Antimicrobial Resistance Working Group meeting 9 September 2013

Summary of the first meeting of the group

Terms of reference

1. The group discussed and agreed their role, terms of reference and scope. The group also discussed their workplan for the forthcoming year and identified key documents and issues they wished to review and discuss. The group planned to meet four times a year.

Outstanding recommendations from ACMSF 1999 report on AMR

2. Members reviewed the outstanding recommendations from ACMSF’s 1999 report on Microbial Antibiotic Resistance in Relation to Food Safety and discussed whether these were still relevant. They related to two main areas:

- Gaps in the knowledge base with regards to the prevalence of antibiotic resistance in commensal microorganisms found in food (particularly E. coli and enterococci)
- Gaps in Government funded research on antibiotic-resistance bacteria in imported food and animal feeding stuffs and in the area of microbiological risk assessment.

3. The group noted that 14 years have elapsed since the report had been published and since then a lot of work has been undertaken. This has meant that some of the recommendations may be out of date and in some cases may no longer be applicable. In addition some recommendations may need updating or re-framing, for example in light of developments in newly-developed, genomic sequence-based methods for identifying resistance genes in bacterial populations.

4. The role of commensals has been identified as important in spreading resistance genes to pathogens. This has been highlighted in a 2011 EFSA Opinion on the public health risks of bacterial strains producing extended-spectrum β-lactamases (ESBLs) and/or AmpC β-lactamases in food and food-producing animals and also in a series of recent papers from The Netherlands. When the ACMSF 1999 report was being written, methods for detection of resistance would have relied heavily on phenotypic methods including the use of surrogate markers. There is now increased emphasis on tracking the spread of resistance genes between organisms which has been facilitated by the use of molecular methods. Hazards in this area are posed by the presence of resistance genes, and their propensity to “move” (e.g. plasmid/ integron/transposon versus nucleus) from the current commensal host.

5. In relation to imported foods the group commented that the relative importance of imported foods to the development of AMR is unknown and it remains a potentially significant source. This is particularly relevant in that such foods may be imported from countries where production is cheaper and antibiotic usage in food animals is less regulated than in the UK, and in other EU Member States.

6. Some antimicrobial resistance gene/organism combinations are spread by the food-borne route and have had significant effects in some areas e.g. Salmonella Kentucky in North Africa and Eastern Europe, but not to a significant extent in the UK. Data to understand these patterns and associated risks would be desirable.

7. The new poultry inspection proposals from the Commission include requirements to define the levels of E. coli with ESBLS/AmpC-encoding resistance genes.

8. In summary the group considered that AMR in imported food remains an area of concern, and the knowledge gaps in this area need to be resolved to inform risk management.

9. The working group also considered imported feedstuffs and noted there are differences between bacteria in imported animal feed, and in imported feed that is medicated (including water). It was thought that there is little feed that is imported already medicated, but imported feed may be contaminated with resistant micro-organisms. It was considered that it was important to know whether there is an enhanced risk from imported feed and there is still insufficient data to inform assessment of these risks.

10. In relation to the outstanding, and in some cases longstanding, recommendations re AMR (ACMSF 1999, 2005 & 2007) the group noted that some significant gaps in the knowledge base remain. The working group will continue to monitor and report on these gaps, “new gaps”, and re-opening gaps (i.e. areas where the passage of time, and changes in AMR patterns mean that new/additional data is necessary to inform accurate risk assessment).

European Medicines Agency (EMA) advice on colistin and tigecycline

11. The European Commission submitted a request to the EMA for advice on the impact on public health and animal health of the use of antibiotics in animals. The EMA published an opinion responding to this request on 19th July 2013 focussing their advice on colistin and tigecycline.

12. The working group reviewed the EMA documents. The group noted that, in the UK, colistin is frequently used in livestock (pigs and poultry), sometimes in combination with critically-important antimicrobials such as fluoroquinolones and very occasionally used in humans. In the past colistin was not used in human medicine because of its toxicity and because more effective antibiotics were available. The emergence of resistance to other first-line or last resort antibiotics now means that colistin is, in some circumstances, becoming the only effective appropriate human antimicrobial. Colistin resistance has not been demonstrated to be plasmid-mediated, and there is no evidence of horizontal transfer of the resistance gene to other bacteria associated with its use in livestock. Emergence of resistance has been observed after colistin use in humans, but there is no suggestion of any link between animal use and resistance in human. As mentioned above, colistin is sometimes used in combination with other antimicrobials in treatment of livestock, which may be of concern. It was also noted that there have been some reports of low level colistin resistance in E. coli and/or possibly some Salmonella serovars at non-therapeutic levels. The group agreed that the EMA advice, including removing prophylactic use of colistin in animals and monitoring of off-label use, was proportionate.

13. The group noted that tigecycline is currently unlicensed for use in veterinary medicine, and is therefore not used in the UK. As long as this restriction remains the group considered that this antibiotic should not pose a significant concern.

Quantification of human deaths due to antibiotic use in chicken

14. The Group considered a letter from Collignon et al, published in Emerging Infectious Diseases in August 2013. These authors estimated the number of human deaths and hospital admissions in European countries (including the UK) resulting from the presence of third generation cephalosporin-resistant E.coli in poultry.

15. The authors used a figure from a study in the Netherlands by de Kraker et al (which estimated the number of human infections with cephalosporin-resistant E. coli that could be associated with poultry consumption) to estimate the number of such infections in other European countries. The group expressed concerns over such extrapolation, as there is evidence that:

a) ESBL levels in poultry in The Netherlands are much higher than in the UK
and;

b) cephalosporin usage in The Netherlands was not the same as in the rest of Europe.

16. The working group also noted that a more recent paper by de Kraker et al queried some of the initial research findings. Overall, the group also felt that although some of statements in the letter were currently unsubstantiated, they could usefully be further examined. Members noted that the authors should be commended for attempting a quantitative risk assessment, but felt that uncertainties remained in relation to the validity of the data used to calculate the above estimates, along with potential difficulties around the large confidence intervals associated with the estimates.

DH AMR Strategy

17. The group noted that the DH strategy on AMR was due to be published on 10th September and agreed to provide comments on the strategy. They also noted DH’s intention to produce a draft implementation plan which they would have the opportunity to comment on at a future meeting. Members were updated on some of the groups being established by DH to help with implementing the AMR strategy and it was suggested that ACMSF may be involved/provide advice to one of the implementation groups.