Antimicrobials in aquaculture
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Antimicrobials destroy
bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
,
viruses A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's 1 ...
,
fungi A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...
,
algae Algae (; singular alga ) is an informal term for a large and diverse group of photosynthetic eukaryotic organisms. It is a polyphyletic grouping that includes species from multiple distinct clades. Included organisms range from unicellular mic ...
, and other microbes. The cells of bacteria (
prokaryote A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Connec ...
s), such as
salmonella ''Salmonella'' is a genus of rod-shaped (bacillus) Gram-negative bacteria of the family Enterobacteriaceae. The two species of ''Salmonella'' are ''Salmonella enterica'' and ''Salmonella bongori''. ''S. enterica'' is the type species and is fur ...
, differ from those of higher-level organisms (
eukaryote Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
s), such as fish.
Antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...
s are chemicals designed to either kill or inhibit the growth of pathogenic bacteria while exploiting the differences between prokaryotes and eukaryotes in order to make them relatively harmless in higher-level organisms. Antibiotics are constructed to act in one of three ways: by disrupting cell membranes of bacteria (rendering them unable to regulate themselves), by impeding DNA or protein synthesis, or by hampering the activity of certain enzymes unique to bacteria. Antibiotics are used in
aquaculture Aquaculture (less commonly spelled aquiculture), also known as aquafarming, is the controlled cultivation ("farming") of aquatic organisms such as fish, crustaceans, mollusks, algae and other organisms of value such as aquatic plants (e.g. lot ...
to treat diseases caused by bacteria. Sometimes the antibiotics are used to treat diseases, but more commonly antibiotics are used to prevent diseases by treating the water or fish before disease occurs. While this prophylactic method of preventing disease is profitable because it prevents loss and allows fish to grow more quickly, there are several downsides. The overuse of antibiotics can create
antibiotic-resistant Antimicrobial resistance (AMR) occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials. All classes of microbes can evolve resistance. Fungi evolve antifungal resistance. Viruses evolve antiviral resistance. ...
bacteria. Antibiotic-resistant bacteria can spontaneously arise when selective pressure to survive results in changes to the DNA sequence of a bacterium allowing that bacterium to survive antibiotic treatments. Because some of the same antibiotics are used to treat fish that are used to treat human disease, pathogenic bacteria causing human disease can also become resistant to antibiotics as a result of treatment of fish with antibiotics. For this reason, the overuse of antibiotics in treatment of fish aquaculture (among other agricultural uses) could create public health issues.


