Antibioresistance (ABR) is a growing concern that presents a serious threat at a global level. It is happening now and can potentially affect anyone at any age, in any country and at any time. Unfortunately not enough concern is given to it.
Scientific reports and studies lead us to believe that today the world is headed for a “post-antibiotic era”, in which human or animals could die from common and minor infections that are normally treated by antibiotics. The consequences of a “without-efficient-antibiotic world” would be catastrophic, like a throwback to the beginning of the 20th century !
Antibiotics are used to treat many infectious diseases like bloodstream infections (sepsis), diarrhea, pneumonia, urinary tract infections, and also hospital-acquired infections (Saphylococcus aureus), common infections in neonatal and intensive care and to prevent postoperative surgical infections. They affect bacteria by killing them or stopping their proliferation.
Antibioresistance is the ability of a bacterium to resist the action of the antibiotic, resulting in a reduction or elimination of effectiveness of this agent to cure the infection caused by this bacterium. The consequences are dramatic, the treatment is no longer efficient and patients cannot be treated in an effective way anymore, posing a serious risk to public health.
Bacteria can be naturally resistant to an antibiotic (“intrinsic resistance”) or can develop a resistance (“acquired resistance”) when in contact with an antibiotic; in this case it increases the possibility that the bacteria will present new resistances. The acquired resistance warrants substantial perturbation occurring with greater frequency and presenting an exponential growth in difficulty to control. It appears when bacteria, normally susceptible to antibiotics, develop a greater resistance as a result of adaptation through genetic changes to antibiotics. Between 1999 and 2012 the resistance of Escherichia coli to an antibiotic, the fluoroquinolone, increased from 5% to 30% in United States [1]. This emergence of acquired resistance is a natural process belonging to the bacteria in order for it to survive. Its increase is lately becoming a very dangerous problem, in the context of the overuse and the misuse of antibiotics. Due to this, an unintentional acceleration occurs to the normal process through highly increasing the number of new resistances in humans and animals [2-7]. Between 2000 and 2010, total global antibiotic consumption grew by more than 30% based on data from 71 countries [8].
The last WHO report on ABR clearly highlights that “resistance to common bacteria has reached alarming levels in many parts of the world indicating that many of the available treatment options for common infections are becoming ineffective” [9]. Each year in the United Stated, at least 2 million people acquire serious infections with bacteria resistant to one or more antibiotics. At least 23,000 people die each year as a direct result of this antibiotic-resistance. In Europe the number rises to 25,000 people each year [9-10].
This increase in antibioresistance concerns not only humans, but also animals and fishes, mainly in livestock and fish farming. The spread and cross-transmission of those antibacterial resistances; between humans, between animals, between humans and animals, and also the environment, has already been shown and is another element contributing to compounding concern attributing to the situation [9,11].
The significance of this situation is also due to the gaps in surveillance of ABR, and a lack of data sharing and coordination between organizations. The WHO report states that there is a serious lack of global consensus on methodology and data collection for ABR surveillance [9]. Furthermore, no real coordination or harmonized ABR surveillance exists today between the countries or institutions, compromising the ability to assess and supervise the situation. In order to initiate and guide the urgently needed public health actions, a realization of the magnitude of the issue at hand is imperative.
As a result, harmonizing ABR surveillance with common tools and standards is becoming essential to generate reliable basic data in regards to humans, food-producing animals, and more globally in the food chain to take action to contain ABR around the world. As shown in the WHO report [9], the usage volumes of antibiotics in a country correlate with the levels of ABR [12-13]. It has also been shown that when antibiotic use is reduced or stopped the resistance rates usually stabilizes and often falls, especially in the agricultural sector with animals, aquaculture and in the broader environment, where antibiotics are misused and overused. This is, for example, the case in Denmark where the consumption reduction of macrolides in swine food-production correlates with the decrease in the AB resistances among Enterococcus faecium and Enterococcus faecalis [11].
Indeed, antibiotics are habitually given to animals to prevent diseases (and in a very large quantities) due mostly to the awful conditions of animal husbandry, and not in a therapeutic way like it should be.
As a result of food-producing animals farms and aquaculture being reservoirs of pathogens with the potential to transfer resistance to humans, spread of ABR genes and bacteria into the animal sector, and also from animals to human and vice versa, have to be contained. Preventing infections, improving hygiene conditions, sanitation and regulation of water quality are some of the available means of action. Controlling the importation of foods and animals originating from other countries where there is significant doubt over legislation regarding veterinary and phytosanitary policy, as well as food safety in relation to antibiotic use or International Health Regulations, is imperative in order to avoid contamination extension. These actions are essential in order to reduce the inappropriate use of antibiotics in both animals and humans to a minimum.
