The emergence of antibiotic resistance: how can we put a stop to it?

We are entering a new phase of the antibiotic era in which the prevalence of antibiotic resistance dictates how we treat invasive microbial pathogens. We can no longer predictably rely on the availability of safe, cheap, highly effective antibiotics to manage infectious diseases. Here to tell us more for European Antibiotic Awareness Day is Steven Opal.

Two important documents have appeared this year which highlight the depth of the problem that we find ourselves in with regard to antibiotic resistance throughout the world.

The first is a country-specific, worldwide, situational analysis of the challenge of antibiotic resistance produced by the World Health Organization in April, 2015.

The second is a document created by The Center for Disease Dynamics Economics and Policy which is a think tank from Washington, DC and New Delhi, India that is entitled “The State of the World’s Antibiotics-2015.”

Both documents provide a sobering reminder of how dire the situation has become in many areas of the world and how progressive antimicrobial resistance now threatens the sustainability of antimicrobial chemotherapy as a standard treatment option for many common infectious diseases.

How could the wonder drugs of the 20th century rapidly become ‘endangered species’ by the early 21st century?

A few statistics to consider

Of the tens of thousands of tons of antibiotics produced each year, at least two-thirds of these precious drugs are used for non-medical use (to support animal husbandry or as pesticides for agriculture).

At least 50% of their use in agriculture is given in subtherapeutic levels presumably as growth stimulants, for which there is little evidence this use of antibiotics actually works. Antibiotics pollute the fields of farms and ranches serving as a breeding ground of the generation and spread of resistance genes among soil bacteria that later end up in the food chain.

The widespread release of water-born antibiotics to prevent infections and support the burgeoning aquaculture industry has enormous adverse environmental consequences favoring the dissemination of antibacterial resistance genes.

Up to 80% of all antibiotics for human use are used for outpatient infections. Most disturbingly, estimates indicate that at least one-third of antibiotic prescriptions generated annually by physicians are considered inappropriate and will not improve the clinical situation of the patient.

What can be done at the present time to stem the tide of antibiotic resistance?

Numerous elements of the antibiotic resistance problem are within the control of physicians in the way we prescribe antibiotics. There are at least ten things that we can do as clinicians to improve the situation:

1) The first priority is to recognize that it’s a threat to the health of all citizens. It is heartening to see countries coming to this realization such as the antibiotic resistance program run by David Cameron in the UK and the President’s executive order for research to reduce the incidence of antibiotic resistance in the US. Similar societal initiatives need to be undertaken to solve the problem of antibiotic resistance.

Clinicians can improve the situation by being an advocate for discontinuation of nonmedical use of antibiotics and antibiotic use in agriculture.

2) Clinicians can improve the situation by being an advocate for discontinuation of nonmedical use of antibiotics and antibiotic use in agriculture. This has to stop and has to be regulated in an intelligent fashion. Clearly antibiotics can assist in veterinary medicine in treating infections in animals, but their use as growth promoters and pesticides is destructive to the environment and should be banned.

3) There should be strict control over antibiotic manufacturing and prescribing. There should be no over-the-counter (OTC) antibiotics available. This is in the purview of licensed physicians who are responsible for their safe and correct use. India has taken bold steps recently to ban OTC antibiotics and other countries should do the same.

4) We need to educate physicians and their patients, veterinarians and lawmakers about the threat of antibiotic resistance and need to curtain the unnecessary use of antibiotics. These drugs are a precious commodity for humankind and should not be wasted.

5) We need to continue to promote the development of new classes of antimicrobial agents to replace older agents which are no longer effective because of progressive antibiotic resistance. This has become a real challenge as relatively small numbers of new drugs have recently entered the market to deal with antibiotic-resistant pathogens. This situation has been improving in the last year or two where a substantial number of new antibiotics have been added to our therapeutic armamentarium.

We need to promote the use of non-antibiotic therapies to prevent or treat infectious diseases.

6) We need to promote the use of non-antibiotic therapies to prevent or treat infectious diseases. Vaccines against common bacterial pathogens such as Streptococcus pneumoniae, Haemophilus influenzae, and meningococcal disease have been highly effective and reduced the need for treating these infections with antibacterial agents. Other immune based therapies, or probiotics, alterations of the microbiome, bacteriophages and another number of other ideas of non-antibiotic treatments for infectious diseases need to be supported.

7) We need to encourage the healthy and wealthy nations to invest time and effort in the prevention treatment of infectious diseases worldwide. This idea of ‘enlightened self-interest’ is particularly true in the treatment of contagious infectious diseases such as tuberculosis, influenza and other readily transmittable pathogens which can effect low and middle income countries but also spread rapidly to be global health issues. We should not ignore the plight of our colleagues in low income countries who are dealing with multiple drug resistant (MDR) pathogens on a daily basis.

8) We must improve our diagnostic capabilities to rapidly determine who has a treatable infection that would respond to an antimicrobial agent.

At least 15% of the world’s supply of antimicrobial agents has been found in various surveys to be substandard.

9) The use of substandard antibiotics is a major problem. At least 15% of the world’s supply of antimicrobial agents has been found in various surveys to be substandard (either adulterated in their formulation, having reduced concentrations of antibiotics than listed on the label, and post- dated antibiotics which have lost activity because of inadequate storage and no longer have potency). This is a particular problem in low income countries where they can ill afford to be burdened with substandard antibiotics.

10) Protect the antibiotics we have and prevent the spread of MDR-pathogens in health care settings. We all need to advocate for appropriate antibiotic use and become stewards for these magnificent drugs. Lastly, get involved. Join WAAAR (world alliance against antimicrobial resistance). This is an academic advocacy group started by Jean Carlet in Paris a few years ago that champions the cause of saving antibiotics for future generations.

A recent series of papers have been listed in Critical Care have highlighted the problem of antibiotic resistance and offered some potential solutions. These papers have detailed the value of antibiotic stewardship, the prevention of the spread of MDR pathogens in the intensive care unit setting, providing guidance for treating extreme drug resistant pathogens.

The value of selective decontamination of the digestive tract as a way of preventing the spread of antibiotic resistance genes rather than promoting antibiotic resistance is also discussed. This controversial topic is covered in a recent review in Critical Care.

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