PUBLIC HEALTH PERSPECTIVE: Antibiotic Crisis

by Sophie Bourquin

For the last 70 years, antibiotics have been used to treat patients with infectious diseases, as a result, associated illnesses and deaths have been reduced considerably. However, antibiotics have been widely used for so long, that the infectious organisms that antibiotics are designed to kill have evolved and adapted to antibiotics, making the drugs less effective.

In some cases, the microorganisms have become so resistant that there are no effective antibiotics available.

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Antibiotic Resistance: several causes

 

Bacteria are living organisms that evolve over time. Their primary function is to reproduce, thrive, and spread quickly and efficiently. Therefore, they adapt to their environments and change in ways that ensure their survival.

Selective pressures, natural selection and also societal behaviors are responsible for antibiotic resistance.

1. Selective pressures and natural selection
Selective pressures (environmental factors which impact reproduction of a population) drive natural selection. In the presence of an antibiotic, bacteria are either killed or, if they carry resistance genes, bacteria survive. Gradually, the population changes, and genes that improve survival and reproduction will become more common while genes that are disadvantageous to survival and reproducti will become more rare. These changes in the genetic makeup of a population happen through mutation or gene transfer, it leads to the evolution of the strain.

Mutation
Most bacteria reproduce by dividing every few hours, allowing them to evolve rapidly and adapt quickly to new environmental conditions. During replication, mutations arise and some of these mutations may help an individual bacterium survive exposure to an antibiotic. (NIH, 2012)

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Gene Transfer
Bacteria also may get genes from each other, including genes that make it drug resistant. (NIH, 2012)

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2. Societal behaviors

As seen previously, the use of antibiotic, even when used appropriately, creates a selective pressure for resistant organisms. However, there are additional societal pressures that accelerate the increased the pace of antibiotics resistance:

Inappropriate Use
Selection of resistant microorganisms is exacerbated by inappropriate use of antibiotics. Sometimes healthcare providers will prescribe antibiotics inappropriately, wishing to placate an insistent patient who has a viral infection or an undiagnosed condition. (NIH, 2012)

Inadequate Diagnostics
More often, healthcare providers must use incomplete or imperfect information to diagnose an infection and thus prescribe an antibiotic just-in-case or prescribe a broad-spectrum antibiotic when a specific one might be better. These situations contribute to selective pressure and accelerate the process of resistance. (NIH, 2012)

Hospital Use
Critically ill patients are more susceptible to infections and, thus, often require the aid of antibiotics. However, the heavier use of drugs in these patients can worsen the problem by selecting for antibiotic-resistant microorganisms. The extensive use and close contact among sick patients creates a fertile environment for the spread of antibiotic-resistant germs. (NIH, 2012)

Agricultural Use
Scientists also believe that the practice of adding antibiotics to agricultural feed promotes drug resistance. For information, more than half of the antibiotics produced in the United States are used for agricultural purposes. (Mellon M, 2001) (National Research Council, Committee on drug use in food animals, 1999)

In his 1945 Nobel Prize speech, Alexander Fleming, who discovered penicillin, warned that bacteria could become resistant to these remarkable drugs. Nevertheless we could wonder what are current evidences showing the burden of antibiotic resistance? What are the health and economic consequences of antibiotic resistance?

Evidence of health and economic burden

In this section, we will first take note of the main strains responsible for diseases as a major public health concern. Hence we will be able to analyze health and economic outcomes related to antibiotic resistance.

1. Strains representing the major public health concern
Here are presented bacteria commonly causing infections in hospitals and in the community (WHO, 2014):

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Here are presented bacteria mainly causing infections in the community (WHO, 2014):

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2. Health outcome associated with antibiotic resistance
The impact of resistance for several of the health outcomes of interest is examined in this paragraph through the following question:

Are clinical outcomes different or worse in patients who are treated for infections caused by bacteria with a specific resistance compared to those who are treated for infections without this resistance?

In order to answer this question we observe significant or insignificant consequences of each resistant strain per specific antibiotic:
– Bacterium-attributable mortality;
– 30-day bacterium-attributable mortality;
– Length Of Stay (LOS);
– Intensive Care Unit (ICU) admission and
– Post-infection Length Of Stay. (WHO, 2014)

The following table summarizes the findings of published scientific literature.
Overview of the findings addressing the health question:

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3. Economic outcome associated with antibiotic resistance
The economic question is addressed through this rationale:

Are economic outcomes and costs different or superior for patients who are treated for infections caused by bacteria with a specific resistance compared to those who are treated for infections without this resistance?

The following table summarizes the findings of published scientific literature:

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All costs for infections caused by resistant strains are consistently greater than those for infections caused by susceptible strains. However the weakness of this economic systematic review is the lack of economic studies (n small). (WHO, 2014)

A study in the USA in which Klebsiella spp and E. coli were included among other Gram-negative bacteria, reported that “patients infected with resistant bacteria had a median total hospital cost US$ 38 121 higher than that for patients infected with susceptible bacteria (US$ 144,414 and 106,293 respectively) (Mauldin PD, 2010)

“Without urgent, coordinated action by many stakeholders, the world is headed for a post-antibiotic era, in which common infections and minor injuries which have been treatable for decades can once again kill” says Dr Keiji Fukuda, WHO’s Assistant Director-General for Health Security.

