Together with their European and global counterparts, executives of the Spanish Agency of Medicines and Sanitary Products (AEMPS) have stated that human and animal health require the same battle against Antimicrobial Resistance (AMR). This argument was emphasized in the course of an international symposium that was convoked to analyze the relation between consumption of antibiotics and the transmission of antimicrobial resistance from animals to humans. The first Spanish Joint Interagency Antimicrobial Consumption and Resistance Analysis Report (JIACRA) on the subject of antibiotic consumption and antibiotic resistance was presented during the symposium.
Emilio Bouza, PhD, an executive of the scientific board of the Ramón Areces Foundation with hosted the event, expressed his satisfaction and gratitude for having been called to introduce a conference centered on his own research specialty. He highlighted the Foundation’s specific goal of promoting the dissemination of key aspects related with the biosciences.
Belén Crespo, director of the AEMPS (Spanish Agency of Medicines and Sanitary Products), reminded her audience that the UN has singled out AMR as a public health problem of the first order worldwide. This has given rise to a global program undersigned by 193 countries (including Spain). The am is to advance toward a joint commitment to fight antibiotic resistance.
Belén Crespo highlighted that the mortality rate associated with multiresistant bacteria has diminished in Spain: after 3,058 deaths in 2015, the new figure amounted to only 2,956 registered deaths associated with the same cause in 2016.
Regarding the JIACRA report published for the first time in 2015, the speaker reaffirmed that she was able to count on the support of EFSA (the European Food Safety Agency), ECDC (the European Centre for Disease Prevention and Control), and EMA (the European Medicines Agency).
For that reason, Ms Crespo drew her audience’s attention to the 2nd edition updated in 2017 entitled “One Health”. The report’s main conclusion is that all types of microbial resistance to antibiotics in humans as well as in animals have a common origin in the widespread utilization of those very medicines.
Although she expressed sincere satisfaction with the good progress exhibited by the Spanish National Plan to Counteract Antibiotic Resistance (PRAN), Ms Crespo highlighted the difficulties in coordinating the plan on a territorial level – an aspect that has led her to call on the Agency she represents, as well as on all other administrations, to attain more reasonable usage figures that reflect a more prudent application of antibiotics. As Crespo points out, such efforts should already begin in the medical treatment of infants.
Pilar Ramón-Pardo, the regional assessor in matters of Antimicrobial Resistance (AMR) for the Pan American Health Organization (PAHO), focused her contribution on AMR, portraying it as a threat that requires immediate action while at the same time opening up a series of opportunities and challenges in terms of public health policies.
To introduce her lecture, the speaker explained that mortality caused by infectious diseases has been descending worldwide since the mid-20th century, although the rate remains elevated in poor countries due to the seriousness of diarrheic and respiratory diseases in children under 5.
Ms Pilar Ramón-Pardo directly associated that problem with those nations’ low level of socio-economic development, as addressed by the Third UN Global Objective.
As an example, she explained that the World Bank has quantified the impact of AMR on the GNP of countries with medium-low and low incomes: it exerts a negative effect on food production as well as on livestock breeding, and it provokes a series of trade restrictions.
This led to a Global Action Plan adopted by the FAO (Food and Agriculture Organisation of the United Nations), the OIE (World Organisation for Animal Health) and the WHO, and which led to a worldwide resolution adopted on 21 September 2016, thereby creating a specific coordinating group and implicating the governments of participating countries to apply firm political commitment.
Ramón-Pardo enumerated five basic axes of the Global Action Plan on Antimicrobial Resistance: 1) improving general awareness, 2) developing surveillance and monitoring, 3) reducing the incidence of infections associated with public health institutions, 4) increasing the global offer in terms of innovative antibiotics, and 5) increasing public investment in all countries in their efforts to contain AMR.
To illustrate Axis 1), the speaker referred to the World Antibiotic Awareness Week which will be celebrated from 12 to 18 November 2018 and which is inspired by a European example.
To illustrate Axis 2) Ramón-Pardo mentioned the example of the spread of Klebsiella pneumoniae in South America, which led the World Health Organization in January 2018 to launch the Global Antimicrobial Resistance Surveillance System (GLASS), which integrally monitors clinical and laboratory data.
Within the framework of Axis 3), Ms Ramón-Pardo related the fact that hand hygiene, vaccination, and the optimized use of antimicrobials are all being promoted in health institutions: for instance, a model study is being implemented in Andalusia. She associated these developments with the prioritization of antimicrobial agents, but also presented the discouraging fact that only seven innovative antibiotic substances are expected to be introduced in the years to come.
