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Antibiotic Resistance: The Presidential Order

Updated on April 11, 2015

Penicillin, the first natural antibiotic discovered by Alexander Fleming in 1928

Penicillin core" by Yikrazuul - Own work. Licensed under Public Domain via Wikimedia Commons
Penicillin core" by Yikrazuul - Own work. Licensed under Public Domain via Wikimedia Commons | Source

INTRODUCTION. From the era of wonder drugs to the post antibiotic age?

An executive order was issued on September 15, 2014 describing a National Strategy, and a longer term National Action Plan was announced on March 27 2015, both giving directives to combat antibiotic resistance.

Most of us know how much the discovery of antibiotics and their introduction into medical practice contributed to our health, well- being, and longevity during the last century. At the beginning of the twentieth century, the leading cause of death was due to some type of infection by bacteria; within a hundred years, death due to bacterial infection had greatly declined, and some diseases caused by bacteria, such as tuberculosis, had almost disappeared. Antibiotics became routinely used to turn once feared diseases –many of which attacked children – into easily treatable conditions. We became used to the assumption that no matter what infection our loved ones or we caught, a few days of antibiotic treatment would get rid of the pathogen, and we would then go on to get better. It is also clear that without the aid of antibiotics to prevent and mitigate infection, the risks in medical intervention by every type of surgery, immunotherapy and chemotherapy would be unacceptably high.

By today, few of us have not heard about the threat of resistant strains that are unresponsive to antibiotics. The use of many well-known antibiotics is limited because of resistance, and this includes some of the ‘last resort ‘ antibiotics. Perhaps you heard about cases in the media: people who died because no effective antibiotic could be found, or you yourself experienced delay in treatment because an antibiotic prescribed did not work and you had to be started on a new one. But instead of anecdotal stories let us look at the statistics at the White House’s site: ‘According to the Centers for Disease Control and Prevention (CDC), antibiotic-resistant infections are associated with 23,000 deaths and 2 million illnesses in the United States each year. Estimates of annual impact … have ranged as high as $20 billion ...’.

On the Nature of Antibiotic Resistance

Why and how does antibiotic resistance develop in microbes? Against what types of drugs is resistance developing?

No in depth set of answers can be given in the space immediately available here, the explanations will have to be given in subsequent articles. But, in short: antibiotic resistance is a natural phenomenon, with probably all microbes having the ability to develop resistance against some, and possibly all drugs. Nevertheless, depending on their mode of operation, the action of some drugs may be more difficult for microorganisms to neutralize.

Infographic from the CDC Threat Report 2013, Antibiotic resistance threats in the United States

CDCinfographicANTIBIORESISTANCE" by Centers for Disease Control and Prevention - Antibiotic resistance threats in the United States, 2013. Licensed under Public Domain via Wikimedia Commons
CDCinfographicANTIBIORESISTANCE" by Centers for Disease Control and Prevention - Antibiotic resistance threats in the United States, 2013. Licensed under Public Domain via Wikimedia Commons | Source

Why is the spread of resistance so pervasive? Why aren’t new drugs developed?

Firstly, it needs to be said that when we use a particular antibiotic, the appearance of resistance to it involves the selection of those bacteria capable of circumventing its action because of a biochemical change in the cell caused by a mutation. The bacteria that are susceptible to it are killed, whilst those that have some way of evading its action, in other words are ‘resistant’ to it, survive and go on to replace the sensitive ones that are killed by the antibiotic. This happens in many ecological niches - unfortunately such as hospitals or medical equipment, or in the general community. The more frequently bacterial populations encounter the antibiotic, the more likely it is that eventually one of them will include some bacteria that are resistant. Thus, although antibiotic resistance can appear without any help from us, the situation is greatly aggravated by human activity of overusing antibiotics, and enhanced by the global spreading of resistant strains.

The development of new antibiotics slowed and almost came to a complete stop during the past 40-50 years, because it was not easy to find novel structures with antibiotic activity. Also, as resistance became more prevalent, development of new antibiotics became less attractive to drug companies because they became aware that there would be a limit to their useful lifetime.

A colleages showing some of the bacteria species

BacteriaColleage" by PeskyPlummer - Own work. Licensed under CC BY-SA 3.0 via Wikimedia Commons
BacteriaColleage" by PeskyPlummer - Own work. Licensed under CC BY-SA 3.0 via Wikimedia Commons | Source

Which microbes are resistant?

