351-363

[116] Samuelsen OB, Bergh Ø, Ervik A. Pharmacokinetics of florfenicol in cod Gadus morhua and in vitro antibacterial activity against Vibrio anguillarum. Diseases of Aquatic Organisms, 2003, 56(2): 127-133

[117] Sargenti M, Bartolacci S, Luciani A, Di Biagio K, Baldini M, Galarini R, Giusepponi D, Capuccella M. Investigation of the correlation between the use of antibiotics in aquaculture systems and their detection in aquatic environments: A case study of the Nera River aquafarms in Italy. Sustainability, 2020, 12(12): 5176

[118] Schafer TW, Moss ELJrNagabhusan TL, Miller GHNelson JD, Grassi C. Novel fluorine-containing analogs of chloramphenicol and thiamphenicol: Antibacterial and biological properties. Current Chemotherapy and Infectious Disease, 1980, Washington, DC. American Society for Microbiology: 444-4461

[119] Schar D, Klein EY, Laxminarayan R, Gilbert M, Van Boeckel TP. Global trends in antimicrobial use in aquaculture. Scientific Reports, 2020, 10(1): 21878

[120] Sharma KSR, Sumithra TG, Rameshkumar P, Anikuttan K, Gop AP, Joshy A, Prasad V, Suja G, Rajisha R, Panda SK, Tamilmani G. Assessment of biosafety and fillet residues after florfenicol exposures in Trachinotus blochii to ensure safe applications in disease incidences. Turkish Journal of Fisheries and Aquatic Sciences, 2023, 23(7): TRJFAS22862

[121] Shiroma LS, Soares MP, Cardoso IL, Ishikawa MM, Jonsson CM, Queiroz SCN. Evaluation of health and environmental risks for juvenile tilapia (Oreochromis niloticus) exposed to florfenicol. Heliyon, 2020, 6(12): e05716

[122] Shiry N, Derakhshesh N, Rahbar A. Determination of florfenicol residues in the edible tissue of shrimp reared in Bushehr province’s farms (Iran). Journal of Marine Medicine, 2021, 3(2): 91-96

[123] Singh A, Pratap SG, Raj A. Occurrence and dissemination of antibiotics and antibiotic resistance in aquatic environment and its ecological implications: A review. Environmental Science and Pollution Research, 2024, 31: 47505-47529

[124] Soltan M, Agouz H, Mohamed M. Effect of oxytetracycline and florfenicol drugs on the physiological activities and its residues of Oreochromis niloticus. Egyptian Journal of Aquatic Biology and Fisheries, 2013, 17(4): 25-36

[125] Song C, Zhang C, Fan L, Qiu L, Wu W, Meng S, Hu G, Kamira B, Chen J. Occurrence of antibiotics and their impacts to primary productivity in fishponds around Tai Lake, China. Chemosphere, 2016, 161: 127-135

[126] Straus DL, Bowker JD, Bowman MP, Carty D, Mitchell AJ, Farmer BD. Safety of Aquaflor-medicated feed to sunshine bass. North American Journal of Aquaculture, 2012, 74(1): 1-7

[127] Sun Z, Zhang L, Dong D, Guo Z. Optimizing the multimedia fate model for characterizing environmental risks of florfenicol in seasonally ice-covered reservoirs. Environmental Pollution, 2023, 323 121299

[128] Suzuki Y, Okamoto S. The enzymatic acetylation of chloramphenicol by the multiple drug-resistant Escherichia coli carrying R factor. Journal of Biological Chemistry, 1967, 242(20): 4722-4730

[129] Syriopoulou VP, Harding AL, Goldmann DA, Smith AL. In vitro antibacterial activity of fluorinated analogs of chloramphenicol and thiamphenicol. Antimicrobial Agents and Chemotherapy, 1981, 19(2): 294-297

[130] Tan BSY, Mohan L, Watthanaworawit W, Ngamprasertchai T, Nosten FH, Ling C, Bifani P. Detection of florfenicol resistance in opportunistic Acinetobacter spp. infections in rural Thailand. Frontiers in Microbiology, 2024, 15: 1368813

[131] Tipmongkolsilp N, Limpanon Y, Patamalai B, Lusanandana P, Wongtavatchai J. Oral medication with florfenicol for black tiger shrimps Penaeus monodon. Thai Journal of Veterinary Medicine, 2006, 36: 39-47

[132] Tomova A, Ivanova L, Buschmann AH, Rioseco ML, Kalsi RK, Godfrey HP, Cabello FC. Antimicrobial resistance genes in marine bacteria and human uropathogenic Escherichia coli from a region of intensive aquaculture. Environmental Microbiology Reports, 2015, 7(5): 803-809

[133] Torres-Corral Y, Santos Y. Predicting antimicrobial resistance of Lactococcus garvieae: PCR detection of resistance genes versus MALDI-TOF protein profiling. Aquaculture, 2022, 553 738098