In her function as a representative of the World Health Organization, Ms Ramón-Pardo highlighted the inequalities that reign among different regions of the world, and the discrepancies in terms of the speed with which national action plans are implemented. In that respect she pointed out that in certain countries where the primary sector is more efficient than the health sector; in any case, AMR needs to be addressed with a multisectorial strategy. Furthermore, as she pointed out, animal health often lags behind the progress achieved in human health.
The speaker concluded her talk with a discouraging figure: in the year 2050 it is estimated that one death will occur every three minutes due to AMR, thereby attaining an incidence higher than cancer. She therefore called on all participating nations to devote more resources, improve governance, monitor the problem more closely, and propose new products to address it.
All of these observations are associated with a currently open discussion regarding a possible leadership role to be assumed by developed countries in favor of action plans carried out in the poorer nations; the private sector could likewise be enrolled in each country’s national action plan. She cited the collaborative examples of Canada, Japan and Korea, contrasting them with mistakes previously made in countries such as Sweden and Holland, and which now can be avoided in other countries.
Jordi Torren, the coordinator of the European Medicines Agency’s project “European Surveillance of Veterinary Antimicrobial Consumption” (ESVAC), offered an analysis of the most recent European data regarding consumption and sales of antibiotics for use in animals. After having estimated that 25,000 people die in Europe each year from infections stemming from multiresistant bacteria, he added that it is expected that Antimicrobial Resistance (AMR) will surpass cancer in 2050 as the principal cause of death in humans, with an annual mortality rate of 10,000,000.
Jordi Torren specified that four European agencies are currently devoting their energies to the problem: the above-mentioned EMA (European Medicines Agency), the ECDC (the European Centre for Disease Prevention and Control), EFSA (the European Food Safety Authority), and EEA (the European Environment Agency). These organizations collaborate with their counterparts in the U.S. and in Korea.
The European coordinator drew his audience’s attention to the danger incurred by all of humanity in case antibiotics become inefficient. Phages and vaccines could be considered as alternative strategies, and a change in the business model of pharmaceutical companies could to make it more attractive for them to invest in new developments.
Apart from encouraging participating organizations to promote the availability of new diagnostic tests, Mr Torren highlighted the need to increase hygienic standards in farm holdings and livestock farms. A first success has been obtained in a decrease observed in the use of growth promoters in animals – a decrease, however, which is more notable in Europe than in the U.S., as he pointed out.
All previous observations did not prevent the speaker from reminding his audience that antimicrobial agents are also essential in the treatment of infectious pathologies in house pets or in meat destined for human consumption.
As Torren noted in his quality of representative of the European Medicines Agency, no direct relation can be observed between countries that have large farm holdings and an increased consumption of antimicrobials for purposes of production: Denmark and the Netherlands, for instance, are countries well known for their immense swine and avian holdings.
Mr Torren also explained that the European Union applies a total of 11 indicators for the use of antimicrobials according to meat mass, country and type of antibiotic: cephalosporins, polymyxines, quinolones, and fluoroquinolones. Within this general framework, the scores obtained by Spain cannot be considered satisfactory.
Furthermore, this speaker explained that, ever since the discovery of Mcr-1 gene, the maximum recommended dose of colistin has been brought down to 5 mg for every kg of produced animal meat regardless of livestock type; the possibility of full prohibition has been discarded for fear that colistin might tend to be replaced with fluoroquinolones, an even more dangerous option.
To conclude his intervention, Torren indicated that the new EU legislation applied to antibiotics will make a mutually exclusive separation between medicines that are to be used either on humans and those that are to be used on animals.
The head of the European Food Safety Agency’s BIOCONTAM unit, Ernesto Liébana, provided information about the tasks his organization assumes to help avoid the occurrence of Antimicrobial Resistance (AMR) in the food chain in the European Union – a territory in which, as he pointed out, ad hoc legislation has been successfully implanted, while the level of effective surveillance still needs to be increased. The reduction of resistances to fluoroquinolones likewise remains an urgent priority.
Within the EFSA’s monitoring tasks, Ernesto Liébana highlighted surveillance of the spread of AMR, the estimation of risks, and the establishment of quantifiable measures via biomolecular means.
