The bugs are fighting back against the drugs (and they are winning)

WHO changed its annual World Antibiotic Awareness Week, which focused on drugs that treat bacterial infections, to World Antimicrobial Awareness Week last year, to widen the scope to include drugs that treat all infectious diseases, whether bacterial, viral, fungal or parasitical. — AFP

Like non-communicable diseases (NCDs), many describe antimicrobial resistance (AMR) as a silent epidemic.

However, World Health Organization (WHO) Department of Global Coordination and Partnership on AMR director Dr Haileysus Getahun feels that it is more like an active volcano that is constantly erupting.

Although there are no comprehensive statistics on the overall impact of AMR in the world, there is sufficient data to already paint a worrying picture.

Among the dangerous microorganisms that are displaying an increasing resistance to current drug treatment are those that cause common infections like:

• Urinary tract infections
• Sepsis (a life-threatening condition where the body overreacts to an infection)
• Sexually-transmitted diseases (STDs) – in particular, gonorrhoea and AIDS (acquired immunodeficiency syndrome)
• Pneumonia
• Tuberculosis
• Malaria, and
• Candidiasis.

A significant number of these microorganisms are resistant to two or more drugs that are presently being used to kill them.

Adding on to that is the fact that there is a significant dearth in the pharmaceutical pipeline for new antibiotics.

“The private pharma(ceutical) industry has, one after the other, been exiting from the research and development of the antibiotics pipeline in the last decade in particular,” notes Dr Getahun.

The director of the Tripartite Joint Secretariat on AMR – comprising the Food and Agriculture Organization (FAO), World Organization for Animal Health (OIE), WHO, and more recently, the United Nations Environment Programme (Unep) – adds that this is due to the fact that antibiotics are not profitable for these companies.

The situation is so concerning that the WHO declared AMR to be among the top 10 global health threats in 2019.

It’s not you, it’s your bugs

During the virtual media briefing where Dr Getahun spoke, a Zimbabwean journalist shared that they had discovered they were resistant to amoxicillin, penicillin and co-trimoxazole – all commonly-used antibiotics – during testing prior to starting anti-retroviral therapy, even though they had never previously misused antibiotics.

This anecdote serves to illustrate two important factors in AMR.

One, that it is not actually the person who is resistant to drugs, but the microorganisms inside them.

There exists an entire community of microorganisms that live on and inside us humans.

Known as the human microbiome, it consists of bacteria, fungi and viruses, among others, that can be helpful, or at least harmless, to their human host under normal circumstances.

Like a gun that does not discriminate against the innocent or guilty, when we humans take antimicrobials, both the harmful and helpful (or neutral) microorganisms are wiped out.

If we do not complete the entire course of antibiotics as prescribed, or were not given the correct dosage and/or prescription, some of these microorganisms might survive and mutate to develop resistance against the drug we took.

As Dr Getahun notes: “AMR is a natural phenomenon, as microbes, be they bacteria, viruses, fungi or parasites, always try to thrive and change over time, so that they will stop responding to treatment.

“And this in turn can cause spread of infections, diseases, as well as deaths.

“And we know, ever since Alexander Fleming discovered penicillin – the first antibiotic – resistance development has been an inherent part of the action of these drugs.”

However, he adds that there are drivers that can accelerate the spread of AMR, like the misuse and abuse of antimicrobials.

As we have learned from the Covid-19 pandemic, it is very easy to “share” our bugs – all it takes is a couple of touches to the right places from one person to another (sometimes via other surfaces), or maybe even just a casual, close conversation where minute droplets bearing microorganisms can land on one another.

In such a manner, drug-resistant microorganisms can easily hop from person to person, conferring upon them their Trojan horse gift of AMR, even if – like the Zimbabwean journalist – they themselves have never misused antimicrobials.

Despite the fact that Covid-19 is a viral disease, antibiotics were given to as many as 80-90% of such patients, according to Dr Getahun. — US CDC/dpa

It’s humans, animals and plants

The second factor is that the root causes of AMR are far more pervasive than just antimicrobial misuse by people.

