W DO WE KNOW ABOUT AMR & THE F C Martin Cormican What... · Summary of What We Know • Salmonella...

Antimicrobial Resistance and Microbial Ecology Group School of Medicine, NUI Galway

WHAT DO WE KNOW ABOUT AMR & THE FOOD CHAIN ?

Martin Cormican, Galway University Hospital and National University of Ireland, Galway

WHAT DO WE KNOW ABOUT THE FOOD CHAIN ?

• Not enough – Some Sources

• Scientific Literature – discontinuous

• Annual Reports – continuity. Examples

• National Reference Laboratory Antimicrobial Resistance

(Backweston)

• 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

• 2. Antimicrobial resistant gastrointestinal zoonotic pathogens

are detected in food and are transmitted to humans through

the food chain (Salmonella, Campylobacter,VTEC)

• 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.

• 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)

• 44% were resistant to at least one of the panel of

antimicrobial agents tested

• 30% were multidrug-resistant (3 or more classes)



• How much does this resistance in Salmonella matter ?

• 1. It is mainly to older agents (ampicillin, sulfonamide,

tetracycline)

• 2. Is associated with expansion of specific clonal groups (e.g.

ampicillin, streptomycin, sulfonamide, and tetracycline

associated with monophasic S. Typhimurium)

• Does it matter much for clinical practice ?



• Probably Yes –

• Pushes us up the ladder for empiric therapy from co-

trimoxazole

• We now rely on third generation cephalosporins and

fluoroquinolones

Salmonellosis – the agents we depend on now

• Resistance to the agents we rely on – third generation

cephalosporins (cefotaxime) and fluoroquinolones

(ciprofloxacin)

• 7 (2%) Cephalosporin resistant in 2013

• 5 Extended-spectrum beta-lactamase producers (ESBL’s)

• [India, Thailand, Morocco, Cuba)



• But you don’t have to travel to find cephalosporin resistant

Salmonella (but it may help)

• 2013: 2 AmpC producers [not associated with reported travel]

• 2009 Extended Spectrum β-lactamase and AmpC producing

Salmonella isolated from poultry products in Ireland.

• SHV-12 in 4 of 7 S. Kentucky

• Plasmid mediated AmpC, CMY-2 in 3

• [ But no human infection documented]



• Fluoroquinolones

• 2013 5 (1.4%) ciprofloxacin resistant isolates (one S. Typhi)

• S. Kentucky associated with Nepal

• S. Typhimurium associated with Thailand (also ESBL)

• 2 Monophasic S. Typhimurium associated with Thailand and

China (1 also ESBL)



• Fluoroquinolones Resistance in 2014

• Will be more like 14% than 1.4%

• EUCAST changes to interpretive criteria



• Cephalosporin and Fluoroquinolone Co- Resistance in 2013

• 2 of 345 (less than 1%) both associated with Thailand

• [ EU Summary Report Does not really show the same link to

Asia very clearly]

• So if human travel to Asia is associated with acquisition of

AMR in salmonella what about food travelling to Europe ?

• We don’t have much systematic data to answer this



• What have we got for cepahlosporin and fluoroquinolone

resistant Salmonella if they they need treatment ?

• Meropenem* (Azithromycin/Tigecycline)

• Expanded panel of routine testing from 2014

• 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

• Both tigecycline resistant and no history of tigecycline

exposure

• Look back: 2000-2013

• Selected 10 Tetracycline-resistant S. Typhimurium per year to

include all DT19


Pathogens –


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.


Pathogens –


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 ?


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 -


Pathogens –


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

• FDA Risk Assessment

Salmonella In Europe- Food Data.

• 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)


Gastrointestinal Pathogens – 2011 STEC O104 H4.

• ESBL Producer

• Resistant to ampicillin, cefotaxime, ceftazidime, streptomycin,

sulfamethoxazole, trimethoprim, tetracycline, nalidixic acid

AMR in Organisms Other then GIT Pathogens.

• Data on AMR in indicator organism (E. coli) from food &

animals including

• Likely to be transferred to humans to some degree

• But does it matter? /does it matter very much in the overall

context ?

ExPEC e.g Urinary Tract Infection

• Lazarus B et al. Systematic Review CID 2014 Oct 9

• Cephalosporin-resistant Extraintestinal Pathogenic E . coli

(ExPEC) infection from animals to humans [Netherlands best

data]

• In some other countries this may be relatively less important

• Riley LW. Clinical Microbiol Infect May 2014

• 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

• 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)

• 2. To what extent does the food chain contribute to human to

human transmission of AMR E. coli ?

• 3. To what extent if any does trade in food contribute to global

dissemination of antimicrobial resistance ?

• 4. Is the presence of AMR genes in dead organisms in food

important in dissemination of AMR ?

Summary of What We Know

• Salmonella resistant to ciprofloxacin and cephalosporins occur

but are uncommon

• We are occasionally close to untreatable salmonella

(associated with Asia in our experience)

• Our data (in Ireland) on AMR in Campylobacter and STEC

(from humans) is much more limited

• Role of food in AMR ExPEC less clear and relative

importance may be country dependent

• There are issues with data quality in EU Summary Reports

Summary of What We Know

• Reassuring data on antimicrobial residues

• Data on consumption in food producing animals – scope to

improve granularity of data and scope to reduce

Acknowledgements

• Biological Safety Subcommittee FSAI

• AMR Working Group FSAI

• Colleagues in NSSLRL, NUIG and GUH & elsewhere

W DO WE KNOW ABOUT AMR & THE F C Martin Cormican What... · Summary of What We Know • Salmonella...

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