Antibiotic Resistance and Animal Protein Business: Historical Background, Regulatory Evolution and Market Responses

by Dr. Paolo Doncecchi, DVM

1. Antibiotic resistance: an ancient biological phenomenon

Antibiotic resistance must be set in a very long prospect.

Several studies are published in the last few years have shown demonstrated that the antibiotic resistance already appeared in the very first appearance of our species, as from some 300.000 years ago (both Neanderthal and Sapiens) [1]: in fossils dental calculus, there were found “Antibiotic Resistance Determinants” (ARDs) able to develop resistance againt the natural “antibiotics” developed by the individuals of those Homo species.

So, the fight between the human beings and the bacteria is a fight coming from the very long past, even considering that bacteria appeared in our planet some 3.5 billion years ago; in a future article, we will detail the other biological entities which fought bacteria from the very beginning, indeed (like bacteriophages).

2. The modern antibiotic era and its medical breakthrough

Returning to the more recent history of medicine, antibiotics represented a real breakthrough in fighting critical, deadly bacterial diseases, helping to improve human welfare alongside improvements in hygiene and nutrition quality.

3. From therapeutic success to antimicrobial resistance burden

Modern antibiotic therapy began with the first commercialized sulfonamide in the 1930s, followed by penicillin in the 1950s and the tetracycline family in the early 1960s. Antibiotic resistance started to become evident with the global use of these three classes of antibiotics.

The pharmaceutical industry reacted by discovering new families of antibiotics or combinations of these drugs, which faced newly created bacterial resistance. Consequently, over the last 20 years, antimicrobial resistance (AMR) has become a social and economic burden, prompting public and private stakeholders to take active measures to combat it.

Foremost among public stakeholders is the World Health Organization (WHO), which publishes an annual document titled the "Global antibiotic resistance surveillance report." The report[2] provides adjusted global and regional estimates of AMR for 2023 across 93 infection type–pathogen–antibiotic combinations, presents adjusted national AMR estimates for 2023 for key pathogen–antibiotic combinations, and tracks global and regional resistance trends for 16 combinations between 2018 and 2023 using data from human consumption across more than 100 countries.  

The WHO publishes numerous guidelines and documents related to AMR. Of particular interest is the document shown below: the figure highlights that excessive antibiotic use in livestock and fish farming is one of the major drivers of resistance, linking the global AMR issue directly to animal protein production, as it demonstrates that the "over-use of antibiotic in livestock and fishing farming" is among the six key sources of resistance.

3.1. Antimicrobial resistance as a global health and economic threat

Many other public stakeholders focus their attention over AMR [3].

This burden is well indicated by this table below, produced by United Nations Environment Programme.

The original graph was published in 2016 by UK government.

It shows that if there is not a global intervention against AMR, in 2050 this could generate very high rate of mortality, higher than cancer and diabetes.

This comparison frames AMR not only as a clinical issue but also as a long-term public health and economic threat requiring coordinated intervention.

This historical and medical context leads directly to a second question: how antibiotic use in animal protein production has contributed to the broader AMR burden and how regulation has progressively responded.

4. Use of antibiotics in livestock production

Antibiotic use in animal protein production began in the early 1960s with the registration of the same three categories of antibiotics used in human medicine. From the late 1970s through the first decade of this century, other categories of antibiotics—such as macrolides, cephalosporins, and polymyxins—were registered and launched, and resistance appeared as quickly as it did in human medicine.

First reaction in key livestock Countries throughout the world has been to tighten registration process, demanding exact definition of withdrawal time [4] and MRL [5].

5. Public regulation and progressive restrictions

As from early '90s, with the rise of the antibiotic resistance burden, public stakeholder started to increase the level of attention around this antibiotic use:

• in many countries or in some regions, a ban was decided vs. some specific antibiotics or category of antibiotics

• the first category was the AGP (Antibiotic Growth Promoters): first Denmark, than Europe the ban was total; in the rest of the world the (partial) ban arrived not in an uniform way: complete, like In New Zealand, partial in Brazil (only for the poultry meat exported in Europe), etc.

• again in Europe, some Countries (Denmark, Sweden, Benelux in different years in the '90s) banned macrolides, fluoroquinolones and cephalosporins of 3rd and 4th generation.

