Antimicrobial Resistance: Part #4 - Antimicrobials in Plants

Perhaps a more optimistic start to our antimicrobial resistance (AMR) series: the annual amount of antibiotics used for treating crops is relatively low compared to the amount used in livestock production, comprising only 0.36% of total antibiotic consumption in the agricultural industry (Smalla and Tiedje, 2014). This is because there are only a relatively small amount of bacterial diseases so difficult to control, antibiotics are required to compensate for the crops’ lack of natural resistance to these diseases (FAO, 2018a; McManus, 2014). It is due to this reason that antibiotic use on crops fell out of the limelight when it comes to major efforts to reduce its usage in the agri-food industry.

Nevertheless, there remain some areas of concern. In pre-harvests, antibiotics are largely administered to plants in the form of fine mists (Zhang et al., 2017). Indirect application could also still happen via the use of soil, organic fertiliser, e.g. manure, and irrigation water already contaminated with AMR bacteria (FAO, 2018b). Unfortunately, the full effects of how antibiotics interact through these methods are complex and still relatively understudied. Antibiotics applied via the usual air blast sprays to trees planted in an orchard system, for example, were found to not always reach their intended targets since sprays may drift or become lost by runoff due to external events such as rain, thereby complicating studies (Raman et al., 2020).

Pathways of antimicrobial agents (AMA) and AMR dissemination. Movement of AMA or AMR is indicated by the overlapping circles and arrows, while colours denote group reservoirs. Stars represent AMR genes and bacteria hotspots. Asterisks represent possible AMR genes and bacteria hotspots (Thanner, Drissner, and Walsh, 2016).

Data on antibiotics in the context of plant agriculture is scarce, even more so than its aquaculture counterpart. Global estimates on the antibiotic use is virtually non-existent, and the full effects of said use, including how consuming crops contributes to the spread of antibiotic AMR genes, has yet to be fully understood. Fortunately, there is gradually mounting evidence of the potentially adverse effects on public health and the environment: vegetables grown conventionally and organically to be consumed raw facilitate the spread of AMR genes (van Hoek et al., 2015); AMR bacteria transmitted from plants to humans could asymptomatically “colonise” the intestines for an extended period of time before being discharged from the body (Maeusli et al., 2020); already contaminated crops grown as feed introduces AMR genes into the animals fed with these crops, thus accelerating the spread of AMR genes into the food chain (Marshall and Levy, 2011).

This is the fourth article of a multi-part series on the topic of antimicrobial use in the agri-food sector by Khor Reports. Read the previous posts here: Antimicrobial Resistance: Part #1 - The General Gist; Antimicrobial Resistance: Part #2 - Antimicrobials in Livestock; Antimicrobial Resistance: Part #3 - Antimicrobials in Aquaculture.

Antimicrobial Resistance: Part #3 - Antimicrobials in Aquaculture

Next up on our antimicrobial resistance (AMR) series: antimicrobials in aquaculture. Similar to livestock production, antimicrobials are used in fish farms to treat and prevent diseases, and are commonly administered via water medication and medicated feed. While these methods do encourage the development of AMR, they are not its only source—the use of organic fertilisers, such as farm animal wastes, also contribute toward AMR, especially if the waste was from livestock already extensively fed with antimicrobial agents (Aly and Albutt, 2014).

Aquaculture production has surpassed wild catch since 2012, with an average person now consuming almost double the amount of seafood compared to the past 50 years (Ritchie, 2019).

More crucially, while the use of antibiotics in aquaculture remains the same as their livestock counterpart, the dosage administered in the former can be much higher proportionally compared to the latter (O’Neill, 2015). This, combined with the fact that antibiotics can remain within the aquatic environment for an extended period of time—there is evidence to suggest that 70 to 80% of antibiotics fed to fish are excreted into the water (Cabello et al., 2013; Burridge et al., 2010)—has led to experts dubbing aquaculture sites as “reservoirs” and “hotspots” for AMR genes (Van et al., 2020; Watts et al., 2017; Muziasari et al., 2016).

The situation is further aggravated by the rapidly growing practice of aquaculture itself—since the stress of industrial-scale farming compromises the fish’s immune system, it justifies the widespread use of antibiotics as a way to compensate for the fish’s increased vulnerability to infections and diseases (Meek, Vyas, and Piddock, 2015). A recent study between CIRAD and French National Research Institute for Development has also shown global warming may even promote the use of antibiotics, particularly in the low- and middle-income countries—warmer temperatures almost always result in higher mortality rates of fish, which could lead to an increased use of antibiotics (Reverter et al., 2020).

Unsurprisingly, the development of AMR in aquaculture production (as with any other agri-food industries where antibiotics are used) adversely has devastating affects on the environment and public health, typically in the form of superbugs, i.e. bacteria that should have been killed by antibiotics, but instead evolved to become stronger. Yet, overall data on the amount of antibiotics used in aquaculture and how much of it is absorbed into the aquatic surroundings is still far from satisfactory. Approximately 90% of global aquaculture production is carried out in countries where regulations on antimicrobial use are either lax or non-existent, resulting in data that varies greatly from nation to nation (Watts et al., 2017).

