WAAW - Day Two: The risks of AMR

Ashwati Sarman, a Graduate Trainee at G&L, examines the detrimental impact of AMR on both human and animal health.

The significance of Antimicrobial Resistance (AMR) is increasingly acknowledged as a critical concern for both human and animal health.

Infectious diseases cause millions of human and animal illnesses and fatalities worldwide each year, and the number of ways to prevent and treat them is under severe pressure.

Modern antimicrobial drugs are in almost constant use to prevent and treat infections caused by microorganisms, encompassing bacteria, viruses, fungi, and microscopic parasites in humans, animals, and plants.

However, the efficacy of these antimicrobials is under extreme threat due to the emergence of drug-resistant pathogens, leading to AMR – so much so that the World Health Organization (WHO) has classified AMR as one of the top 10 global public health threats.

Understanding AMR

AMR is characterized by microorganisms' ability to thrive or survive in the presence of antimicrobials, like antibiotics, antifungals, antivirals, antimalarials, and anthelmintics, at concentrations that typically inhibit or kill these microorganisms.

AMR arises when microorganisms evolve to resist antimicrobials following repeated exposure to these drugs.

Consequently, these drugs lose their effectiveness against susceptible microorganisms, resulting in persistent infections, increased risks of severe illness or death, and the potential for disease transmission.

The efficacy of antimicrobial drugs can be lost through several molecular mechanisms that can lead to resistance.

Some are “intrinsic”, whereby the microorganism can use genes it already possesses to survive exposure to the antimicrobial, and some are “acquired”, whereby the microorganism gains new genetic material which, in turn, can provide capabilities that facilitate survival.[i]

The causes of AMR

Uncontrolled or irresponsible use of antimicrobials is the primary cause of AMR. The consequences of AMR include a reduced arsenal of drugs available for preventing, controlling, and treating even minor infections.

One notable impact is the rise in surgical site infections (SSI) in humans, which are the most common type of hospital-acquired infections.

The increased incidence of AMR has diminished the efficacy of standard antibiotics administered before surgery for SSI prophylaxis, leading to prolonged hospitalization, extended antibiotic treatments, surgical revisions, and increased mortality rates.

To mitigate SSI, it's vital to screen for antimicrobial resistance risks and select the most appropriate antimicrobial agents based on susceptibility. [ii]

Antibiotic-resistant bacteria with genetically modified resistance to antibiotics are becoming more prevalent, including resistance to multiple classes of antibiotics, termed multiple or pan resistance.[iii]

The impact on society

A study in the April 2023 edition of The Lancet Microbe[iv] underscores the societal impact of AMR.

The practice of adding antimicrobials to livestock water and feed, especially in intensive agriculture, has significantly contributed to antibiotic resistance. Antibiotics being given to herds or flocks of livestock where only a few animals show symptoms of infection is called antibiotic metaphylaxis.[v]

Efforts to restrict this practice have been slow, with some countries still allowing it. Notably, last-resort antibiotics like Colistin are added to animal feed, despite being designated as a treatment of last resort for Gram-negative infections by the WHO.

Research indicates that Colistin, an antibiotic of last resort, is introduced into animal feeds to facilitate both animal growth promotion and disease prevention². The WHO has singled out Colistin as a medication reserved for the treatment of severe Gram-negative infections, such as those triggered by E. coli.[vi]

Moreover, the research presented in the aforementioned Lancet Microbe article² revealed that specific strains of bacteria, extracted from animals, animal products, and patients, including E. coli, carry genetically altered genes that confer resistance to Colistin.

Regrettably, both livestock producers and the general public lack awareness regarding the consequences of antibiotic misuse. In certain countries with insufficient national regulations, this has resulted in the sale of last-resort treatments to the public without requiring a prescription, thus promoting the inappropriate and excessive use of antibiotics.

It now appears that a global initiative is imperative to provide educational and regulatory programs, aimed at enlightening people about the significance of restricting antimicrobial use.

It's crucial to acknowledge that antimicrobial resistance represents an intrinsic and ongoing evolutionary process of adaptation by living organisms.

While it's impossible to entirely prevent microorganisms from undergoing genetic changes and developing resistance to antimicrobial drugs, we can make efforts to decelerate this process and minimize the rapidity of adaptation.

Slowing the spread

One method to impede the process of genetic change on microorganisms involves the responsible administration of antimicrobials, ensuring that they are exclusively administered to animals under the guidance of a veterinary surgeon.

The veterinary surgeon can exercise control over factors like potency, dosage, and treatment duration, thus tailoring the medication to suit the specific target organism and the severity of the infection.

Additionally, the presence of a veterinary surgeon can serve to enlighten the farmer about the heightened risk of AMR if the treatment course is prematurely halted or if an incorrect antimicrobial dosage is employed, potentially leading to the survival of microorganisms and the potential dissemination of resistant bacteria.

The propagation of resistant strains can manifest through several pathways.

For instance, the improper disposal of carcasses infected with pathogens bearing genes responsible for antimicrobial resistance can expose scavenging animals to these pathogens, which can, in turn, transfer AMR strains through their excretions into the surrounding soil or water bodies.

