Investors in meat companies do not usually fret about microbes, but in the midst of a pandemic such worries have become more commonplace.

Of mounting concern is not just the virus that causes COVID-19, but also the meat industry's longstanding dependence on antibiotic use in farm animals to prevent disease and speed up growth — one big reason why resistance is spreading across the globe and rendering many vital, lifesaving drugs useless. In the U.S., partly because of antibiotic use, the average market weight of broiler chickens jumped from about 2.5 pounds in 1930 to 6.2 pounds in 2015, according to the National Chicken Council. Plumper birds offer more revenue for poultry farmers, but that growth is also contributing to a global health emergency.

Antimicrobial resistance, or AMR, has made several deadly ailments such as tuberculosis, pneumonia and kidney infections harder to treat while undermining patient outcomes for hip replacements, cancer therapy and cesarean sections. About 700,000 people worldwide die each year from AMR complications. If resistance is not tackled, the U.K. government warns that the annual death toll will hit 10 million by 2050 and knock $100 trillion from global output. A World Bank report estimates that by 2050, annual global GDP would fall anywhere from 1.1% to 3.8% as a result of drug-resistant infections and cause economic havoc on the scale of the 2008 financial crisis.

"It is an enormous, systemic market failure," said Abigail Herron, global head of responsible investment at Aviva Investors, in an interview. "AMR doesn't have the same pedigree as palm oil or human rights ... but we want investors to take it seriously and bump it up the ESG agenda." If the investor push works, it could force a shift in longstanding meat production methods and add sizable costs to a supply chain already weakened by the pandemic.

The pressure started to build before COVID-19 hit. In recent years, nonprofit groups and investors persuaded most of America's top 25 fast-food chains, including McDonald's Corp., The Wendy's Co. and Doctor's Associates Inc.-owned Subway, to serve only chicken raised without the help of medically important antibiotics. By 2018, 92% of U.S. broiler chickens were raised without such antibiotics.

"It was a huge victory," said Christy Spees, environmental health program manager at As You Sow, a California-based shareholder advocacy group, in an interview. "It's the combination of pressures that worked."

That pressure now is set to intensify as restaurants, investors, regulators and consumers push big meat producers to cut antibiotic use across more protein groups, especially beef, pork and turkey. Despite progress on chicken, in the U.S. about two-thirds of antibiotics deemed important for human health continue to be given to food-producing animals, according to Food and Drug Administration data.

Tesco PLC and Marks & Spencer Group PLC of the U.K. already are demanding better "antibiotics stewardship" from meat suppliers. Whole Foods, a unit of Amazon.com Inc., has a strict "no antibiotics" policy. One of the biggest beef buyers in the world, McDonald's, has pledged to measure the use of antibiotics in its 10 biggest markets and set targets to curb their use by the end of 2020. Costco Wholesale Corp. says that by the end of 2020 it will "assess the feasibility of eliminating the routine use of medically important antibiotics for prevention of disease among supplier farms."

BMO Global Asset Management, with $273 billion under management, recently pressed 38 companies on their antibiotic use, including Tyson Foods Inc., Hormel Foods Corp., Brazil's BRF SA and the Inner Mongolia Yili Industrial Group Co. Ltd., the biggest dairy company in China, the country that is the largest user of animal antibiotics.

"We want companies to phase out antibiotics for routine use, and definitely for growth promotion," said Catherine McCabe, senior associate analyst at BMO, in an interview.

At the World Economic Forum in Davos in January 2020, the U.K. Department of Health and other groups launched an initiative called "Investor year of action on AMR" to recruit asset managers and pension funds and escalate the anti-antibiotics drive. Although the pandemic has disrupted their planned year of action, the time frame has been extended.

On its website, JBS SA of Brazil says its U.S. operations use antibiotics only for "controlling or treating disease, rather than growth promotion or feed efficiency." Similarly, closely held Cargill Inc. maintains that it supports "the responsible use of human antibiotics in food production" and isn't using any antibiotics vital to human medicine.

Tyson says all chickens for its own-name retail brand now are raised without antibiotics. "Tyson Foods is the world's largest producer of no-antibiotics-ever chicken," a spokeswoman for Tyson said in an emailed comment. The company also "markets beef and pork under the Open Prairie natural brand produced from cattle and pigs raised without antibiotics."

The broader picture is less sanguine. In November, the investor network Farm Animal Investment Risk and Return, whose members collectively have $25 trillion under management, published a report showing that 65% of 60 of the biggest publicly traded protein producers did not disclose data on antibiotic use. In addition, 42 of those companies, with a collective market capitalization of $244 billion, ranked as "high risk" for antibiotic stewardship, including all beef and dairy producers.