Then, in 2019, Europe (through their regulatory bodies EMA/CVMP [6]) published a EU Directive [7] to ban all prophylactic and metaphylactic use of all antibiotics in animal production by Jan 2022.

5.1. Restrictions on critically important antibiotics

Overlapping or anticipating these EU decisions, the WHO—followed by the EMA—established categories of importance designating certain antibiotics exclusively for human medicine. Third- and 4th-generation cephalosporins, macrolides, and polymyxins are considered of high importance and are dedicated solely to human treatments to avoid any kind of cross-resistance resulting from animal protein consumption.

Today, these molecules see very limited livestock use, permitted only under specific circumstances where a certified laboratory confirms the necessity through an antibiogram.

6. Private sector initiatives and market pressure

Further adding to all these public stakeholder activities, we must indicate indeed the activity of some specific private stakeholders which further push to reduced consumption of antibiotics, at least in some specific sector.

One example is McDonald [8] which aims by 2030 to offer in their shops poultry meat from poultry farms using any antibiotic, included ionophores to control coccidiosis.

These farms are indicated as NAE (No Antibiotic Ever).

This decision has dramatically reduced antibiotic consumption in US poultry sector (poultry, layers and turkey).

In a 2025 publication of US Poultry and Egg Association has presented a report, covering the use of antibiotics from 2013 through 2024 for U.S. broiler chickens and turkeys and from 2016-2024 for U.S. layer chickens [9].

Results are shown below from the infographics published in the same report:

we present “only” the broiler data, leaving our reader to read the pdf for layers and turkey.

These figures demonstrate the scale of reduction achieved in U.S. poultry production while also highlighting the operational limits of strict NAE programs discussed below.

6.1. Limits of the NAE model and industry adjustment

However, in 2024 and 2025, some integrated poultry groups abandoned the NAE approach for broilers because they could not consistently meet consumer demand for NAE animal protein while maintaining animal health without any antibiotic use.

While antibiotic use in broilers decreased significantly, the use of penicillin and lincomycin increased between 2019 and 2023 due to a resurgence of gangrenous dermatitis caused by Clostridium septicum and Clostridium perfringens.

Other reasons cited for discontinuing NAE practices include:

• Animal welfare management: NAE poultry production requires rigorous rearing practices, such as lower stocking densities, consistent feed quality, and longer downtimes between production cycles.

• Supply chain management: Consistently supplying NAE poultry protein has become a significant challenge across the entire supply chain.

• Animal health management: Challenges include gangrenous dermatitis and a resurgence of coccidiosis (since the NAE approach does not involve ionophore coccidiostats).

Industry response:

• Abandoning "NAE" labels to adopt the "NAIHM" (No Antibiotics Important to Human Medicine) label.

• This approach allows the use of antibiotics intended exclusively for veterinary use when necessary for animal care.

7. Current trends and outlook to 2050

A recent study co-authored by several FAO researchers [10] has elaborated a scientific method to project antibiotic consumption in all world Regions till 2040. we show here 2 key graphics of this paper.

In the first graphic, Authors present projected global antimicrobial usage quantity (AMUQ) in tonnes for livestock under a BAU (Business as Usual) scenario from 2000 to 2040. The solid blue line represents the projected AMUQ trend, while the dashed lines and error bars indicate the 95% confidence intervals over the projection period.

The projected increase under the business-as-usual scenario shows why reduction strategies must address both the intensity of antibiotic use and the growth of livestock biomass.

In the second graphic, Authors project regional livestock AMUQ by 2040 with 95% confidence intervals (CI) (in tonnes): this figure presents the projected AMUQ in livestock, in 5 global Regions by 2040. The projections include 95% (error bars) to indicate the level of uncertainty in the estimates.

The regional projection reinforces that future antimicrobial use will not evolve uniformly across regions, making local policy design and monitoring essential.

The synthesis written in the abstract states that:

“This study projects global livestock antibiotic use quantities through 2040 under various scenarios. This work indicates that under a business-as-usual scenario, global antibiotic use could reach ~143,481 tons by 2040, representing a 29.5% increase from the 2019 baseline of ~110,777 tons.

