WHAT DO WE KNOW ABOUT AMR & THE FOOD CHAIN ? Martin Cormican, Galway University Hospital and National University of Ireland, Galway
Antimicrobial Resistance and Microbial Ecology Group School of Medicine, NUI Galway
WHAT DO WE KNOW ABOUT THE FOOD CHAIN ? • • • •
Scientific Literature – discontinuous Annual Reports – continuity. Examples
National Reference Laboratory Antimicrobial Resistance (Backweston) • •
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Not enough – Some Sources
National SSL Reference Laboratory (Galway) Health Products Regulatory Authority (HPRA)
The EU Summary Report of antimicrobial resistance in zoonotic and indicator bacteria from humans, animals and food
Antimicrobial Resistance and the Food Chain What We Know •
1. Antimicrobial residues in food appears to be well controlled
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2. Antimicrobial resistant gastrointestinal zoonotic pathogens are detected in food and are transmitted to humans through the food chain (Salmonella, Campylobacter,VTEC)
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3. Antimicrobial resistant organisms other than primary gastrointestinal pathogens (E. coli) are also present in food and probably transmitted through the food chain to some degree.
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4. Good practice (production, processing, storage, cooking) should substantially reduce the risk of transmission of antimicrobial resistant organisms in the food chain
Transmission of Antimicrobial Resistant Gastrointestinal Pathogens – Salmonella spp. •
2013: 345 cases of laboratory confirmed Salmonellosis in Ireland (almost all presumed to be food borne zoonosis)
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44% were resistant to at least one of the panel of antimicrobial agents tested
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30% were multidrug-resistant (3 or more classes)
Transmission of Antimicrobial Resistant Gastrointestinal Pathogens – Salmonella spp. •
How much does this resistance in Salmonella matter ?
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1. It is mainly to older agents (ampicillin, sulfonamide, tetracycline)
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2. Is associated with expansion of specific clonal groups (e.g. ampicillin, streptomycin, sulfonamide, and tetracycline associated with monophasic S. Typhimurium)
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Does it matter much for clinical practice ?
Transmission of Antimicrobial Resistant Gastrointestinal Pathogens – Salmonella spp. •
Probably Yes –
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Pushes us up the ladder for empiric therapy from cotrimoxazole
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We now rely on third generation cephalosporins and fluoroquinolones
Salmonellosis – the agents we depend on now
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Resistance to the agents we rely on – third generation cephalosporins (cefotaxime) and fluoroquinolones (ciprofloxacin)
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7 (2%) Cephalosporin resistant in 2013
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5 Extended-spectrum beta-lactamase producers (ESBL’s)
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[India, Thailand, Morocco, Cuba)
Transmission of Antimicrobial Resistant Gastrointestinal Pathogens – Salmonella spp. •
But you don’t have to travel to find cephalosporin resistant Salmonella (but it may help)
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2013: 2 AmpC producers [not associated with reported travel]
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2009 Extended Spectrum β-lactamase and AmpC producing Salmonella isolated from poultry products in Ireland.
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SHV-12 in 4 of 7 S. Kentucky
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Plasmid mediated AmpC, CMY-2 in 3
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[ But no human infection documented]
Transmission of Antimicrobial Resistant Gastrointestinal Pathogens – Salmonella spp. •
Fluoroquinolones
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2013 5 (1.4%) ciprofloxacin resistant isolates (one S. Typhi)
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S. Kentucky associated with Nepal
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S. Typhimurium associated with Thailand (also ESBL)
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2 Monophasic S. Typhimurium associated with Thailand and China (1 also ESBL)
Transmission of Antimicrobial Resistant Gastrointestinal Pathogens – Salmonella spp. •
Fluoroquinolones Resistance in 2014
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Will be more like 14% than 1.4%
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EUCAST changes to interpretive criteria
Transmission of Antimicrobial Resistant Gastrointestinal Pathogens – Salmonella spp. •
Cephalosporin and Fluoroquinolone Co- Resistance in 2013
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2 of 345 (less than 1%) both associated with Thailand
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[ EU Summary Report Does not really show the same link to Asia very clearly]
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So if human travel to Asia is associated with acquisition of AMR in salmonella what about food travelling to Europe ?
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We don’t have much systematic data to answer this
Transmission of Antimicrobial Resistant Gastrointestinal Pathogens – Salmonella spp. •
What have we got for cepahlosporin and fluoroquinolone resistant Salmonella if they they need treatment ?