[134] Trif E, Cerbu C, Olah D, Zăblău SD, Spînu M, Potârniche AV, Pall E, Brudașcă F. Old antibiotics can learn new ways: A systematic review of florfenicol use in veterinary medicine and future perspectives using nanotechnology. Animals, 2023, 13 1695

[135] Türe M, Taçbaş E, Baydan E, Kutlu İ, Altuntaş C, Aydın FG, Arslanbaş E, Yücel Tenekeci G. Determination of the muscle residue levels and withdrawal time of florfenicol in healthy and experimentally Lactococcus garvieae infected rainbow trout (Oncorhynchus mykiss, Walbaum 1792) grown in the Black Sea water. Aquaculture Research, 2019, 50(7): 1964-1972

[136] USFDA. 2025. Approved Aquaculture Drugs. United States Food and Drug Administration. https://www.fda.gov/animal-veterinary/aquaculture/approved-aquaculture-drugs Accessed 22 September 2025

[137] USFWS. 2020. Approved Drugs for Use in Aquaculture, Third ed. U.S. Fish and Wildlife Service’s (USFWS) Aquatic Animal Drug Approval Partnership Program, American Fisheries Society’s Fish Culture and Fish Health Sections. Association of Fish and Wildlife Agencies and Fisheries and Water Resources Policy Committee’s Drug Approval Working Group. https://www.fws.gov/sites/default/files/documents/3rd-Edition-Quick-Reference-Guide-to-Approved-for-Use-in-Aquaculture-Drugs.pdf

[138] VICH. 2003. Environmental Impact Assessment (EIAs) for Veterinary Medicinal Products (VMPs) - Phase II Draft Guidance. London: CVMP/VICH GL 38. CVMP/VICH/790/03-Consultation. https://www.ema.europa.eu/en/documents/scientific-guideline/vich-gl38-environmental-impact-assessments-veterinary-medicinal-products-vmps-phase-ii_en.

[139] Vincent AT, Trudel MV, Paquet VE, Boyle B, Tanaka KH, Dallaire-Dufresne S, Daher RK, Frenette M, Derome N, Charette SJ. Detection of variants of the pRAS3, pAB5S9, and pSN254 plasmids in Aeromonas salmonicida subsp. salmonicida: Multidrug resistance, interspecies exchanges, and plasmid reshaping.. Antimicrobial Agents and Chemotherapy, 2014, 58(12): 7367-7374

[140] Wang W, Dai X, Li Z, Meng Q. Tissue distribution and elimination of florfenicol in topmouth culter (Culter alburnus) after oral administration. Czech Journal of Food Sciences, 2009, 27(3): 214-221

[141] Wang W, Zhou L, Gu X, Chen H, Zeng Q, Mao Z. Occurrence and distribution of antibiotics in surface water impacted by crab culturing: A case study of Lake Guchenghu, China. Environmental Science and Pollution Research, 2018, 25(23): 22619-22628

[142] Wang N, Shen W, Zhang S, Cheng J, Qi D, Hua J, Kang G, Qiu H. Occurrence and distribution of antibiotics in coastal water of the Taizhou Bay, China: Impacts of industrial activities and marine aquaculture. Environmental Science and Pollution Research, 2022, 29(54): 81670-81684

[143] Wang Q, Zhou X, Liu Y, Ding Q, Wu Z, Deng J, Zuo J, Yuan L, Shao P, Cheng B, Gao L. Bacterial community and antibiotic resistance gene profiles of fish gut contents and their aquaculture environment in Tianjin, China. Aquaculture Journal, 2022, 2: 269-284

[144] Wang J, Wang X, Zheng X, Yang Y, He Z, Zhang L, Liao Q. Effects of florfenicol on methane accumulation and changes in the structure of the prokaryotic community in a water–sediment system. Science of the Total Environment, 2022, 847 157444

[145] Wang W, Li J, Fang M, Chang Y, Wang T, Wang X, Liu H, Zou W, Cao Z. Environmental risk control of florfenicol in water: From technology selection to mechanism discussion. Journal of Environmental Chemical Engineering, 2024, 12(6): 114852

[146] Watts JEM, Schreier HJ, Lanska L, Hale MS. The rising tide of antimicrobial resistance in aquaculture: Sources, sinks and solutions. Marine Drugs, 2017, 15(6): 158

[147] Wei CF, Chang SK, Shien JH, Kuo HC, Chen WY, Chou CC. Synergism between two amphenicols of antibiotics, florfenicol and thiamphenicol, against Staphylococcus aureus. Veterinary Record, 2016, 178(13): 319-319

[148] Welch TJ, Evenhuis J, White DG, McDermott PF, Harbottle H, Miller RA, Griffin M, Wise D. IncA/C plasmid-mediated florfenicol resistance in the catfish pathogen Edwardsiella ictaluri. Antimicrobial Agents and Chemotherapy, 2009, 53(2): 845-846

[149] WOAH 2021. OIE List of Antimicrobial Agents of Veterinary Importance. World Organization for Animal Health, Paris, France. https://www.woah.org/app/uploads/2021/06/a-oie-list-antimicrobials-june2021.pdf

[150] WOAH, 2024. Annual Report on Antimicrobial Agents Intended for Use in Animals. 8th Report. World Organization for Animal Health. Paris, France. p33. https://www.woah.org/app/uploads/2024/05/woah-amu-report-2024-final.pdf.

