EC Workshop on scientific advice from AMEG

Transcription

1 EC Workshop on scientific advice from AMEG Brussels, 26 Nov 2015 Session 2: Antibiotic Categorisation AMEG Q2 Karolina Törneke / Helen Jukes Liability disclaimer: The views or positions expressed in this presentation do not necessarily represent in legal terms the official position of the European Commission. The European Commission assumes no responsibility or liability with regard to the contents of this document

2 The most critically important Advice on classes or groups of antibiotics ranked according to their relative importance for their use in human medicine, in particular considering whether these antibiotics are essential to treat multidrug-resistant infections in humans in the EU. The Agency should take into account the existing work of the WHO on critical antibiotics and consider the need, advantages, disadvantages and feasibility of categorising antibiotics as for example first line, second line or last resort antibiotics.

3 WHO list of highly/critically important antimicrobials EU is a part of the world and we travel If it s important to the world it s important to us! Criterion 1. Antimicrobial agents used as sole therapy or one of few alternatives to treat serious human disease Criterion 2: Antimicrobial agents used to treat diseases caused by either: (1) organisms that may be transmitted via non-human sources or (2) diseases caused by organisms that may acquire resistance genes from non-human sources.

4 Identification of hazards with zoonotic potential Enterobacteriaceae Enterococcus spp. MRSA Campylobacter spp (Brucella spp)

5 Exposure assessment Could WHO criterion 2 be further developed to allow ranking by estimation of the risk for transfer of resistance from animals to man?

6 An attempt to estimate risk for transfer

7 High or low probability for spread? Vertical transmission? Horizontal transmission? Potential for co-selection? Is there evidence of similarity of bacteria/genes present in animals and bacteria causing resistant infections in humans?

8 The end of a long chain of events

9 The categorisation does not build on a full risk assessment Hazard identification Primarily enterobacteriacae Release assessment Epidemiology of animal disease, posology, PK/PD etc not covered Exposure assessment High or low risk for transfer

10 Category 1 lower risk level to public health e.g. narrow-spectrum Penicillins, Macrolides, Tetracyclines, Polymixins General responsible use principles apply: No unnecessary use Treatment duration limited to that necessary to treat disease Limit group treatments

11 Category 2 higher risk level to public health Fluoroquinolones 3 rd / 4 th Gen Cephalosporins (systemic)? Aminoglycosides? Extended-spectrum penicillins active vs. Enterobacteriaceae Use should be restricted: Should only be used where there are no alternatives

12 Category 3 Antimicrobials not currently authorised for use in veterinary medicine Identified hazard and risk for transfer high: Use in veterinary medicine should be kept at an absolute minimum due to high risk for spread of resistance No identified hazard and/or risk for transfer low: No specific concern identified yet

13 Update on actions taken

14 Category 1 lower risk: CVMP actions CVMP has completed referrals for oral Colistin and Tylosin products Continued focus on responsible use principles in the SPC/product information

15 Category 2 higher risk: CVMP actions Aminoglycosides Possible candidate for category 2: Zoonotic hazard: Enterococcus, Enterobacteriaceae Probability of AMR transfer: High (AMEG Table 3) Categorisation to be considered further as part of fuller risk profiling: CVMP/AWP draft Reflection paper Use of Aminoglycosides in the EU: Development of AMR and impact on human and animal health 1 1 Concept paper EMA/CVMP/158821/2014

16 Aminoglycosides contd. Important in veterinary medicine for a broad range of infections: septicaemias, digestive/ urinary/ respiratory tract, mastitis, Pseudomonas Aminoglycosides make up 3.7% of total sales (mg/pcu) of antimicrobials for food animals. Sales for animal use = 5.2 mg/pcu; human use = 0.2 mg/pcu (ESVAC, 2013 data; JIACRA, 2012 data) AMR: Streptomycin-R in E coli and Enterococcus spp from broilers and pigs is high; Gentamicin-R is generally low (EFSA/ECDC Zoonoses report, 2013 data) CVMP/AWP Reflection paper will examine more closely: Uses in human and vet medicine One Health Mechanisms of resistance Occurrence of AMR in bacteria of human and animal origin and possibility of any link Impacts of AMR on human and animal health CVMP will make recommendations

17 Category 2 higher risk: CVMP actions Extended-spectrum penicillins Aminopenicillins (amoxicillin, ampicillin) and combinations with β- lactamase inhibitors May select Enterobacteriaceae with resistance genes enabling production of β-lactamase enzymes (e.g. ESBLs) which often confer resistance to several other important classes (e.g. cephalosporins) Possible candidate for category 2: Zoonotic hazard: Enterococcus, Enterobacteriaceae Probability of AMR transfer: High (AMEG Table 3) Categorisation to be considered further as part of fuller risk profiling

18 Extended-spectrum penicillins contd. CVMP/AWP Concept paper Use of Extended-spectrum Penicillins in the EU: Development of AMR and impact on human and animal health 2 Important in veterinary medicine to treat septicaemias, respiratory/ urinary tract infections, mastitis Penicillins (all) made up 24.5% of total sales of antimicrobials for food animals; more than half is extendedspectrum penicillins. Sales of all penicillins for human use = 73 mg/pcu; animal use = 32 mg/pcu (ESVAC, 2013 data; JIACRA, 2012 data) AMR: Ampicillin-R is commonly detected in Salmonella and E coli from poultry, pigs and cattle (EFSA/ECDC Zoonoses report, 2013 data) CVMP will consider to develop a reflection paper on this topic and make recommendations 2 EMA/CVMP/AWP/37203/2015

19 Category 3 Antimicrobials not currently authorised for use in veterinary medicine e.g. Carbapenems, Glycopeptides, Monobactams Provisions in the proposed Regulation on Veterinary Medicinal Products: A marketing authorisation for an antimicrobial VMP shall be refused if the antimicrobial is reserved for treatment of certain infections in humans Cascade for antimicrobials: The Commission may.establish a list of antimicrobial medicinal products that cannot be used or which can only be used subject to certain conditions

20 How to use the categorisation? This categorisation may be considered as one element when deciding on when/whether to use a certain class/compound in veterinary medicine but may not be used as the sole base when creating treatment guidelines or when deciding on risk mitigation activities. This categorisation does not directly translate into a treatment guideline for veterinary medicine.

21 Consequences for treatment guidelines treatment guidelines should be on indication level considering also the route of administration, posology and PK/PD be locally developed and implemented rather than at EU level no recommendation whether a certain class/compound should be first line, second line, etc., for a certain species and indication can be given based on this categorisation alone

22 Points for discussion How could the AMEG s categorisation of compounds/classes be used: (a) by regulators when approving, restricting or refusing approval for VMPs (b) by regulators when deciding if there is a need to restrict use of products under the Cascade (c) by experts developing treatment guidelines (d) by veterinarians when making prescribing decisions for approved VMPs and products available via the Cascade.