Overview

The issue has two sides. In some foreign countries, clean water supplies for aquaculture are extremely limited.Tainted Seafood Reaching U.S., Food Safety Experts Say
Nicole Gilbert, News21, 2011 (last visited Oct. 2011).
Untreated animal manure and human waste are used as feed in shrimp farms and tilapia farms in China and Thailand, in addition to the collection of waste products accumulating from inadequate sewage treatment. In order to prevent the spread of bacteria and disease in contaminated water, some foreign fish farms put U.S.-banned antibiotics into their fishmeal. However, because the more stringent growing regulations in the US increase the price of food, imports from nations without these regulations are increasing based on price and profit.SEAFOOD SAFETY, FDA Needs to Improve Oversight of Imported Seafood and Better Leverage Limited Resources
United States Government Accountability Office, April 14, 2011
Between 1995 and 2005, the first ten years of the
NAFTA The North American Free Trade Agreement (NAFTA ; es, Tratado de Libre Comercio de América del Norte, TLCAN; french: Accord de libre-échange nord-américain, ALÉNA) was an agreement signed by Canada, Mexico, and the United States that crea ...
-
WTO The World Trade Organization (WTO) is an intergovernmental organization that regulates and facilitates international trade. With effective cooperation in the United Nations System, governments use the organization to establish, revise, and e ...
era in the US, seafood imports increased 65 percent and shrimp imports increased 95 percent. Today, 80 percent of American seafood is imported, about half coming from aquaculture. China, Thailand and Vietnam together account for 44 percent of seafood imports into the United States. The FDA has been testing for chemicals in aquaculture products for over two decades. In November 2005, the testing program for aquaculture drugs was revised to include antibiotics such as
chloramphenicol Chloramphenicol is an antibiotic useful for the treatment of a number of bacterial infections. This includes use as an eye ointment to treat conjunctivitis. By mouth or by injection into a vein, it is used to treat meningitis, plague, cholera, a ...
,
fluoroquinolones A quinolone antibiotic is a member of a large group of broad-spectrum antibiotic, broad-spectrum bacteriocidals that share a bicyclic molecule, bicyclic core structure related to the substance 4-Quinolone, 4-quinolone. They are used in human and ...
, nitrofurans, and
quinolones Quinolone may refer to: * 2-Quinolone * 4-Quinolone * Quinolone antibiotic A quinolone antibiotic is a member of a large group of broad-spectrum bacteriocidals that share a bicyclic core structure related to the substance 4-quinolone. They ar ...
, as well as antimicrobial compounds like malachite green that are not approved for use in aquaculture fish. From October 1, 2006, through May 31, 2007, FDA tested samples of catfish, basa,
shrimp Shrimp are crustaceans (a form of shellfish) with elongated bodies and a primarily swimming mode of locomotion – most commonly Caridea and Dendrobranchiata of the decapod order, although some crustaceans outside of this order are refer ...
, dace, and eel from China, finding twenty-five percent of the samples to contain drug residues.Hearing on "Safety of Chinese Imports"
statement of Murray M. Lumpkin, M.D., Deputy Commissioner for International and Special Program before the Senate Committee on Commerce, Science & Transportation, July 18, 2007
FDA has approved five different drugs for use in aquaculture as long as the seafood contains less than a mandated maximum residue limit: florfenicol, sulfamerazine, chorionic gonadotropin, oxytetracycline dihydrate, oxytetracycline hydrochloride, as well as a drug combination of sulfadimethoxine and ormetoprim. FDA has approved two drugs—formalin and hydrogen peroxide—for which it has not set a tolerance. The FDA now enforces regulations in the US requiring testing of certain imported products for antimicrobial agents under Import Alert 16-131.FDA Import Alert 16-131, http://www.accessdata.fda.gov/cms_ia/importalert_33.html The Import Alert provides that the use of antimicrobials during the various stages of aquaculture, including malachite green, nitrofurans, fluoroquinolones, and gentian violet, may contribute to an increase of antimicrobial resistance in human pathogens and that prolonged exposure to nitrofurans, malachite green, and gentian violet has been shown to have a carcinogenic affect. In a consumer brochure, the FDA describes the reasoning for enforcement under the import alert:
After FDA repeatedly found that farm-raised seafood from China was contaminated, the agency announced on June 28, 2007, a broader import control of all farm-raised catfish, basa, shrimp, dace(related to carp), and eel from China. During targeted sampling, from October 2006 through May 2007, FDA repeatedly found that farm-raised seafood from China was contaminated with antimicrobial agents that are not approved for use in the United States. More specifically, the antimicrobials nitrofuran, malachite green, gentian violet, and fluoroquinolones, were detected.
Due to limitations on funding and resources, U.S.
Government Accountability Office The U.S. Government Accountability Office (GAO) is a legislative branch government agency that provides auditing, evaluative, and investigative services for the United States Congress. It is the supreme audit institution of the federal govern ...
states that only 1% of seafood, compared with 2% of all imports, is inspected and only 0.1% of all seafood is tested for antibiotic residue.


