4. Friday Monogastric Sessions prof john pluske murdoch university - amr in australia, where are we at

1. Antimicrobial resistance in
Australia: where are we at?
Sam Abraham and John Pluske
Antimicrobial Resistance and Infectious Diseases Laboratory
s.abraham@murdoch.edu.au; J.Pluske@Murdoch.edu.au

2. What is antimicrobial resistance?
• Antimicrobial resistance (AMR) in animals and
humans occurs when antibiotic (antimicrobial)
levels that would normally prevent the growth
of, or kill a, particular bacterium become
ineffective because of a genetic change in that
bacterium
• Continued use of an antimicrobial then allows
resistant bacteria to survive, rather than be
killed

3. (CDC; andWashington Post)
A natural phenomenon accelerated by antimicrobial use
AMR development in bacteria

4. Relationship between total antibiotic
consumption and Streptococcus
pneumoniae resistance to penicillin
in 20 industrialized countries
(Albrich et al., 2004; Emerg. Infect. Dis. 10:3)

5. Antimicrobial use ranking (lowest 1, highest 7)
and antimicrobial resistance ranking
(lowest 1, highest 7) of
indicator Escherichia coli isolates in food-
producing animals
(Chantziaras et al., 2014; J. Antimicrob. Chemother. 69:827–834)

6. Time lag between an antibiotic being
introduced and the first appearance
of resistance; it’s become shorter!
(from Antimicrobial Resistance StandingCommittee, Commonwealth of Australia, 2013)

7. • “But I would like to sound one note of warning. Penicillin is
to all intents and purposes non-poisonous so there is no
need to worry about giving an overdose and poisoning the
patient.There may be a danger, though, in underdosage.
• It is not difficult to make microbes resistant to penicillin in
the laboratory by exposing them to concentrations not
sufficient to kill them, and the same thing has occasionally
happened in the body."
• Sir Alexander Fleming (December 11, 1945; Nobel Prize Award Lecture)
Should we be surprised?

8. (CDC)
Examples of how
antibiotic resistance spreads

9. • High importance (‘last resort’ use): piperacillin (+/-
tazobactam), ticarcillin/clavulanate, 3rd and 4th
generation cephalosporins, carbapenems and
monobactams, vancomycin, linezolid, fluoroquinolones,
streptogramins, anti-TB drugs, colistin, amikacin
• Medium importance: anti-staph penicillins, amoxycillin-
clavulanate, 1st and 2nd generation cephalosporins,
cephamycins, gentamicin/tobramycin, lincosamides,
nitroimidazoles
• Low importance: penicillins/amoxycillin, tetracyclines,
macrolides, neomycin, sulfonamides/trimethoprim,
amphenicols, nitrofurantoin
Critically important antimicrobials
(CIAs): high importance = reduced
use

11. AMR analysis in Australia
• One of the first countries to have adopted AMR risk
analysis as part of regulatory processes for registering
veterinary medicines
• Critically important antimicrobials such as
fluoroquinolones (e.g., ciprofloxacin, moxifloxacin) and
carbapenems (e.g., imipenem) are not permitted to be
used
• Ceftiofur use is also restricted in livestock

12. Where does Australia sit with
AMR in pigs and poultry?

13. Major conclusions
• Study showed that,
• Non-susceptibility (resistance) to first line antimicrobials is common
among E. coli and Salmonella spp. isolates from healthy slaughter
age pigs in Australia
• However, very low levels of non-susceptibility to critically important
antimicrobials (CIAs), namely third generation cephalosporins and
fluoroquinolones, e.g., ciprofloxacin, were observed
• The isolation of two ciprofloxacin-resistant E. coli isolates from
Australian pigs demonstrates that even in the absence of local
antimicrobial selection pressure, fluoroquinolone-resistant E. coli
clonal lineages may enter livestock production facilities despite
strict biosecurity

14. Animal use of antimicrobials in
Australia

15. Porcine ETEC:
• No carbapenem (), ESCs (extended spectrum cephalosporins) or FQ (fluoroquinolone)
resistance
• Australian isolates are different to the rest of the world
• Multidrug-resistance to beta-lactams (e.g., penicillin), tetracycline, SXT
(trimethoprim/sulfamethoxazole) and aminoglycosides (e.g., neomycin) is common