This speaker lay special emphasis on salmonella resistance, a zoonotic phenomenon observed in foodstuffs during the 2015-2016 period. Levels of resistance were quite high, and the differences between different animal species were notable, particularly between turkeys and chickens. Liébana also mentioned resistances noted in E. Coli and Campylobacter, associated with a massive use of fluoroquinolones.
He also pointed out that the gradient of susceptibility to E. Coli between Northern European and Southern European countries is quite steep: susceptibility is low in Spain (2.9) compared with high scores registered in Nordic countries, where all cases surpass 70. He also referred to intra-European differences regarding extended spectrum beta-lactamases (ESBL’s), and carbapenems in swine and poultry.
Liébana closed his exposé by citing his agency’s “Three-R’s” motto regarding antimicrobials: “reduce” their use, “replace” them whenever possible, and “rethink” the way meat production can be modified to keep the problem in check.
Dominique L. Monnet, the director of the ECDC’s Resistance and Healthcare-Associated Infections Program (ARHAI), began his exposé by stating that his organization is striving to lower the incidence of contagious diseases within Europe – a territory of 31 countries and almost 500,000,000 inhabitants – which, as he sees it, amounts to 500 human stories nipped in the bud in the form of 25,000 deaths per year, many of which are due to one out of five types of multiresistant bacteria and four main types of infection from a potential total of 31. The diseases range from pneumonia to tuberculosis and influenza.
Dominique L. Monnet affirmed that antimicrobial resistance (AMR) affects all echelons of the health assistance sector. It typically manifests itself in various types of agents and causes a plethora of health service problems. The outbreaks, as he described them, occur in livestock holdings, hospitals, and airports, apart from a great multitude of further potential areas, extending to the entire community.
This specialist distinguished among human consumption of antibiotics, which amounts on average to 124 mg/kg, and the use of antimicrobials in animals, which reaches an average level of 152 mg/kg. In the case of poultry (chickens), he pointed out the resistance of Campylobacter jejuni to quinolones and of salmonella to fluoroquinolones in the same type of animal.
He likewise mentioned strains of streptococcus that are resistant to macrolides. In the case of Spain, he specifically referred to the elevated consumption of penicillins and quinolones, as can be ascertained from pharmacy reimbursement data. Doses amount to 23 per day per 1,000 inhabitants: this corresponds to 1.99 units of volume per thousand inhabitants.
Also referring to Spain, the speaker pointed out the high percentage of resistant staphylococcus strains, and, to a lesser degree, of Klebsiella pneumoniae resistant to carbapenem antibiotics. He concluded his talk with a brief description of EPIS, the Epidemic Intelligence Information System.
Cristina Muñoz Madero, the coordinator of PRAN (the Spanish National Antibiotic Resistance Plan), concretely referred to the European strategy to combat AMR within a global framework. During the conference, the goal was to ascertain how all national Spanish agencies and international organizations involved in combatting this serious public health problem could adequately combine their efforts and work together more effectively.
To attain this, she elaborated on the One Health concept in Spain, and on the objectives and results observed in the first JIACRA España report.
The PRAN’s work, as she described it, focused in the 2012-2016 period on mg of antimicrobials per kg of biomass, particularly in terms of sales of antibiotics: cephalosporins, quinolones, macrolides, polymyxines, tetracyclines, beta-lactamases and carbapenems. Resistances were discovered in strains of E. Coli and K. pneumoniae isolated in foodstuffs, animals, and people.
The PRAN’s methods, as Muñoz Madero described them, consisted in selectively applying clinical or epidemiological cut-off points on the basis of data obtained from official and private medical prescriptions. The most elevated consumption of beta-lactamases can be found in primary medical attention to humans, whereas cephalosporins estimated to be in 3rd or 4th generation have emerged in hospitals. In animals, tetracyclines have the highest consumption rate (based on sales data, not on consumption per se), with E. coli resistant to ampicillin and quinolones in poultry, and ampicillin and beta-lactamases in livestock.
Finally, in farm holdings, an 82% reduction in the use of colistin was observed, within the general framework of a 14% reduction in sales of antibiotics for use in animals.
Among the participants in the audience, a microbiologist of the Carlos III Health Institute (ISCIII) alerted his colleagues to the irregular degree of commitment displayed in the battle against AMR in the south of Europe – even in countries such as Greece and Italy that welcome massive numbers of tourists. In the final discussion it was noted that, in Spain, meat sold for consumption is of excellent quality and no antibiotics are added whatsoever.
Acta Sanitaria. LUIS XIMÉNEZ — MADRID 5 JUN, 2018 – 4:54 PM