Example antimicrobials


Copper alloys

Recently,
copper alloys Copper alloys are metal alloys that have copper as their principal component. They have high resistance against corrosion. The best known traditional types are bronze, where tin is a significant addition, and brass, using zinc instead. Both of th ...
have become important netting materials in
aquaculture Aquaculture (less commonly spelled aquiculture), also known as aquafarming, is the controlled cultivation ("farming") of aquatic organisms such as fish, crustaceans, mollusks, algae and other organisms of value such as aquatic plants (e.g. lot ...
(the farming of aquatic organisms including
fish farming upright=1.3, Salmon farming in the sea (mariculture) at Loch Ainort, Isle of Skye">mariculture.html" ;"title="Salmon farming in the sea (mariculture">Salmon farming in the sea (mariculture) at Loch Ainort, Isle of Skye, Scotland Fish farming or ...
). Various other materials including
nylon Nylon is a generic designation for a family of synthetic polymers composed of polyamides ( repeating units linked by amide links).The polyamides may be aliphatic or semi-aromatic. Nylon is a silk-like thermoplastic, generally made from petro ...
,
polyester Polyester is a category of polymers that contain the ester functional group in every repeat unit of their main chain. As a specific material, it most commonly refers to a type called polyethylene terephthalate (PET). Polyesters include natural ...
,
polypropylene Polypropylene (PP), also known as polypropene, is a thermoplastic polymer used in a wide variety of applications. It is produced via chain-growth polymerization from the monomer propylene. Polypropylene belongs to the group of polyolefins and ...
,
polyethylene Polyethylene or polythene (abbreviated PE; IUPAC name polyethene or poly(methylene)) is the most commonly produced plastic. It is a polymer, primarily used for packaging ( plastic bags, plastic films, geomembranes and containers including bo ...
, plastic-coated welded
wire Overhead power cabling. The conductor consists of seven strands of steel (centre, high tensile strength), surrounded by four outer layers of aluminium (high conductivity). Sample diameter 40 mm A wire is a flexible strand of metal. Wire is c ...
,
rubber Rubber, also called India rubber, latex, Amazonian rubber, ''caucho'', or ''caoutchouc'', as initially produced, consists of polymers of the organic compound isoprene, with minor impurities of other organic compounds. Thailand, Malaysia, and ...
, patented twine products (Spectra, Dyneema), and
galvanized steel Galvanization or galvanizing ( also spelled galvanisation or galvanising) is the process of applying a protective zinc coating to steel or iron, to prevent rusting. The most common method is hot-dip galvanizing, in which the parts are submerged ...
are also used for netting in
aquaculture Aquaculture (less commonly spelled aquiculture), also known as aquafarming, is the controlled cultivation ("farming") of aquatic organisms such as fish, crustaceans, mollusks, algae and other organisms of value such as aquatic plants (e.g. lot ...
fish enclosures around the world. All of these materials are selected for a variety of reasons, including design feasibility,
material strength The field of strength of materials, also called mechanics of materials, typically refers to various methods of calculating the stresses and strains in structural members, such as beams, columns, and shafts. The methods employed to predict the re ...
, cost, and
corrosion resistance Corrosion is a natural process that converts a refined metal into a more chemically stable oxide. It is the gradual deterioration of materials (usually a metal) by chemical or electrochemical reaction with their environment. Corrosion engine ...
. What sets copper alloys apart from the other materials used in fish farming is that copper alloys are antimicrobial (For information about the antimicrobial properties of copper and its alloys, see
Antimicrobial properties of copper Copper and its alloys (brasses, bronzes, cupronickel, copper-nickel-zinc, and others) are natural antimicrobial materials. Ancient civilizations exploited the antimicrobial properties of copper long before the concept of microbes became understood ...
and
Antimicrobial copper alloy touch surfaces Antimicrobial copper-alloy touch surfaces can prevent frequently touched surfaces from serving as reservoirs for the spread of pathogenic microbes. This is especially true in healthcare facilities, where harmful viruses, bacteria, and fungi coloni ...
). In the
marine environment Marine habitats are habitats that support marine life. Marine life depends in some way on the saltwater that is in the sea (the term ''marine'' comes from the Latin ''mare'', meaning sea or ocean). A habitat is an ecological or environmental ...
, the antimicrobial/algaecidal properties of copper alloys prevent
biofouling Biofouling or biological fouling is the accumulation of microorganisms, plants, algae, or small animals where it is not wanted on surfaces such as ship and submarine hulls, devices such as water inlets, pipework, grates, ponds, and rivers that ...
, which can briefly be described as the undesirable accumulation, adhesion, and growth of
microorganisms A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in olde ...
, plants,
algae Algae (; singular alga ) is an informal term for a large and diverse group of photosynthetic eukaryotic organisms. It is a polyphyletic grouping that includes species from multiple distinct clades. Included organisms range from unicellular mic ...
,
tube worms A tubeworm is any worm-like sessility (zoology), sessile invertebrate that anchors its tail to an underwater surface and secretes around its body a mineral tube, into which it can withdraw its entire body. Tubeworms are found among the following t ...
,
barnacles A barnacle is a type of arthropod constituting the subclass Cirripedia in the subphylum Crustacea, and is hence related to crabs and lobsters. Barnacles are exclusively marine, and tend to live in shallow and tidal waters, typically in erosive ...
,
mollusks Mollusca is the second-largest phylum of invertebrate animals after the Arthropoda, the members of which are known as molluscs or mollusks (). Around 85,000  extant species of molluscs are recognized. The number of fossil species is esti ...
, and other organisms on man-made marine structures. By inhibiting microbial growth, copper alloy aquaculture pens avoid the need for costly net changes that are necessary with other materials. The resistance of organism growth on copper alloy nets also provides a cleaner and healthier environment for farmed fish to grow and thrive. In addition to their antifouling benefits, copper alloys have strong structural and corrosion-resistant properties in marine environments. Brass alloy netting cages are also currently being deployed in commercial-scale aquaculture operations in Asia, South America, and the USA. See antimicrobial properties of brass


Methylene blue

Methylene blue Methylthioninium chloride, commonly called methylene blue, is a salt used as a dye and as a medication. Methylene blue is a thiazine dye. As a medication, it is mainly used to treat methemoglobinemia by converting the ferric iron in hemoglobin ...
is used in aquaculture and by tropical fish hobbyists as a treatment for fungal infections. It can also be effective in treating fish infected with ''ich'', the parasitic
protozoa Protozoa (singular: protozoan or protozoon; alternative plural: protozoans) are a group of single-celled eukaryotes, either free-living or parasitic, that feed on organic matter such as other microorganisms or organic tissues and debris. Histo ...
'' Ichthyophthirius multifiliis''. It is usually used to protect newly laid fish eggs from being infected by fungus or bacteria. This is useful when the hobbyist wants to artificially hatch the fish eggs. Methylene Blue is also very effective when used as part of a "medicated fish bath" for treatment of ammonia, nitrite, and cyanide poisoning as well as for topical and internal treatment of injured or sick fish as a "first response".