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Meropenem* (Azithromycin/Tigecycline)
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Expanded panel of routine testing from 2014
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as per ECDC guidance
Transmission of Antimicrobial Resistant Gastrointestinal Pathogens – Salmonella spp. & Tigecycline •
March 2014 2 cases of S. Typhimurium DT19, two children in a small town in West of Ireland
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Both tigecycline resistant and no history of tigecycline exposure
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Look back: 2000-2013
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Selected 10 Tetracycline-resistant S. Typhimurium per year to include all DT19
Transmission of Antimicrobial Resistant Gastrointestinal Pathogens – Salmonella spp. & Tigecycline 43 out of 140 (31%) non-susceptible to tigecycline 32 were resistant to tigecycline
11 were of intermediate susceptibility 27 of 38 porcine isolates (71%) were non-susceptible
13 of 87 human isolates (14%) were non-susceptible All 3 DT19 isolates (all from porcine sources) were tigecycline resistant.
Transmission of Antimicrobial Resistant Gastrointestinal Pathogens – Salmonella spp. & Tigecycline Twenty of the 43 isolates (47%) were from 2000 to 2005 inclusive before tigecycline was introduced into clnical use What is driving this ? We postulate tetracycline Are we compromising new antimicrobials before we find them ?
Transmission of Antimicrobial Resistant Gastrointestinal Pathogens – Salmonella spp. & Azithromycin
Bovismorbificans
ACSSuTTmNaCpCazGmCtxAztTigCef
>64 mg/l
64mg/l (static) or > 256 (cidal)
Vietnam
Saintpaul
ASSuTAzt
>64 mg/l
192 mg/l (static) or >256 (cidal)
Thailand
Stanley
ACSSuTTmCpAzt
64 mg/l
48 mg/l
Malaysia
Rissen
AAzt
>64 mg/l
128 mg/l
-
Typhimurium
ACSSuTNaCpGmAzt
32 mg/l
? 4/24
-
Transmission of Antimicrobial Resistant Gastrointestinal Pathogens – Salmonella spp. & Tigecycline Meropenem resistance ? Not here yet (in salmonella) France have reported a non-susceptible in S. Kentucky in 2013
Some reports from elsewhere in the world What could be driving this resistance to carbapenems if they are not used in animals ? We are approaching untreatable salmonellas but not there yet
Salmonella in Europe- Human Data
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FDA Risk Assessment
Salmonella In Europe- Food Data.
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FDA Risk Assessment
Campylobacter spp. Human Sources and AMR in Ireland There is no human reference laboratory /no human reference laboratory data There is even less chance of clinical laboratory data in the future than there was in the past (“Enteric Bio”) The revolution in molecular diagnostics of enteric pathogens potentially threatens AMR surveillance
European Data on Campylobacter- Human. •
German Outbreak
VTEC and AMR in Ireland
Not included in the VTEC Reference Laboratory Annual Report No clinical laboratory data to my knowledge (CL3)
Transmission of Antimicrobial Resistant Gastrointestinal Pathogens – 2011 STEC O104 H4.
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ESBL Producer
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Resistant to ampicillin, cefotaxime, ceftazidime, streptomycin, sulfamethoxazole, trimethoprim, tetracycline, nalidixic acid
AMR in Organisms Other then GIT Pathogens.
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Data on AMR in indicator organism (E. coli) from food & animals including
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Likely to be transferred to humans to some degree
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But does it matter? /does it matter very much in the overall context ?
ExPEC e.g Urinary Tract Infection
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Lazarus B et al. Systematic Review CID 2014 Oct 9
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Cephalosporin-resistant Extraintestinal Pathogenic E . coli (ExPEC) infection from animals to humans [Netherlands best data]
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In some other countries this may be relatively less important
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Riley LW. Clinical Microbiol Infect May 2014
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Do the AMR clonal groups spread because they are drug resistant ?
Extraintestinal Pathogenic E. coli (ExPEC) Human – Human Transmission •
Small amount of data on AMR in E. coli from RTE foods
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Essentially all susceptible to all agents tested ?
Antimicrobial Resistance and the Food Chain Major Gaps •
1. Relative importance of the food chain in dissemination of antimicrobial resistant bacteria (may be country specific)
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2. To what extent does the food chain contribute to human to human transmission of AMR E. coli ?
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3. To what extent if any does trade in food contribute to global dissemination of antimicrobial resistance ?
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4. Is the presence of AMR genes in dead organisms in food important in dissemination of AMR ?
Summary of What We Know
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Salmonella resistant to ciprofloxacin and cephalosporins occur but are uncommon
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We are occasionally close to untreatable salmonella (associated with Asia in our experience)
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Our data (in Ireland) on AMR in Campylobacter and STEC (from humans) is much more limited
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Role of food in AMR ExPEC less clear and relative importance may be country dependent
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There are issues with data quality in EU Summary Reports
Summary of What We Know
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Reassuring data on antimicrobial residues
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Data on consumption in food producing animals – scope to improve granularity of data and scope to reduce
Acknowledgements
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Biological Safety Subcommittee FSAI
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AMR Working Group FSAI
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Colleagues in NSSLRL, NUIG and GUH & elsewhere