Another contributor to AMR is the release or leakage of antimicrobial manufacturing byproducts or the improper disposal of partially used or expired antimicrobial products, resulting in the contamination of waterways and airborne dispersion through aerosols.

This culminates in the dissemination of resistant strains into the environment, potentially infecting animals and humans who encounter them.

In both cases, a combination of regulation, education, and support can play a crucial role in mitigating or eliminating this mode of transmission.

A global threat

AMR poses a global health threat that transcends national boundaries and cannot be effectively addressed by individual countries in isolation.

Organizations such as WOAH[1] (World Organization for Animal Health), WHO (World Health Organization), NOAH[2] (National Office of Animal Health), and World Animal Protection have actively raised awareness about the issue of AMR and advocated for measures to control and reduce its prevalence.

These agencies collaborate under the WHO's One Health Approach, which aims to integrate human, animal, and environmental ecosystems, recognizing their interdependence.

This holistic approach also considers the environment as a crucial link between humans and animals and a potential source of new resistant microorganisms. Through this multidisciplinary collaboration, they work together to address challenges like AMR and other interconnected issues by developing and implementing programs, policies, legislation, and research to achieve improved public health outcomes.

The European Commission's EU4Health program is committed to enhancing and safeguarding public health within the Union, protecting Union citizens from cross-border health threats, including AMR, and improving the quality of medicinal products, medical devices, and crisis-related items[3].

WOAH promotes the implementation of vaccination programs for both animals and humans, along with a set of management practices that prevent the transmission of infectious agents among animal groups on farms.

These practices also aim to contain infectious agents within farms, which is known as biosecurity.

In 2019, the US Food and Drug Administration (FDA) Center for Veterinary Medicine (CVM) introduced a five-year action plan to support antimicrobial stewardship in veterinary settings.

The 2019-2023 plan seeks to curtail or reverse resistance stemming from antibiotic use in animals while ensuring the continued availability of safe and effective antibiotics for both animal and human use[vii].

The outlook

The One Health Approach seeks to integrate the various aspects of human, animal, and environmental ecosystems that rely on each other.

This approach also takes into account the environment as a crucial link between humans and animals, representing a potential source of new, resistant microorganisms.

This multidisciplinary collaboration is instrumental in addressing challenges like antimicrobial resistance, as well as a myriad of interconnected issues, by formulating and implementing programs, policies, legislation, and research aimed at achieving improved public health outcomes.

According to data from the European Commission, a continued increase in AMR is projected to lead to a staggering toll of 10 million global deaths annually, coupled with a 2 per cent to 3.5 per cent reduction in global gross domestic product. It could potentially cost the world economy up to USD 100 trillion by 2050.

It is abundantly clear that halting AMR is of utmost global significance.

The battle against AMR can gain momentum through the collaboration and active engagement of various government authorities and agencies worldwide, pooling resources and technology to raise awareness.

A multifaceted approach that combines providing appropriate treatment for infections while enhancing preventive and control measures will be instrumental in slowing down the progression of AMR.

Ashwati Sarman is a Graduate Trainee at G&L Healthcare Advisors based in our Belfast office.

References:

[1] WOAH - World Organization of Animal Health- founded as Office International des Epizooties (OIE), which covers Africa, America, Asia and the pacific, Europe and Middle East in the scope of activity

[2] NOAH - National Office of Animal Health (trade association representing the United Kingdom animal health industry)

[3] See ‘Veterinary Medicinal Products – Evolving EU Legislation and Pathways for Change’ for more information on European agencies activities to reduce the threat of AMR

[i]Molecular mechanisms of antibiotic resistance revisited, Elizabeth.M.Darby et al., Nature Reviews Microbiology volume 21, pages280–295 (2023)

[ii]Menz, B. D., Charani, E., Gordon, D. L., Leather, A. J. M., Moonesinghe, R., & Phillips, C. J. (2021). Surgical antibiotic prophylaxis in an Era of Antibiotic Resistance: Common resistant bacteria and wider considerations for practice. Infection and Drug Resistance, Volume 14, 5235–5252. https://doi.org/10.2147/idr.s3...

[iii] International manufacturing and trade in colistin, its implications in colistin resistance and One Health global policies: a microbiological, economic and anthropological study, Muhammad Umair et al., DOI:https://doi.org/10.1016/S2666-...(22)00387-1

[iv] International manufacturing and trade in colistin, its implications in colistin resistance and One Health global policies: a microbiological, economic and anthropological study, Muhammad Umair et al., DOI:https://doi.org/10.1016/S2666-...(22)00387-1

[v] American Veterinary Medicinal Association, Policies available at AVMA definitions of antimicrobial use for treatment, control, and prevention | American Veterinary Medical Association, accessed 18 October 2023.

[vi]World Organisation for Animal Health. (2023, August 16). Antimicrobial resistance - WOAH - World Organisation for Animal Health. WOAH - World Organisation for Animal Health. https://www.woah.org/en/what-we-do/global-initiatives/antimicrobial-resistance/

[vii] Antimicrobial Resistance | FDA

⁷Antimicrobial resistance (who. int)

⁸Veterinary Medicinal Products Regulation | European Medicines Agency (Europa.eu)

⁹Q&A Antimicrobial Resistance (europa.eu)