Antibiotics, antibiotic resistant bacteria, and resistance genes in aquaculture: risks, current concern, and future thinking

Aquaculture is remarkably one of the most promising industries among the food-producing industries in the world. Antibiotics are usually present at sub therapeutic levels in the aquaculture environment, which increases the selective pressure on the resistant bacteria and stimulates resistant gene transfer in the aquatic environment. This review suggests an initiative to make a uniform antibiotic registration process, to establish the maximum residue levels (MRLs) for fish/shrimp and to ensure the use of only aquaculture antibiotics in fish and shellfish farming globally.

Aquaculture is one of the fastest growing sectors among the animal production sectors in the world and contributes nearly 80 million tons of fishes to the global production (FAO, 2018). Currently, 152 million tons of food fishes is being used for human consumption where more than 50% is coming from aquaculture.

“Globally, the fish consumption per capita rapidly increased from 9.9 to 20.3 kg between 1960 and 2016 (FAO, 2018).”

However, the sustainable development of this rapidly growing sector is one of the major concerns, particularly in terms of supply of safe and edible fishes. Aquaculture farming practices are changing worldwide from traditional to intensive farming systems, leading to stock a greater number of fish/shellfishes in lesser spaces of water, notably increasing the risk of transmissible and infectious diseases (Santos and Ramos, 2018).

In addition, aquaculture farming mainly depends on artificial feeds and sometimes overuse, misuse, or overfeeding of feeds are common scenarios due to lack of farmer’s proper knowledge and institutional education specifically in developing countries. Subsequently, the culture environment changed from its natural to obnoxious condition which enhances the chances of disease burden, particularly infectious diseases.

For the reduction of disease burden, the applications of antibiotics in prophylactic and therapeutic purposes are very common practices to prevent bacterial infections in aquaculture (Cabello et al., 2013). Prophylactic or therapeutic applications of antibiotics in aquaculture may exert the selection pressure to the natural bacterial population and enhance the ability to produce antibiotic-resistant bacteria or resistance genes to the aquaculture environment.

Data related to antibiotic usage in aquaculture is very scarce and differs significantly from country to country. Therefore, this review includes the current antibiotic uses patterns in aquaculture, the ecological, bacterial resistance, and human health risks of antibiotics, and the current regulatory framework and future concern of antibiotic use in aquaculture worldwide.

Application of antibiotics in aquaculture

Positive effects of antibiotics

The aquaculture farmers are regularly using antibiotics as prophylactic or therapeutic purposes to minimize the occurrence and spread of bacterial infections, particularly in the countries where no alternative preventive methods being implemented.

“Antibiotics are commonly used in aquaculture to prevent and/or cure infectious diseases in Asia, Canada, Europe, the USA, and many other countries worldwide.”

Usually, antibiotics are routinely applied in

(i) prophylactic use by bath treatments or mixed with feed and

(ii) therapeutic use for the treatment of bacterial infections (Ali et al., 2016).

In addition, antibiotics particularly oxytetracycline and florfenicol are also used as growth promoter of the aquaculture species (Reda et al., 2013).

Side effects of antibiotics

In aquaculture, antibiotics are generally administered to the entire population including sick, healthy, and carrier individuals. As a result, antibiotics are mostly overused and misused in aquaculture of many countries (Santos and Ramos, 2018).

Moreover, antibiotic doses in aquaculture can be consistently higher than that of terrestrial animals farming, although the specific contamination levels are difficult to determine (Romero et al., 2012).

Due to the lack of institutional knowledge, the farmers usually overuse or misuse the antibiotics in the Asian aquaculture. Consequently, aquaculture products from different countries (Bangladesh, China, India, Malaysia, and Vietnam) have been rejected by the EU and the USA for the presence of banned antibiotics.

The use of antibiotics in aquaculture may contaminate the culture environments as well as farmed organisms through different ways where feed is one of the most important sources (Li et al., 2021). A schematic diagram of antibiotic contamination from various probable sources in aquaculture is shown in Figure 1.