The figure above depicts the global multi-antibiotic resistance (MAR) index calculated from aquaculture-derived bacteria. An MAR index of 0.2 indicates a high-risk of antibiotic contamination. The mean global MAR index is 0.25. 28 countries out of the 40 selected for study displayed an index of higher than 0.2 (Reverter et al., 2020).

Nonetheless, there is evidence to suggest that antibiotic use is dependant on a country’s regulations and legislation on the same. For example, in Chile, where there have been resistance from some aquaculture companies against the government’s attempts to regulate antibiotic use, approximately 300 tonnes of antibiotics is used every year in the aquaculture industry. As a comparison, Norway imposed stringent legislation on antibiotic use in aquaculture (and largely replaced with more sustainable alternatives such as vaccines) and now relies on only one tonne per annum (FAO, accessed June 2020).

There is some sliver of hope, however. Some companies are beginning to respond to the growing concern on the impacts of antibiotic use. Chilean-based Marine Harvest, one the largest marine farming enterprise in the world, has pledged to slash its antibiotic use from 450gm per metric tonne of harvested salmon to 150gm per metric tonne. Lerøy Seafood Group from Norway has stopped using antibiotics in their fish farms since 2017 (although it should be noted that as mentioned before, Norway as a whole had already enforced strict monitoring of the antibiotics use, which included measures such as a traceability system that tracks the health and harvesting details of fish products). Nevertheless, experts widely agree that much more needs to be done.

This is the third article of a multi-part series on the topic of antimicrobial use in the agri-food sector by Khor Reports. Read the previous posts here: Antimicrobial Resistance: Part #1 - The General Gist; Antimicrobial Resistance: Part #2 - Antimicrobials in Livestock.

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In separate news, a newly found cluster of coronavirus cases from the Xinfadi meat market in Beijing recently triggered a consumer panic after traces of the virus were found on a chopping board used to cut up imported salmon. The discovery prompted China to temporarily stop salmon imports into the country as numerous eateries and supermarkets began pulling foreign fish and meat products from their menus and shelves.

In response to this incident, the Norwegian Food Safety Authority and Norwegian Seafood Council stressed that there are no cases of coronavirus infections spreading via contaminated food. This claim was later backed by the China Center for Disease Control and Prevention, who further clarified that there is currently no evidence to suggest that salmon itself could host the said virus.

Antimicrobial Resistance: Part #2 - Antimicrobials in Livestock

As mentioned in our previous article on antimicrobial resistance (AMR), antimicrobials are typically used in the livestock production to treat sick animals, to prevent future disease from spreading amongst livestock, and to stimulate growth, usually via the feed and water provided to the animals.

Since any and all uses of antimicrobials contribute towards the development of AMR, it is important that their use is limited to only when it is medically necessary. Unfortunately, statistics reveal a less-than-stellar practice at work—it is estimated that global antimicrobial consumption by food animals in 2013 was 131,109 tonnes (Van Boeckel et al., 2017), a whopping increase of 107% from the conservatively estimated 63,151 tonnes in 2010; Center for Disease Dynamics, Economics & Policy (CDDEP) projections further reveal a potential increase in consumption by more than half by 2030.

The CDDEP has developed an interactive ResistanceMap which helpfully shows the estimated consumption of antimicrobials in 2013 and projected change of the same in 2030 for each nation. Also featured in the map are the AMR (exposure) of chickens, pigs, and cattle.

Note: PCU, i.e. population correction unit, is a standardised theoretical unit developed by the European Medicines Agency which allows for YOY comparisons. 1 PCU = 1kg, e.g. 319mg/PCU in mainland China would mean that on average throughout 2013, 319mg of antibiotics was used for every kilogramme of body weight of a livestock at the time of treatment (United Kingdom Veterinary Medicines Directorate, 2016).

An article by Van Boeckel et al. (2015), which was cited over 1,200 times according to Google Scholar, reported that in 2010, the countries recording the biggest shares of global antimicrobial consumption by livestock were China (23%), the United States (13%), Brazil (9%), India (3%), and Germany (3%); by 2030, this ranking is expected to change to China (30%), the United States (10%), Brazil (8%), India (4%), and Mexico (2%). The graph below showcases further rankings of countries by largest increase and largest relative increase in antimicrobial consumption between 2010 and 2030.

(It is interesting to note here that livestock in China and Brazil, despite being the top consumers of antimicrobials, did not count amongst the countries with the most rapid projected increase in consumption. Van Boeckel et al. (2015) suggest that this implies that the two nations have already shifted toward intensified livestock production systems, where antimicrobials are regularly used to maintain the health and productivity of the animals.)

Van Boeckel et al. (2015): (A) Largest five consumers of antimicrobials in livestock in 2010. (B) Largest five consumers of antimicrobials in livestock in 2030 (projected). (C) Largest increase in antimicrobial consumption between 2010 and 2030. (D) Largest relative increase in antimicrobial consumption between 2010 and 2030. CHN, China; USA, United States; BRA, Brazil; DEU, Germany; IND, India; MEX, Mexico; IDN, Indonesia; MMR, Myanmar; NGA, Nigeria; PER, Peru; PHL, Philippines.

