Reduction of antibiotic use in animals “let’s go Dutch”
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KeywordsColistin Livestock Production Methicillin Resistant Staphylococcus Aureus Sales Data Veal Calf
Use of antibiotics for animals in the Netherlands has reduced considerably over the last 5 years. This reduction is the result of a change in policy towards the use of antibiotics in veterinary practice and is characterized by a series of coherent political decisions which changed the playing field for farmers and veterinarians considerably. In the years before the reducing trend in use of antibiotics started off, the Netherlands was a relative high consumer of antibiotics in veterinary practice. The trends in antibiotic use will be explored in this paper, in particular focussing on the reducing trends in recent years, and the measures which led to the strong reducing trend which can be observed over a period of more than 3 years now.
2 The years of high use of antibiotics in livestock production
Apparently, systematic use of cheap antibiotics was considered more cost effective for intensive animal production, than implementing stringent health and infection control programs. Moreover, the control on prudent antibiotic use was insufficient until 2008.
Based on these sales data, the European Surveillance of Antibiotic Use working group (ESVAC) of the European Medicine Agency in London reported in 2012 that in the Netherlands most antibiotics were used per kg live weight produced (Grave et al. 2012).
3 Prudent use of antibiotics in human medicine in the Netherlands
In contrast, in Dutch human medicine, use of antibiotics can be considered as essentially prudented. In patients in the Netherlands, antibiotic use is among the lowest of Europe (Elseviers et al. 2007; Vander Stichele et al. 2006). As a result microbial resistance levels in health care are low, as illustrated by the low level of Methicillin Resistant Staphylococcus aureus (MRSA) infections. These occur only incidentally in invasive infections in hospitals (EARSNET-20131). Also the occurrence of cefotaxime resistant isolates suspected to produce Extended Spectrum Beta-Lactamases (ESBLs) in infections in hospitals, is lower than in most other European countries (EARSNET-2013). This enormous contrast in antibiotic use in veterinary and human medicine practice feeds the negative perception of medical doctors, authorities and the public about live-stock production in the Netherlands. Moreover, the consequence is also that any potential contribution of resistant organisms from animals to human infections in health care is more visible in routine statistics and has a higher potential contribution to disease load than in countries with high usage in human health care and with endemic occurrence of multi-drug resistant organisms in hospitals.
A result of the high use of antibiotics in animals, is that resistance levels are high in food-producing animals as reported in the annual reports of the Dutch Monitoring of Antibiotics use and Resistance in Animals program (Anonymous 2013). Resistance levels are most optimally measured in the intestinal flora of healthy animals (Anonymous 2008). Commensal E. coli isolated according to EFSA protocols is used as indicator organism of the Gram-negative intestinal flora. Multi-drug resistance levels in E. coli are high and increased up to 2009 in isolates from broilers, pigs, and veal calves and to a lesser extend in those from dairy cattle (Anonymous 2008). This indicates that the gastro-intestinal tract of food-animals is a (potential) reservoir of multi-drug resistant organisms.
4 Events leading to increased attention for high veterinary use of antimicrobials
Livestock MRSA (ST398) was first detected in a Dutch pig farm in 2005 (Voss et al. 2005). Surveillance targeted at MRSA prevalence showed that most pig and veal calf farms are positive for MRSA, and that this organism can also be found in companion animals, horses, poultry and meat products.2 The transmission route of MRSA to humans is direct contact, and farmers and veterinarians are considered to be at risk to be MRSA carriers (Dorado-Garcia et al. 2013; Gilbert et al. 2012; Graveland et al. 2011). Patients at risk to carry MRSA are nursed and treated in isolation in hospitals to prevent spread of MRSA (Voss 2004; Wassenberg et al. 2010). The frequent occurrence of MRSA ST398 has resulted in human infections, although MRSA ST398 is generally not considered a highly pathogenic micro-organism, but in particular had a major effect on increased costs in health care, which has increased the level of concern of health care authorities regarding Dutch livestock production. The emergence of MRSA was paralleled by occurrence of ESBL-producing organisms in livestock production. Since 2002 the occurrence of ESBL-producing organisms has been observed in broilers (Dierikx et al. 2010). Both in E. coli and in Salmonella a rapid increase was observed of ESBL-producers in these animals. A prevalence study showed that all broiler farms were positive and virtually all animals shed ESBL-producing E. coli in their faeces (Dierikx et al. 2013). As a result almost all broiler meat products were positive for ESBL-producing organisms (Cohen Stuart et al. 2012; Overdevest et al. 2011). A large study conducted with the University Medical Centre of Utrecht (UMCU) and the Dutch Institute for Public Health and the Environment (RIVM) showed that one in five human clinical ESBL-producing isolates harboured genes and plasmids that seemed indistinguishable from poultry genes and plasmids (Leverstein-van Hall et al. 2011). Poultry meat was considered a potentially likely route of transmission to humans. Data from poultry sources and from subsequent screening in other food-animals, dogs and wild birds demonstrating high prevalences further raised concerns about the possible attribution of ESBLs from animal related sources to infections in humans.