[151] Wrzesinski C, Crouch L, Gaunt P, Holifield D, Bertrand N, Endris R. Florfenicol residue depletion in channel catfish, Ictalurus punctatus (Rafinesque). Aquaculture, 2006, 253(1–4): 309-316

[152] Wu C, Zhang X, Liang J, Li Q, Lin H, Lin C, Liu H, Zhou D, Lu W, Sun Z, Lin X. Characterization of florfenicol resistance genes in the coagulase-negative Staphylococcus (CoNS) isolates and genomic features of a multidrug-resistant Staphylococcus lentus strain H29. Antimicrobial Resistance and Infection Control, 2021, 10(1): 9

[153] Yang F, Yang F, Kong T, Wang G, Bai D, Liu B. Pharmacokinetics of florfenicol and its metabolite florfenicol amine in crucian carp (Carassius auratus) at three temperatures after one single intramuscular injection. Journal of Veterinary Pharmacology and Therapeutics, 2018, 41(5): 739-745

[154] Yang F, Yang F, Wang G, Kong T, Liu B. Pharmacokinetics of florfenicol and its metabolite florfenicol amine in crucian carp (Carassius auratus) at three temperatures after single oral administration. Aquaculture, 2019, 503: 446-451

[155] Yang F, Yang F, Wang G, Kong T, Wang H, Zhang C. Effects of water temperature on tissue depletion of florfenicol and its metabolite florfenicol amine in crucian carp (Carassius auratus gibelio) following multiple oral doses. Aquaculture, 2020, 515 734542

[156] Yasunaga N, Yasumoto S. Therapeutic effect of florfenicol on experimentally induced pseudotuberculosis in yellowtail. Fish Pathology, 1988, 23(1): 1-5

[157] Yikilmaz Y, Filazi A. Detection of florfenicol residues in salmon trout via GC–MS. Food Analytical Methods, 2015, 8(4): 1027-1033

[158] Yue G, Guo C. Strategies for managing major diseases in Asian seabass aquaculture. Animal Diseases, 2025, 5(1): 6

[159] Zeng Q, Liao C, Terhune J, Wang L. Impacts of florfenicol on the microbiota landscape and resistome as revealed by metagenomic analysis. Microbiome, 2019, 7(1): 155

[160] Zhang Z, Li Y, Hu M, Yu A. Comparative transcriptome profiling reveals a mechanism of Streptococcus agalactiae resistance to florfenicol. Microbial Pathogenesis, 2020, 142 104098

[161] Zhang L, Du S, Zhang X, Lyu G, Dong D, Hua X, Zhang W, Guo Z. Occurrence, distribution, and ecological risk of pharmaceuticals in a seasonally ice-sealed river: From ice formation to melting. Journal of Hazardous Materials, 2020, 389 122083

[162] Zhang Y, Zhang X, Guo R, Zhang Q, Cao X, Suranjana M, Liu Y. Effects of florfenicol on growth, photosynthesis and antioxidant system of the nontarget organism Isochrysis galbana. Comparative Biochemistry and Physiology Part c: Toxicology and Pharmacology, 2020, 233 108764

[163] Zhang MQ, Yang JL, Lai XX, Li W, Zhan MJ, Zhang CP, Jiang JZ, Shu H. Effects of integrated multitrophic aquaculture on microbial communities, antibiotic resistance genes, and cultured species: A case study of four mariculture systems. Aquaculture, 2022, 557 738322

[164] Zhang T, Ding Y, Peng J, Dai Y, Luo S, Liu W, Ma Y. Effects of broad-spectrum antibiotic (florfenicol) on resistance genes and bacterial community structure of water and sediments in an aquatic microcosm model. Antibiotics, 2022, 11: 1299

[165] Zhang T, Peng J, Dai Y, Xie X, Luo S, Ding Y, Ma Y. Effect of florfenicol on nirS-type denitrifying communities structure of water in an aquatic microcosm model. Frontiers in Veterinary Science, 2023, 10 1205394

[166] Zong HM, Ma DY, Wang JY, Hu JT. Research on florfenicol residue in coastal area of Dalian (Northern China) and analysis of functional diversity of the microbial community in marine sediment. Bulletin of Environmental Contamination and Toxicology, 2010, 84: 245-249

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