16. Livestock - Salmonella enterica:
• Low level of resistance in general
• No carbapenem, ESCs or FQ resistance

17. Salmonella enterica from eggs:
• Low level of resistance in general
• No carbapenem, ESCs or FQ resistance

19. Amoxicillin - for S. suis
Lincomycin – use as required
Kitasamycin - for ileitis and Erysipelas
2013 2014 2015 2016
Sampling / methods
Ceftiofur for E.
coli scours
Carriage of ESCR E. coli continues
even after use stops
(Abraham et al., 2018; The ISMEJournal)

20. Carriage of ESCR E. coli continues
even after use stops
n=90 n=60 n=140 n=200
86.6%
83.3%
22.1%
8.5%
0.0%
20.0%
40.0%
60.0%
80.0%
100.0%
2013 2014 2015 2016
Withdrawal of ESC
Pigs in different stages of production
were positive
ESC = extended spectrum cephalosporin (ceftiofur) (Abraham et al., 2018; The ISMEJournal)
Non susceptibility

21. Carbapenem resistance in
Salmonella from cats and
seagulls
(Doljeska et al., 2015 JAC)

22. AMR – Biosecurity issue

23. Where to from here for AMR?
• We are starting from a very good base
• Development of robust ‘One Health’ antimicrobial prudent use guidelines
• Use of effective diagnostics and continuous infection control and biosecurity are
critical
• AMR surveillance
• Education and stakeholder engagement
• Alternatives to traditional antimicrobials
eg: autogenous vaccines, selected feed additives

24. APRIL-funded project; 2018-2020
• APRIL - Australasian Pork Research Institute Ltd.
• (New) Member-contribution company transitioned from the Pork
Cooperative Research Centre, that will continue research and
development in the Australasian pork industry
• Novel approaches for reducing antimicrobial resistant and
pathogenic Gram-negative bacteria in the porcine gut
• Murdoch University, Feedworks, University of Adelaide

25. Novel approaches for reducing
antimicrobial resistant and
pathogenic Gram-negative
bacteria in the porcine gut
BROAD AIMS:
• To analyse the potential translation to the pig industry of
specialised dried yeast ferments and lactobacillus ferments, for
which published results outline the inhibition of virulence, faecal
shedding and antibiotic resistance of Salmonella in poultry (Feye et
al., 2016)
• To develop a novel ‘cocktail’ of susceptible, non-virulent porcine gut
bacteria (biotherapeutics) and applying the same analytics

26. Novel approaches for reducing
antimicrobial resistant and
pathogenic Gram-negative bacteria
in the porcine gut
• Experimental aims:
• Evaluate effects of specialised dried yeast ferments and specialised dried
lactobacillus ferments in reducing the severity of ETEC infections in post-
weaned pigs
• Evaluate effects of specialised dried yeast ferments and specialised dried
lactobacillus ferments in reducing resistant bacteria, focusing on CIAs, in the
post-weaned pig gut
• Evaluate impact of specialised dried yeast ferments and specialised dried
lactobacillus ferments on overall performance and indices of gut health in post-
weaned pigs
• Evaluate effects of novel gut-biota, culture-based biotherapeutics to decrease
overall Gram-negative resistant bacteria in the gut and improve gut health and
production outcomes

29. Methodology
• Experiment 1a): ETEC challenge trial to evaluate effect of specialised
dried yeast ferments and lactobacillus ferments on ETEC clinical
disease and shedding, and aspects of gut health and the microbiome
• Experiment 1b): CIA resistant E. coli trial – weaners shedding CIA
resistant E. coli treated with specialised dried yeast ferments and
lactobacillus ferments to determine effect on shedding
• Experiment 2a) ETEC challenge trial to evaluate effect of specialised
biotherapeutics (bacteria) on ETEC clinical disease and shedding, and
aspects of gut health and the microbiome
• Experiment 2b) CIA resistant E. coli trial – weaners shedding CIA
resistant E. coli treated with specialised biotherapeutics (bacteria) to
determine effect on shedding and reversion to susceptible gut biota
• Experiment 3) Field trial (at base funded facility) to validate outputs
from Experiments 1 and 2