However, alternative scenarios suggest that these projections could vary by +14.2% to -56.8%, depending on changes in livestock biomass and antibiotic use intensity. A key contribution of this research is the development of the Livestock Biomass Conversion method, a novel indicator offering improved accuracy in estimating livestock biomass. The findings have important policy implications, highlighting that meaningful reductions in antibiotic use quantity can only be achieved through coordinated efforts targeting both antibiotic use intensity and livestock biomass”. [10]

7.1. European monitoring and reduction targets

European Authorities particularly the ESVAC [11] study collect antibiotic data consumption since in 2010 from 27 EU Contries, Iceland and Norway.

2024 data show a trend of reduction of 24% vs. 2010, calculated in terms of milligramme of antibiotics under PCU [12], corresponding to the graphic below.

The graphic is promising.

In the same time, the 2030 target aims to half the antibiotic consumption compared with 2018 (as mg/PCU).

8. Conclusion and next articles

Antibiotic resistance is one global health topic under scrutiny for all its economical and social implications.

Public and private stakeholders (global, regional and Country ones) have been rolling out policy to manage this burden.

Private stakeholders can indeed play a global role to contribute to the reduction of antibiotic (mis)use, offering the so-called ATA (Alternative to Antibiotics).

These ATA could contribute indeed to achieve Animal Resilience and eventually, Precision Livestock Farming (PLF).

Resilience, One Health Program, PLF, Consolidated ATAs and Innova Biotechnology ATAs will be in due order the topics of the next articles in the Academy section, inside Innovabiotechnology Internet site menu.

Bur before these topics, in the next article we will write again on AMR, focusing our attention on the recent concept of RESISTOME. 9. Notes and References

[1] Sankaranarayanan G, Muthukaliannan GK. Exploring antimicrobial resistance determinants in the Neanderthal microbiome. Microbiology Spectrum. 2024;12(8):e02662-23.

[2] World Health Organization. Global antibiotic resistance surveillance report 2025. Geneva: World Health Organization; 2025. The original article links this report to the WHO publication page.

[3] United Nations Environment Programme. Bracing for Superbugs: Strengthening environmental action in the One Health response to antimicrobial resistance. The original article links this source to the UNEP environmental-action resource.

[4] — Explanatory note: Withdrawal time

Distance in days or hours between last antibiotic administration and the consumption of the specific animal protein produced (meat, milk or eggs).

[5] — Explanatory note: MRL

Maximum Residue Limit: maximum amount of veterinary medicine residue that is legally allowed to remain in food products like meat, milk, eggs, honey. Set in by EMA in EU, FDA in US, Codex Alimentarius / WHO-FAO for international standard; without MRL, you cannot sell that drug for food-producing animals.

[6] — Explanatory note: EMA/CVMP

EMA: European Medicine Agency – CVMP: Committee for Veterinary Medicine Products.

[7] European Parliament, Council of the European Union. Regulation (EU) 2019/6 of the European Parliament and of the Council of 11 December 2018 on veterinary medicinal products and repealing Directive 2001/82/EC. Official Journal of the European Union. 2019. The original article provides the EUR-Lex link.

[8] McDonald's Corporation. Responsible antibiotic use [Internet]. The original article provides the McDonald's corporate source concerning responsible antibiotic use.

[9] U.S. Poultry & Egg Association. Antibiotic Stewardship Report 2025 [Internet]. Tucker (GA): U.S. Poultry & Egg Association; 2025. Available from: https://www.uspoultry.org/poultry-antibiotic-use-report/docs/USPOULTRY-AntibioticStewardshipReport-2025.pdf 

[10] Acosta A, et al. (2025). The original document identifies the source by DOI: 10.1038/s41467-025-56825-7.

[11] European Medicines Agency. European sales and use of antimicrobials for veterinary medicine: Annual surveillance report for 2024 [Internet]. The original document provides the EMA report URL.

[12] — Explanatory note: PCU

PCU is the name of the ESVAC denominator, with 1 PCU unit equivalent to 1 kg of animal biomass.

Author

Dr. Paolo Doncecchi, DVM

Chief Technology Officer

Innova Biotechnology Sp. z o.o., Warsaw, Poland