Country specific use of antibiotics in aquaculture

Though antibiotics are widely used in aquaculture, the data are still very limited. The information related to antibiotic usages and residues in aquaculture products mostly reported from developed countries; however, the majority of fish and shellfishes are being produced in developing and/ or least developed Asian countries where the regulatory strategies or guideline in aquaculture are limited or almost absent (Howgate, 1998; Chuah et al., 2016; Santos and Ramos, 2018).

Moreover, the application of antibiotics in aquaculture often lack institutional training and knowledge concerning the safe and responsible use of antibiotics (Gräslund et al., 2003; Pham et al., 2015), causing an unnecessary usage that consistently goes unstated.

The numbers of antibiotics used in different countries are shown in Figure 2.

Antibiotic resistant bacteria and resistance genes in aquaculture

Aquaculture has been considered as a “genetic hotspot” for resistance gene transfer. Multiple antibiotic-resistant strains are now being frequently detected in fish/shellfish and aquaculture environment, which greatly threat the medical treatment options as well as increase the unwanted deaths (Watts et al., 2017).

“Reverter et al. (2020) reported that aquaculture of low- and middle-income countries contributed the higher levels of antibiotic-resistant bacteria.”

Antibiotic-resistant bacteria and resistance gene can be transmitted to other bacteria or organisms through horizontal or vertical gene transfer. Consequently, the whole population might be contaminated by antibiotic-resistant genes or bacteria in the aquaculture environment (Ruzauskas et al., 2018; Preena et al., 2020).

Risks assessment

Ecological risk of antibiotics

Antibiotic residues in aquaculture environment may have several adverse ecological impacts. Generally, researchers evaluate the ecological impacts based on measured or predicted concentration of antibiotics in the environment. However, it might be underestimated because significant amount of applied antibiotics is degraded through hydrolysis, photooxidation, and/or microbial action in aquatic environments and some antibiotics are accumulated in aquatic organisms.

For example, ofloxacin and doxycycline were found to pose definite ecological risk to algal population, whereas sulfonamides did not pose a significant ecological risk to the tested aquatic organisms. In China, the ecological risk for ciprofloxacin, erythromycin, enrofloxacin, ofloxacin, and tetracycline was determined and showed medium to high risks to algae and bacteria in aquatic ecosystem (Chen et al., 2021).

Resistance risk of antibiotics

Apart from ecological risk of antibiotics in aquaculture, antibiotic resistance risk in the environment is of recent major concern for the scientists. A new approach has recently been applied for the antibiotic’s resistance risk assessment by the following equation.

PNEC for resistance selection means that resistance is acquired when the concentration is higher than the value. In aquaculture, using the resistance data, some previous studies assessed the resistance risk of antibiotics by following the above equation (Bengtsson-Palme and Larsson, 2016).

The existence of residual antibiotics in the aquatic environment might facilitate the development of antibiotic resistance, thus enhancing the environmental risks of antibiotic resistance (Chen et al, 2021). The observed and size-adjusted minimum inhibitory concentrations (MIC) of antibiotics and PNECs for resistance selection are presented in Table 1.

Human health risk of antibiotics

Antibiotics are often misused and overused in livestock rearing and aquaculture farming, which might increase the antibiotic residues in food items (Liu and Wong, 2013). Lulijwa et al. (2020) reported the concentration of 14 antibiotics detected in fish and shellfish exceeded the country specific MRL guidelines.

The maximum residue limit exceeded in many countries is showed in Figure 3.

Recently, the antibiotic resistances in aquaculture products have also shown a major health concern issue worldwide. The presence of antibiotics in aquaculture environment might speed up the development of resistant genes of bacteria strains, which may eventually transfer to humans through food chains. Chen et al. (2017) have just used in their study of the maximum residue limit for several antibiotics by following different guidelines of Japan, Brazil, Chile, FDA, and China (Table 2).

However, many antibiotics are yet not to be decided for their residual levels in fish muscle or skin. In addition, combine/additive concentrations of antibiotics in fish muscle or skin are not considered in the current regulation worldwide.