“Effective antibiotics have been one of the pillars allowing us to live longer, live healthier, and benefit from modern medicine. Unless we take significant actions to improve efforts to prevent infections and also change how we produce, prescribe and use antibiotics, the world will lose more and more of these global public health goods and the implications will be devastating.”

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What actions could be implemented to fight antibiotic resistance?

We can borrow tools that are implemented for the energy crisis. It would be helpful in thinking about how we might want to do this in the case of antibiotics as well.

1. Pay much more attention to conservation
One of the solutions is obvious; we have to better use existing antibiotics. It could be implemented in several ways; these following reflections are ranked from the most tenable to the least achievable.

  • Certainly consumer education works. Very often, people overuse antibiotics or prescribe too much without knowing that they do so. It is necessary to teach patients how not to demand antibiotics and in addition we have to taught doctors how not to use antibiotics as much. In hospitals, a simple example is to put up on a chart the names of surgeons in the ordering of how much antibiotics they used in the previous month. It is a purely informational feedback. Practitioners would be more inclined to rethink how they use antibiotics.
  • Let’s use the energy metaphor: In order to try to rely less on fossil fuels, we have implemented clean energy subsidies. It consists in using non-pollutant fuels instead of fossil fuels. The analogy with antibiotics is that we need to move away from using them and find substitutes. It turns out that anything that reduces the need for antibiotic would really work. It includes improving hospital infection control or vaccinating people.
  • An other option might include tradable permits. In a near future, we might not have antibiotics for many people who have infections; we could then consider the fact to allocate who gets to use some of these antibiotics over others, on the basis of clinical need, but also on the basis of pricing.
  • If we consider energy pricing, for instance, emissions taxes, which means we’re imposing the costs of pollution on people who use that energy. We might consider doing that for antibiotics as well. It would make sure that antibiotics get used appropriately.

2. “Drill baby drill” option
One solution could be to invest more into Research & Development in order to find new antibiotics.

These two first options (better use existing antibiotics and find new ones) can be seen as mutually exclusive: if we invest heavily on new pharmaceuticals, we reduce the incentives for a rational use of drugs. In return if we use our antibiotics appropriately, we don’t necessarily have to make the investments in new drug development.

3. Start looking at other technologies
Researchers have started to look at other technologies. In the same way that energy crisis is an impetus to the development of electric cars; there are some backstop options for the antibiotic crisis. It includes bacteriophages, probiotics, quorum sensing, synbiotics. (Laxminarayan, 2014)

         Conclusion

We face what economists call “tragedy of the commons” with antibiotic resistance (and more broadly with antimicrobial resistance). This problem occurs when multiple individuals, acting solely out of self-interest, ultimately exhaust a limited shared resource despite the fact that it is not in the community’s long-term interests.

Antibiotic (and antimicrobial) use has been called a tragedy of the commons, because although individuals might benefit from the use of antibiotics, concerns exist about the irreparable societal effects of antibiotic resistance developing from the overuse and misuse of antibiotics in clinical and agricultural settings. (Kieran S. O’Brien, 2014)

Interaction of social, demographic and environmental changes that have resulted in the adaptation and genetic mutation of the microbe and other factors like ecological changes, international commerce and travel, technological change, breakdown of public health measures have led to the third epidemiological transition. This transition is marked by the re-emergence of infectious diseases, which have the potential for a global impact. (Bruce J. Fried, 2012)

We have squandered our ability to control; indeed we have not recognized that natural selection and evolution was going to find a way to get back. We need to completely rethink how we’re going to use measures to control biological organisms, and rethink how we use of these valuable resources: antibiotics.

REFERENCES:
WHO. (2014). Antimicrobial resistance : Global report on surveillance. France: WHO Press.

Bruce J. Fried, L. M. (2012). World Health Systems: Challenges and Perspectives.

Kieran S. O’Brien, S. B.-S. (2014). Antibiotic Use as a Tragedy of the Commons: A Cross-Sectional Survey. Computational and Mathematical Methods in Medicine .

Laxminarayan, R. (2014). The coming crisis in antibiotics. Consulté le 2014, sur
TED: http://www.ted.com/talks/ramanan_laxminarayan_the_coming_crisis_in_antibiotics/transcript?language=en#t-686330

National Research Council, Committee on drug use in food animals. (1999). The use of drugs in food animals: benefits and risks. Washington DC: National Academy Press.

NIH. (2012, 03 03). NIAID – Antimicrobial resistance. Consulté le 11 2014, sur NIH: http://www.niaid.nih.gov/topics/antimicrobialresistance/understanding/Pages/default.aspx

Mauldin PD, S. C. (2010). Attributable hospital cost and length of stay associated with health care-associated infections caused by antibiotic-resistant gram-negative bacteria. Antimicrobial Agents and Chemotherapy , 109-115.

Mellon M, B. C. (2001). Hogging it: Estimates of antimicrobial abuse in livestock. Union of concerned scientists .

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One comment

  • Hi Sophie,
    Came across this article when researching on the antibiotic resistance issue, thank you for your insightful thoughts and information, really came in helpful especially when I am working on a school project regarding the antibiotic resistance crisis. This is coming from a 17 year old biomedical science student here in Singapore and am currently working on a report that lack some designs for the cover page of our report. Can we have the permission to use the above photo as the design for our cover pages in the report?

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