Another assessment published by the Natural Resources Defense Council and several other nonprofit groups in October 2019 noted that in 2017, cattle accounted for 42% of all medically important antibiotics sales to the U.S. livestock industry, more than any other category. Of the top 21 U.S. restaurant chains that serve beef, 15 received failing grades on antibiotic use for not taking action beyond compliance with FDA requirements. "The contrast between chain restaurant policies on antibiotic use in the chicken versus the beef they serve is stark," concluded the report, called Chain Reaction V.

Globally, the challenge is the sheer scale of demand for meat. With producers in China, India, South Africa and Brazil using more antibiotics than ever, the worldwide consumption of antibiotics in agriculture is set to jump 67% from 2010 to 2030, according to the World Bank. Of the 27 different antibiotic classes used to promote growth in livestock, 18 are drugs used to treat people, such as tetracycline.

In the U.S., sales of antibiotics for food-producing animals rose 24% between 2009 and the peak year of 2015, fell back in 2016 and 2017, then rose 9% between 2017 and 2018, according to the most recent data published by the FDA. It is unclear what drove the recent increase.

Modern meat production methods can amplify drug resistance. Resistance emerges when bacteria undergo genetic changes that make them immune to existing drugs. When animals are slaughtered and processed, germs in their gut, including resistant bacteria, can contaminate the meat and sicken people who eat it. Animal waste also can harbor traces of consumed antibiotics and resistant bacteria. When the waste is used as fertilizer, resistant bacteria have another route to enter the wider environment.

A few years ago, researchers Cindy Liu and Lance Price of George Washington University conducted a study in Flagstaff, Ariz. Over 12 months they isolated bacteria from hundreds of supermarket chicken samples and also isolated bacteria from blood and urine samples of locally hospitalized patients. Their findings confirmed what other scientists had long feared: that antibiotic-resistant E. coli bacteria, which can cause harmful urinary tract and kidney infections, could originate on farms and move to people.

"The likely link between foodborne E. coli and human urinary tract infections underscores the public health relevance of the use of antibiotics in food animal production," the authors wrote in their 2018 study, published in the microbiology journal mBIO.

The pandemic appears to be exacerbating the problem of antibiotic overuse. A multicenter U.S. study found that 6.9% of hospitalized COVID-19 patients acquired a secondary bacterial infection, yet 72% of them received antibiotics even when their use was not clinically indicated, according to research published in the journal Clinical Microbiology and Infection in July.

"COVID-19 is fueling a huge increase in the use of antibiotics in hospitals, and concern about antimicrobial resistance is accelerating," said McCabe of BMO.

In a presentation to an AMR conference in August, Matt Crossman, stewardship director of Rathbone Investment Management, said: "More and more engagement on AMR from the investor community is desperately needed not in spite of, but because of, the pandemic we are experiencing."

READ MORE: Sign up for our weekly coronavirus newsletter here, and read our latest coverage on the crisis here.

Consumers, meanwhile, are fighting antibiotic use by demanding more organic meat and meat substitutes. The demand for organic meat is forecast to grow from $14.38 billion in 2019 to $20.39 billion in 2023, according to research firm Statista. Sales of plant-based meat are projected to grow from less than 1% of all meat sales today to $50 billion, or 4% of all meat sales, by 2025, says UBS.

There is pressure from regulators too. In 2018, then-FDA commissioner Scott Gottlieb launched a plan to promote the "judicious use" of antibiotics in animal agriculture and veterinary settings between 2019 and 2023. The European Union has been more aggressive, banning routine antibiotic use in animals from 2022 onwards. In July 2019, India forbade farmers from using colistin, a "last resort" weapon against multidrug-resistant infections in people.

When meat producers are forced to significantly taper antibiotic use, the health benefits can be noteworthy.

In November 2015, Chinese researchers announced their discovery of MCR-1, a gene that can make dangerous bacteria immune to the vital antibiotic colistin. The finding sent shockwaves through the medical community. Less than six months later, the gene was found in a patient in Pennsylvania. It eventually spread to more than 40 countries.

"The Chinese findings, which have been replicated in several other countries, solidify the links between the agricultural use of antibiotics, resistance in slaughtered animals, resistance in food, and resistance in humans," said Margaret Chan, then-director general of the World Health Organization, in 2016. "This is a crisis, and it is global."

In April 2017, alarmed authorities in China banned colistin as a growth promoter in animal feed. Three years later, in June 2020, another team of researchers published a study in the journal The Lancet Infectious Diseases assessing the ban's impact.

The ban has had "a significant effect on reducing colistin resistance in both animals and humans in China," they wrote. The positive outcome, they added, was "a crucial step in preserving this essential antibiotic for human medicine."