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Resistance calls for changes in practice

Livestock producers in the Netherlands are forced to reduce the use of antibiotics by 70% by 2013. These reductions in antibiotic use and changes in livestock production practices are warranted. Major steps have been made already to meet this goal by making the use of antibiotics on all farms transparent.

By Prof Dr Dik Mevius, Dept of Bacteriology and TSEs, Central Veterinary Institute of Wageningen UR, Lelystad; Department of Infectious Diseases and Immunology, Utrecht University; Veterinary Drug Authority, Utrecht, the Netherlands

In the Netherlands antibiotic usage in animals is usually derived from sales data of Fidin, the Organised Dutch Veterinary Pharmaceutical Companies. These sales data are considered to provide a good estimate for antibiotic usage in animals on prescription by veterinarians. However, specification by animal species is not possible, since many products are licensed to be used in multiple animal species. Sales of antibiotics in the Netherlands increased from 300 tonnes in 1999 to almost 600 tonnes in 2007. However, in that period the use of antimicrobial growth promoters was reduced from 250 tonnes in 1998 to zero in 2006, which is the result of the ban on these substances by the European Commission. Since the number of livestock produced did not change that much, the sales data indicate that the standard antimicrobial growth promoters were in equal amount replaced by antibiotic substances prescribed by veterinarians.

Low usage – high impact
Based on the Fidin sales data, the European Surveillance of Antibiotic Use working group (ESVAC), of the European Medicine Agency in London reported that The Netherlands is using the most antibiotics in animals per kg live weight produced. In human medicine in the Netherlands the use of antibiotics is very restricted; in outpatients antibiotic use is among the lowest in Europe.

As a result resistance levels in health care are low. Methicillin resistant Staphylococcus aureus (MRSA) infections occur only incidentally in hospitals. 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.

This apparent contradiction in antibiotic usage, feeds the perception of medical doctors, authorities and the public about livestock production. The consequence is that any potential contribution of resistant organisms from animals to humans has a higher impact here than in countries with a high usage in human health care.

Reservoir of resistant organisms
As a result of high usage of antibiotics in animals, the 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 (Maran). Resistance levels are measured optimally in the intestinal flora of healthy animals. According to protocols of the European Food Safety Authority, isolated commensal E. coli’s are used as indicator organism of the gram-negative flora. It is proven that resistance levels in E. coli are high and increasing in isolates from broilers, pigs and veal calves and to a lesser extent from dairy cattle. This indicates that food animals act as a reservoir of multidrug resistant organisms.

In 2005 livestock MRSA (ST398) was first detected in a Dutch pig farm. A more recent 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. Given that the transmission route to humans is direct contact, farmers and vets are considered to be MRSA carriers be a risk to human health. To prevent the spread of MRSA patients at risk to carry MRSA are nursed and treated in hospitals in isolation. The frequent occurrence of MRSA ST398 in animals and consequently more human infections has a major effect the costs in human health care. This increased the level of concern of health care authorities towards the role of antibiotic use in the Dutch livestock production.

Since 2002 the occurrence of ESBL-producing organisms has been observed in poultry. Both in E. coli and in Salmonella a rapid increase was observed 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. As a result almost all broiler meat products are considered to be positive for ESBLs.

A large study conducted by 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 are indisguisable from poultry genes and plasmids. This made poultry meat the most likely route of transmission to humans.

Dramatic reduction needed
The concerns about public health consequences of antibiotic usage and resistant organisms in animals to human health have resulted in changes in the policy of the authorities. Already in 2008 the Dutch minister of Agriculture, Nature and Food quality, installed a task Force on Antimicrobial Resistance in Food Animals and forced the combined animal production sectors and the Veterinary Association (KNMvD) to sign memos of understanding, which describes measures to reduce antibiotic use and resistance. In 2010, after discussions in parliament about ESBLs in poultry, mandatory reduction targets in usage were defined  as 20% reduction by 2011 and 50% by 2013. In 2012 this target was renewed to 70% reduction.

An essential part of the approach was to make the use of antibiotics on all farms transparent. All antibiotics supplied by vets must be registered. In the course of 2011 the new rules were implemented for veal calf, broiler and pig production and in 2012 cattle would follow. The use on farms is expressed as animal daily dosages per year (add/y), which mimics the Danish system of reporting. By doing this farms and vets can be benchmarked and compared. An essential part of this registration process is the installing of an independent institute to define targets for usage. In spring 2011 the Veterinary Drug Authority was installed for this purpose and the fist targets were published in July 2011.

Time for change
Due to concerns about MRSA and ESBLs in food-animals, the Dutch Health Council was asked to advise the minister of Public Health, Welfare and Sports about antibiotic usage in animals. The advice included a full ban in usage of any new drugs in animals and a restriction of the use of third and fourth generation cephalosporins in animals. Moreover, it was advised to restrict the use of colistin, all betalactams, aminoglycosides and fluoroquinolones in food-animals. Since this advice lacked the necessary 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. The Veterinary Drug Authority will define before quantitative reduction targets per animals species (in add/y) including quantitative targets for thirdchoice drugs. In the mean time, most animal production sectors have decided to stop usage of third choice drugs in animals.

As a result of all these measures taken, sales of antibiotics have dropped in 2012 by 66% since 2007; in addition, the 20% reduction target was reached in 2011. These results can be considered major achievements of private initiatives of the various food animal production industries and the Dutch Veterinary Association, with support of the Dutch government. However, to solve the current and future threats of multi-drug resistant organisms in (food) animals to human health, a substantial further reduction is warranted. On the longer term this major change in animal production practices is needed.