Van Boeckel et al. (2015): Antimicrobial consumption in chickens (A) and pigs (B) in 2010. Purple indicates new areas where antimicrobial consumption will exceed 30 kg per 10 km2 by 2030.

The increase in antimicrobial consumption has been attributed towards the growing global demand for meat (FAO, 2017; Van Boeckel et al., 2017; Gelband et al., 2015). This trend is clearly observed in countries within the Asian region, where regulations on antimicrobial use are still lax or in its infancy (Lo et al., 2019). Antimicrobial consumption by livestock in Asia alone is estimated to be 51,851 tonnes by 2030, with chicken and pigs expected to consume an increase of 129% and 125% of antimicrobial respectively by 2030 (Van Boeckel et al., 2015).

Consumers, particularly those in higher-income nations, however, are growing increasingly, albeit slowly, becoming aware of AMR and its adverse effects on human health. The total sales of antibiotic-free chicken in the United States, for example, increased by 34% in 2012 with a Consumer Reports survey in the same year reporting that more than 60% of respondents are willing to pay an extra five cents per pound for antibiotic-free meat.

Food producers are still slow on the uptake, unfortunately. In 2019, it was found that most fast-food chains in the US, including big names such as Burger King, Pizza Hut, Domino’s Pizza, and Chilli’s, still do not have policies or plans in place to reduce antibiotic use in their beef supply. This is worrying, especially since factory farming has been linked to the emergence of antibiotic resistant superbugs, which constitutes a serious threat to human health. In response, famed primatologist and conservationist Jane Goodall has warned that there is not much time left to “change our ways… [and] drastically change our diets and move to plant-rich foods”.

This is the second article of a multi-part series on the topic of antimicrobial use in the agri-food sector by Khor Reports. Read the first post here: Antimicrobial Resistance: Part #1 - The General Gist.

Antimicrobial Resistance: Part #1 - The General Gist

There is a growing danger as big as, but lesser known than, the looming threat of climate change: antimicrobial resistance (AMR). Defined by the Food and Agricultural Organisation of the United Nations (FAO) as “micro-organisms—bacteria, fungi, viruses, and parasites—[evolving] resistance to antimicrobial substances, like antibiotics”, AMR adversely affects food safety and security by rendering medicines much less effective or useless when it comes to treating infections. While it is difficult to quantify the full economic and health impact of AMR, the FAO estimates that global GDP will decrease by 2 to 3.5%, equivalent to USD100 trillion, by 2050, with up to 10 million human lives lost each year.

Generally, antimicrobials in agriculture are used by farmers in the livestock production and fish farming industries to treat sick animals, to prevent future disease from spreading amongst livestock, and to stimulate growth, usually via the feed and water provided to the animals. In plant agriculture, antibiotics are usually sprayed onto plants as a fine mist, although direct antibiotic application on crops is much more modest compared to its use in livestock (McManus et al., 2002); however, it should be kept in mind that indirect applications could still happen via the use of manure and wastewater already contaminated (Zhang et al., 2017).

The amount of animal consumption of antibiotics is rather eye-opening—in the United States throughout 2012 alone, 72.5% of the use of medically important antibiotics were found to have been for animals, with only 27.5% used by humans; in absolute figures, animal consumption of antibiotics was 8.9 million kg compared to human consumption of 3.4 million kg (FDA, 2012; IMS Health, 2012).

“When we have a flock and there’s a lot of sick chickens in that flock, the quickest way to get an antibiotic in them is to put it in the water. We do that through a system that proportions that water out uniformly through all of these water lines so that every drink, every drop has the correct amount of antibiotics.”

The same practices were later adopted in aquaculture, the difference being that antibiotic doses may be proportionally higher than doses in livestock (O’Neill, 2015). Residue from antimicrobials as well as undigested food and faeces containing unabsobed antimicrobials usually remain in the water and the surrounding sediments for an extended amount of time, with some studies further suggesting that 70 to 80% of antibiotics administered to fish are excreted into the water (Cabello et al., 2013; Burridge et al., 2010).

Pathways of AMR genes from closed and open aquaculture systems into the water and its surrounding environment (Watts et al., 2017).

In comparison, the antibiotic use for crops is relatively low, comprising only 0.36% of total agricultural antibiotic consumption (Smalla and Tiedje, 2014). While this resulted in much less attention given to antibiotic use in plants, the potentially extensive use of fungicide may be a source of concern since fungal diseases presents significant threat to crops (O’Neill, 2015).

It is quite undeniable that the issue of AMR is an increasingly alarming one. With news of bacteria developing new resistance to antibiotics and increasing resistance in animals such as dolphins, it is clear that, quoting author and journalist Maryn McKenna in her book Big Chicken, AMR is becoming “an overwhelming threat, created over decades by millions of individual decisions and reinforced by the actions of industries.” It would be interesting to see further developments in this area.

This is the first article of a multi-part series on the topic of antimicrobial use in the agri-food sector by Khor Reports.