5 Reducing the use of antimicrobials in veterinary practice
An essential element in the approach of the task force was to make antibiotic use on all farms transparent. Since 2012 it is mandatory to register all antibiotics supplied by veterinarians. This was already partially implemented by the private stakeholders in animal production in 2011 in veal calves, broilers and pigs as part of their quality systems. In particular by means of the quality systems acting at the sector level, they were able to implement these policies swiftly and effectively. In 2012 cattle followed. Usage on farms is expressed as animal daily dosages per year (add/y) (Bos et al. 2013), which resembles the Danish system of reporting.3 In this way farms and vets can be benchmarked and compared with each other and with independently defined targets (benchmarking). An essential part of this process was to install an independent institute to control the use data, report the data publically and to define targets for use. In spring 2011 the Netherlands Veterinary Medicines Authority (SDa: www.autoriteitdiergeneesmiddelen.nl) was installed for this purpose and the first targets for use in different animal production sectors were published in July 2011.
Because of the concerns about MRSA and ESBLs in food-animals, the Dutch Heath Council was asked to advice the Ministers of Public health Welfare and Sports and the Minister of Economic Affairs about antibiotic usage in animals. The advice included a full ban in usage of any new antibacterial drug in animals and a restriction of the use of 3rd and 4th generation cephalosporins in animals. Moreover, it was advised to restrict the use of colistin, all beta-lactams, aminoglycosides and fluoroquinolones in food-animals. Since this advice lacked detail, the Antibiotics Policy Working Group (WVAB) of the KNMvD, wrote a guideline in which drugs were classified as first, second and third choice drugs for inclusion in treatment plans on farms (http://wvab.knmvd.nl/wvab). Moreover, the animal drug law was changed in 2013, ruling that only first choice drugs are allowed to be present on farms for empiric treatment of infections based on a mandatory treatment plan for each farm. This treatment plan has to be custom made by the veterinarian for each farm, based on treatment guidelines of the KNMvD (formularia: http://wvab.knmvd.nl/wvab/formularia/formularia).
In 2013 the SDa has defined quantitative reduction targets for antibiotic use for each food-animal species (in add/y) including zero add/y as quantitative target for fluoroquinolones and 3rd, and 4th generation cephalosporins. The latter two drugs are only allowed after it has been proven that no alternative treatment options are available. This is also regulated in 2013 by the change in the animal drug law. In the meantime, most animal production sectors have voluntarily decided to stop usage of these third choice drugs in animals on a voluntary basis.
However, to solve the current and future threats of multi-drug resistant organisms in (food)-animals to human health, a substantial further reduction may be warranted and on the longer term a change in animal production practices cannot be excluded. In 2014 next to livestock farms, veterinarians will also be benchmarked. A system has been developed which describes the use of antimicrobials on the population of farms for which a veterinarian is responsible. To facilitate this approach, regulations were put in place which resulted in unique one on one relations between veterinarians and livestock farmers. Further refinements in the benchmarking system are to be expected.
European Centre for Disease Prevention and Control. Antimicrobial resistance surveillance in Europe 2012. Annual Report of the European Antimicrobial Resistance Surveillance Network (EARS-Net). Stockholm: ECDC; 2013. http://www.ecdc.europa.eu/en/healthtopics/antimicrobial_resistance/database/Pages/map_reports.aspx.
Analysis of the baseline survey on the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in holdings with breeding pigs, in the EU, 2008, Part A: MRSA prevalence estimates; on request from the European Commission. EFSA Journal 2009; 7(11):1376 [82 pp.]. doi: 10.2903/j.efsa.2009.1376. Available online: www.efsa.europa.eu.
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