Says Dr Elizabeth Tayler, who is the WHO technical lead for the Tripartite Joint Secretariat on AMR: “Humans have been misusing antibiotics, but we’ve been abusing them not only in the human health sector, but also in fish farming, in animal farming – increasing livestock and treating animals that are sick.

“We have inadequate water sanitation, dischargement of antimicrobials into water, and increasingly, [antimicrobials] in what is being sprayed on crops.

“The more we use antimicrobials in any sector, the greater the chances that resistance will develop and that these drugs will become ineffective.”

In addition to patients not completing their antimicrobial course or not taking them properly, Dr Tayler notes that these medications are often used as substitutes for decent infrastructure, hygiene measures, and proper diagnosis and treatment.

“Over 30% of health facilities don’t have running water or a clean toilet, so it’s very difficult to practise good hygiene in those environments and antibiotics are used as a cheaper substitute,” she says.

“This is an issue in the developing world, but it is also as much an issue in developed countries, where there is still very widespread use of antibiotics in the prevention of infection and treating infections that don’t respond – things like flu where antibiotics don’t work, but are still being used.”

Flu, short for influenza, is a viral infection that does not respond to antibiotics, which are meant for bacteria.

Dr Tayler notes that in some countries, antimicrobials are available over the counter, where neither the seller nor the buyer are aware of how the medication should be used and the quality of the drug is suspect as well.

“This is a problem in the human sector, but it is as much a problem in the animal sector, where there is a big push to intensify livestock production – very often in unsanitary facilities with poor biosecurity, so a lot of antibiotics are used to prevent infections.

“Or if there is a small risk of infection in a herd, the whole herd will be treated,” she says.

“Antibiotics in many countries are also being used to promote growth in animals, so in many countries, more antibiotics are being fed to healthy animals than to sick humans and sick animals,” she adds.

Another increasingly prominent problem is the use of antimicrobials in the agriculture sector.

Dr Tayler points out that the antibiotics streptomycin and tetracycline are being sprayed on orange trees in California, United States, as well as rice crops.

Meanwhile, antifungals are being used on flowers, which has already been linked to drug-resistant aspergillus in humans.

“One of the problems is that this then leaches into the environment, into the rivers.

“We have antibiotic residue as a waste product of food production, washing off fields, washing off from animal production and from hospitals, and all ending up in the water supply where people are bathing, where they are getting their drinking water.

“Very often there are high levels of bacteria in these waters as well if there’s inadequate sanitation.

“So that’s a pretty toxic soup in which resistance in bacteria will develop, thrive and be transmitted,” she explains.

AMR action plans

The WHO has had a Global Action Plan on AMR formulated since 2015.

That year saw countries worldwide commit to the framework laid out in the Plan, as well as to develop and implement their own national action plans to tackle AMR, during the World Health Assembly (including Malaysia).

WHO AMR Division National Action Plan and Monitoring Unit technical officer (AMR) Dr Sarah Paulin notes that as there are so many drivers in AMR – as mentioned above – the action at country level has to be multisectoral.

“It has to be coordinated across sectors and within the various departments.”

There are five strategic objectives contained in the Global Action Plan that are meant to serve as a blueprint for each country’s own plan. They are:

• To improve awareness and understanding of AMR through effective communication, education and training.
• To strengthen the knowledge and evidence base through surveillance and research.
• To reduce the incidence of infection through effective sanitation, hygiene and infection prevention measures.
• To optimise the use of antimicrobial medicines in human and animal health.
• To develop the economic case for sustainable investment that takes account of the needs of all countries and to increase investment in new medicines, diagnostic tools, vaccines and other interventions.

Notes Dr Paulin: “The five strategic objectives are comprehensive in nature, given that the actions at country level are complex and cut across different thematic areas, and also different sectors.”

However, one barrier to the implementation of such action plans is sustainable funding.

“When we look at national action plans, political leadership is one important aspect.

“The second important aspect is actually being able to implement it because you have the resources and the financing to do so.

“But up until now, only 20% of our national action plans are fully costed and funded.

“And so there’s a major gap that we still need to fill in terms of being able to accelerate comprehensive implementation,” she says.

Tan Shiow Chin is a 2021 APCAT Media Fellow.