Current antibiotic policy orientation and regulatory frameworks

The application of antibiotics in aquaculture is highly regulated in developed countries. Regarding present policies, the Food and Drug Administration (FDA), European Medicines Agency (EMA), the European Commission (EC), the Norwegian Food Safety Authority (NFSA), Codex Alimentarius Commission (Codex), and ministries of each country play the vital roles where EU, FDA policies, and regulations are widely used.

“The antibiotics such as florfenicol, oxytetracycline, sulfamerazine, and sulfadimethoxine-ormetoprim are authorized by the FDA for aquaculture use.”

The Norwegian veterinary medicine (VMP) wholesalers and feed mills are instructed to report their sales to pharmacies and fish farmers to the Norwegian Public Health Institute (NPHI). In the last decade, the use of antibiotics in producing salmon reduced from 1.0 to 0.36 mg/ kg fish production in 2014.

As a consequence, there was a very low probability of development of antibiotic resistance in Norwegian aquaculture and the transmission of such resistance to humans.

Suggestions for current policies and future thinking

Some approaches should be adopted globally on an immediate basis. Firstly, registration of aquaculture antibiotics must be obligatory in every country, and the limits of antibiotic use in aquaculture might be established.

Moreover, the use of important and critically important antibiotics (WHO categorized) particularly human antibiotics should be prohibited to use in aquaculture since many countries have already started to use the last-resort antibiotics against bacterial infections. Furthermore, international scientists need to take alternative initiative to limit the development and spread of bacterial infections and bacterial resistances in aquaculture.

Finally, new technologies and/or management strategies should exert emphasis on the minimization of antibiotic use to protect the aquaculture environments and to confirm the safety of consumers as
well as farmers.

Specific future thinking for the achievement of sustainable aquaculture production can be mentioned as follows:

– Development of effective vaccines, immune stimulants, or phage therapy alternatives to antibiotics to fight against diseases.

– Introduction of nutritious feed for the betterment of aqua-husbandry and maintaining of water quality in aquaculture industry, specifically in developing countries.

– Proper education and training are essential for the sensible use of antibiotics to the aquaculture sectors worldwide.

– Implementation of Norwegian model, which requires professional’s prescription to buy antibiotics in major aquaculture producers particularly in Asian and South American countries.

– Improvement of farm support for the proper diagnosis and treatment of diseases.

– Making country-specific antibiotic usage and antimicrobial resistance data bank and insure it is accessible to all.

– Finally, emphasis on research, collaboration, harmonization of policies, regulations, and sharing information in regional and international bodies are extremely needed.

Conclusions

This review encompasses the present status of antibiotic use in aquaculture and their probable ecological, resistance, and human health risks and importantly current policy and regulatory frameworks and future concerns.

Major aquaculture-producing countries such as China, Vietnam, India, Thailand, and Bangladesh are most likely using the elevated number of antibiotics in aquaculture. However, some of them have no stringent policy and regulatory frameworks or not strictly apply the regulations.

In addition, the maximum residue limits of antibiotics in fish/shellfish muscle in different countries gathered through many antibiotics are not yet to be decided. Also, combined concentration of antibiotics in fish muscle is not considered in the current regulations worldwide.

The main focus of this review is to develop a uniform regulation particularly for developing countries and to maintain the proper doses and number of antibiotic use in aquaculture for the production of safe, secure, and sustainable aqua-products.

Finally, it is suggested to make a country-specific data bank of antibiotic usage, their doses, withdrawal period, and most importantly antibiotic resistance data bank for better management and to achieve sustainable aquaculture production in the future.

This is a summarized version developed by the editorial team of Aquaculture Magazine based on the review article titled “ANTIBIOTICS, ANTIBIOTIC‑RESISTANT BACTERIA, AND RESISTANCE GENES IN AQUACULTURE: RISKS, CURRENT CONCERN, AND FUTURE THINKING”
developed by ANWAR HOSSAIN – University of Dhaka, ICHIRO NAGANO-Nissui, MD HABIBULLAH AL MAMUN -Southern Illinois University Carbondale, SHIGEKI MASUNAGA-Yokohama National University.
The original article was published in Environmental Science and Pollution Research, February 2022.
The full version can be accessed freely online through this link: https://doi.org/10.1007/s11356-021-17825-4.