Ozone

Ozone Ozone (), or trioxygen, is an inorganic molecule with the chemical formula . It is a pale blue gas with a distinctively pungent smell. It is an allotrope of oxygen that is much less stable than the diatomic allotrope , breaking down in the lo ...
is added to seawater and used for the surface disinfection of
haddock The haddock (''Melanogrammus aeglefinus'') is a saltwater ray-finned fish from the family Gadidae, the true cods. It is the only species in the monotypic genus ''Melanogrammus''. It is found in the North Atlantic Ocean and associated seas where ...
and
Atlantic halibut The Atlantic halibut (''Hippoglossus hippoglossus'') is a flatfish of the family Pleuronectidae. They are demersal fish living on or near sand, gravel or clay bottoms at depths of between . The halibut is among the largest Teleostei, teleost (bon ...
eggs against nodavirus. Nodavirus is a lethal and vertically transmitted virus which causes severe mortality in fish. Haddock eggs should not be treated with high ozone level as eggs so treated did not hatch and died after 3–4 days.


Some problematic antimicrobials


Malachite green

In 1983, the FDA banned the use of malachite green in aquaculture. Toxicity studies have shown that this chemical can have serious toxic side effects. Malachite green is not actually an antibiotic, but has antibiotic properties. Malachite green is somewhat stable within the environment and, therefore, is detectable in fish that were treated with the chemical at some point even after treatment has discontinued. After more stringent testing and inspection by the governments of Western Countries, the use of malachite green began to wane and other drugs began to become more prevalent.


Chloramphenicol

While the U.S. has tested farm-raised shrimp for
chloramphenicol Chloramphenicol is an antibiotic useful for the treatment of a number of bacterial infections. This includes use as an eye ointment to treat conjunctivitis. By mouth or by injection into a vein, it is used to treat meningitis, plague, cholera, a ...
since 1994, over the last decade the FDA developed a more sensitive testing methodology and changed the levels of detection for chloramphenicol in response to increasing discovery of traces of chloramphenicol in imports. In response to the US discovery of chloramphenicol in imported shrimp and subsequent increased testing sensitivity, the use of this compound in aquaculture began to decrease.


Gentian violet

Gentian violet, also known as crystal violet has antibacterial, antifungal, and antiparasitic properties. This compound was used during the World War I era as a topical antiseptic, but has been replaced in modern times with more modern treatments. The FDA prohibits the use of gentian violet in aquaculture because of numerous studies showing increased risk of certain cancers related to the compound and a showing that the chemical is bioavailable in fish when used in aquaculture.


Nitrofurans

Nitrofurans are broad spectrum antibiotics, being effective against Gram-positive and Gram-negative bacteria. In 1991, the FDA withdrew several approved food animal nitrofuran products as a result of research showing nitrofurazone, one of the nitrofurans, can produce mammary tumors in rats and ovarian tumors in mice. The FDA also concluded that some people may be hypersensitive to this product."Detention Without Physical Examination of Seafood Products Due to Nitrofurans"
''Import Alert'' #16-129, published 06/29/2011 (last visited Oct. 2011).
The FDA states, "Absolutely, no extra-label use of the nitrofurans is permitted in any food animals, including seafood." The FDA currently detains certain seafood imports without physical examination due to nitrofuran use by the producer.


Floroquinolones

Fluoroquinolones have been prohibited from extra-label use in the U.S. and many other parts of the world in aquaculture because of public health concern about the development of such antimicrobial resistance. Chinese authorities have acknowledged permitting the use of fluoroquinolones in aquaculture, even though the use of fluoroquinolones in food animals may increase antibiotic resistance in human pathogens compromising the effectiveness of the use of this critically important class of antibiotics in human medicine. The Chinese government has established a higher maximum residue limit than the US and research in China has shown that the Chinese are effectively meeting the Chinese limits.He, X, et al., "Residues of fluoroquinolones in marine aquaculture environment of the Pearl River Delta, South China", ''Environ Geochem Health''. 2011 Sep 1 Because of concerns about the presence of fluoroquinolones in the food supply, not only in aquaculture, but also in foods like honey, the U.S. is continuing to develop methods and strategies to detect illegal residues and prevent their introduction into the U.S. food supply.


References

{{fishing industry topics, expanded=aquaculture Aquaculture Food politics Antimicrobials