In order to enhance worldwide ABR detection and promote intersectorial collaboration a global coordination between public health, animal health and food safety is required. This is the “One Health” approach established by a formal tripartite alliance of FAO (Food and Agriculture Organization), OIE (World Organization for Animal Health) and WHO (World Health Organization).
In addition to this, the worldwide ABR public health threat experiences an expansion through the current lack of new antibiotics in the therapeutic arsenal to replace those that have become ineffective. Therefore protecting the efficacy of existing drugs is crucial, as well as developing new ones or new therapeutic strategies to treat infections no longer curable. E.g. 16 new antibiotics were released on the market between 1983 and 1987 but only 2 between 2008-2012 while ABR increased drastically [9]!
Drug research and development is a very long process (around 10 years on average) and is highly costly. Despite the recognized need for new antibiotics, pharmaceutical industries are reluctant to invest money in antibiotics research because their usages correspond to a short-term treatment (a couple of days) compared to the long-term treatment of, for example, diabetes or cardiac diseases resulting in less profits and thereby less return on their investment. They then, in turn, opt to develop drugs that bring a greater return on their investment through selling a greater quantity of a drug and more frequently.
Luckily some European initiatives involving public-private collaborations have taken place lately to speed up the development of therapeutic alternative to tackle the ABR expansion. The “New Drugs for Bad Bugs” is one of these examples. This mission has been launched in 2012 by the “Innovative Medicines Initiative” in order to boost discovery of new drugs.
The situation is so critical in terms of finding new antibiotic molecules that every possibility is being explored in addition to reinstating studies on already known antibiotic classes. Those molecules used to be studied 10, 20, 30+ years ago so in the regard of improved knowledge and accumulated experiences it could be worth it to analyze them again with new tools of research. That would mean, in term of research and development, less time in the evaluation process, and therefore a higher likelihood in finding efficient treatments quickly.
When faced with the need for new antibacterial medications, interest in fundamental research is broadened: development of natural compounds from plants or marine micro-organisms [14-16], and the re-evaluation of some therapeutic alternatives that are forbidden in Europe, but allowed in some other countries like Russia due to being considered too dangerous in the past (like the bacteriophages therapy [17]). There is a possibility that we may be able to apply the tools, which have been developed since these therapeutic alternatives were last visited in order to analyze them with new perspectives and achieve more favorable results.
According to the complexity of developing new therapeutic strategies, prevention appears being the most efficient mode of action to contain the progression of ABR. Doctors, veterinarians, stock breeders, pharmaceutical and food animal production industrials, food consumers, antibiotic consumers, collectively almost all people, so YOU, are concerned! We are all responsible; because of our antibiotics overuse and misuse, we are now already confronting with this dauntingly large problem that would have normally taken years to reach such a level of concern.
So what can we do ?
What can you do ?
WHAT CAN I DO ?
Reduce the use of antibiotic
Antibiotics can only be prescribed by a medical doctor who has examined you, never use them without a prescription, never save them for later use.
They are most of the time inappropriate: 80% of the common winter illness affecting your nose, ears, throat and lungs (like sore through, cold, flu) have a viral and not bacterial origin meaning that antibiotics are not needed to treat your disease and more importantly they are ineffective [18-21]!
When they are misused, they will not help you to get better faster and may cause side effects (diarrhea, nausea or skin rashes) [22].
In case of bacterial infection, compliance with your treatment is essential
This means that the duration of the treatment has to be respected even if you feel healthy before its end.
Why? It enhances the selection of the most resistant bacteria, the most sensitive would have already been killed by the antibiotic in the first days of the treatment.
Control the origin of food, promote the consumption of organic products
The usage of antibiotic is strictly under controlled conditions, at least more than the conventional agriculture where antibiotics are often misused!
Prevent the spread of infections…without becoming subject to paranoia either
Classical every day life precautions like the regular washing of hands, avoiding contact with sick people etc. are often sufficient to protect yourself and others against common illnesses.
BIBLIOGRAPHY:
[1] The center of disease dynamics, economics and policy.
[2] Bell BG, Schellevis F, Stobberingh E, Goossens H, Pringle M. A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance. BMC Infect Dis 2014;14:13.