As stated above, probably many or all microorganisms have had the opportunity to encounter, and develop resistance against some form of noxious natural substance (i.e. antimicrobial or antibiotic). The Centers of Disease Control and Prevention (CDC) has identified 18 types of the most hazardous drug-resistant microorganisms and divided them into 3 classes: urgent threats, serious threats, and concerning threats. All of these 18 types of bacteria can pose severe health risks, with several of them being involved in fatal infections. Almost all organisms shown to cause sepsis (http://hubpages.com/hub/How-To-Understand-Blood-Poisoning-Septicaemia) are found in the 18 major drug-resistant threats.

The Components of the President’s Executive Order

The Executive Order involves both governmental agencies and non- governmental experts in making plans to combat antibiotic resistance.

It establishes a new task force from the departments of Defense, Agriculture, and Health and Human Services to submit a National Action Plan

It also charges this task force with creating a Presidential Advisory Council from non-governmental experts to give advice and make recommendations for the actions to be taken

US-WhiteHouse-Logo" by U.S. federal government - Extracted from PDF version of a 2003 progress report (direct PDF URL http://www.whitehouse.gov/).. Licensed under Public Domain via Wikimedia Commons
US-WhiteHouse-Logo" by U.S. federal government - Extracted from PDF version of a 2003 progress report (direct PDF URL http://www.whitehouse.gov/).. Licensed under Public Domain via Wikimedia Commons | Source

The Executive Order contains the following directives to achieve, with the help of the above agencies

♦ To improve Antibiotic Stewardship to preserve antibiotic effectiveness through:

New rules and regulations for antibiotic use in hospitals and other in-patient facilities, as well as in outpatient and long term settings

Decreasing and eliminating agricultural use of medically important antibiotics, and developing alternatives to the use of antibiotics

♦ To promote the discovery of new antibiotics and diagnostics:

By facilitating steps needed for drug companies to develop new antibiotics

By improving the infrastructure of clinical trials

♦ To strengthen International Cooperation – a prerequisite for success in a world of global connections

♦To provide details for required actions in a National Strategy, which in addition to the above goals includes:

Improved identification and reporting of antibiotic resistance

Rapid diagnostic tests for the identification of resistant bacteria

And

♦ To launch a $20 million prize for the first development of a rapid diagnostic tests

Antibiotic resistance tests

Bacteria in the culture on the left are susceptible to the antibiotic in each disk, as shown by the dark, clear rings where bacteria have not grown.  Dr Graham Beards - Own work. Licensed under CC BY-SA 3.0 via Wikimedia Commons
Bacteria in the culture on the left are susceptible to the antibiotic in each disk, as shown by the dark, clear rings where bacteria have not grown. Dr Graham Beards - Own work. Licensed under CC BY-SA 3.0 via Wikimedia Commons | Source

A $20 million prize for a rapid diagnostic test! Is it this that important?

The figure shows the classical way of determining antibiotic resistance in a sample. For this, bacteria need to be grown under laboratory conditions – a time consuming process. By now, there are some faster molecular methods available, but there is further need to develop sufficiently fast, easily usable point of care (bedside) tests.

As Drs. Anthony S. Fauci and Francis S. Collins from the NIH pointed out in their post responding to the Executive order, fast detection of the infecting pathogens would allow for the antibiotic to be tailored for treating the infection. This will minimize the use of broad-spectrum antibiotics (those that act against a wide range of disease-causing microbes), prescribed to ease symptoms while doctors wait for 2-3 days to grow the pathogen for identification.

Clearly, all of the actions and precautions listed the Executive Order need to be taken to form a global network of actions and policies, so we can safely rely on efficient treatment of infectious disease.

Rererences

Some of the resources used:

https://www.whitehouse.gov/the-press-office/2014/09/18/fact-sheet-obama-administration-takes-actions-combat-antibiotic-resistan;

https://www.whitehouse.gov/blog/2015/03/27/our-plan-combat-and-prevent-antibiotic-resistant-bacteria

http://www.cdc.gov/drugresistance/biggest_threats.html

http://www.davolterra.com/content/antibiotics-wonder-drugs

http://www.who.int/mediacentre/factsheets/fs194/en/

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    • Eva Hard profile imageAUTHOR

      PE Hardwicke 

      3 years ago from Midwest USA

      Thanks a lot Bill. I myself learn quite a bit through writing them, but it takes a long time to write. I marvel how you can post so many good stories and pieces of advice.

    • billybuc profile image

      Bill Holland 

      3 years ago from Olympia, WA

      I'm learning much from your articles so I thank you. This is so much more interesting than reading another recipe for meatloaf. :)

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