[3] Chung A, Perera R, Brueggemann AB, Elamin AE, Harnden A, Mayon-White R, et al. Effect of antibiotic prescribing on antibiotic resistance in individual children in primary care: prospective cohort study. BMJ 335(7617):429.
[4] Donnan PT, Wei L, Steinke DT, et al. Presence of bacteriuria caused by trimethoprim resistant bacteria in patients prescribed antibiotics: multilevel model with practice and individual patient data. BMJ 2004;328(7451):1297-301.
[5] London N, Nijsten R, Mertens P, van den Bogaard A, Stobberingh E. Effect of antibiotic therapy on the antibiotic resistance of faecal Escherichia coli in patients attending general practitioners. J Antimicrob Chemother 1994;34(2):239-46.
[6] Malhotra-Kumar S, Lammens C, Coenen S, Van Herck K, Goossens H. Effect of azithromycin and clarithromycin therapy on pharyngeal carriage of macrolide-resistant streptococci in healthy volunteers: a randomised, double-blind, placebo-controlled study. Lancet 2007;369(9560):482-90.
[7] Nasrin D, Collignon PJ, Roberts L, Wilson EJ, Pilotto LS, Douglas RM. Effect of β lactam antibiotic use in children on pneumococcal resistance to penicillin: prospective cohort study. BMJ 2002; 324(7328):28-30.
[8] Van Boeckel TP, Gandra S, Ashok A, Caudron Q, Grenfell BT, Levin SA, Laxminarayan R, Global antibiotic consumption 2000 to 2010: an analysis of national pharmaceutical sales data. Lancet Infect Dis. 2014; 14(8):742-50.
[9] Antimicrobial resistance: global report on surveillance. WHO. 2014.
[10] U.S. Department of Health an Human Services. Centers for Disease Contol and Prevention.
[11] Wegener HC. A15 Antibiotic resistance-Linking human and animal heakth. National Academies Press (US). 2012.
[12] Collignon P, Athukorala PC, Senanayake S, Khan F. Antimicrobial Resistance: The Major Contribution of Poor Governance and Corruption to This Growing Problem. PLoS One. 2015; 10(3): e0116746.
[13] Landers TF, Cohen B, Wittum TE, Larson EL. A Review of Antibiotic Use in Food Animals: Perspective, Policy, and Potential. Public Health Rep. 2012; 127(1): 4–22.
[14] Hayashi MA, Bizerra FC, Da Silva PI. Antimicrobial compounds from natural sources. Front Microbiol. 2013; 4: 195.
[15] Wong SY, Grant IR, Friedman M, Elliott CT, Situ C. Antibacterial activities of naturally occurring compounds against Mycobacterium avium subsp. Paratuberculosis. Appl Environ Microbiol. 2008 Oct;74(19):5986-90.
[16] Jang KH, Nam SJ, Locke JB, Kauffman CA, Beatty DS, Paul LA, Fenical W. Anthracimycin, a potent anthrax antibiotic from a marine-derived actinomycete. Angew Chem Int Ed Engl. 2013 Jul 22;52(30):7822-4.
[17] Sulakvelidze A, Alavidze Z, Morris JG Jr. Bacteriophage therapy. Antimicrob Agents Chemother. 2001 Mar;45(3):649-59.
[18] Arroll B, Kenealy T. Antibiotics for the common cold and acute purulent rhinitis. Cochrane Database Systematic Reviews 2013 Jun 4;6:CD000247.
[19] Arroll B, Kenealy T, Falloon K. Are antibiotics indicated as an initial treatment for patients with acute upper respiratory tract infections? A review. NZ Med J 2008;121(1284):64-70.
[20] Smith SM, Fahey T, Smucny J, Becker LA. Antibiotics for acute bronchitis. Cochrane Database of Systematic Reviews 2014, Issue 3. Art. No.: CD000245.
[21] Mäkelä MJ, Puhakka T, Ruuskanen O, et al. Viruses and bacteria in the etiology of the common cold. J Clin Microbiol 1998;36(2):539-42.
[22] Shehab N, Patel PR, Srinivasan A, Budnitz DS. Emergency department visits for antibiotic-associated adverse events. Clin Infect Dis 2008;47(6):735-43.
UPDATE
Antimicrobial resistance still high, EU report
Chloé Clouzeau is a Doctor of Pharmacy and Toxicology living in Berlin. After a PhD in Research and Development in Ophtalmology, she graduated from Université Paris Descartes and Paris Sud XI.