Download Antimicrobial Resistance (no superbugs but dumb people

Antimicrobial Resistance
(no superbugs but dumb people)
@healthfromenvir
Martin Cormican, Centre for Health from Environment
Ryan Institute, National University of Ireland, Galway
Antimicrobial Resistance and Microbial Ecology Group
School of Medicine, NUI Galway
What Is the Cause of the Problem ?
In A Tweet
Microbial world is a gene cloud
• Genes drift
• Bacteria transform
• Some transform to resistance
• Our choices make resistance a winner
•
What Are the Solutions ?
Tweet 2
• Surveillance
• Targets
• Incentives
• Penalties
• Education & Training & Guidelines are only of
value in preparing stakeholders to accept controls
The Talk in In Pictures: Antimicrobial
Resistance
4
One Health
•
OIE endorses the “One Health” approach as a collaborative and
all-encompassing way to address, when relevant, animal and public
health globally
People
•
Animals
PrGWS K – N. Galway
Groundwater/Stream
PrGWS C – E. Galway
Spring Well
~ 115 Houses
~ 277 Houses
PrGWS M – N.E. Galway
Spring Well
~ 354 Houses
Rural Water
Supplies
Antimicrobial Resistance:
We Are Not Always Blaming Vets
Charles Darwin
Antimicrobial-Resistance & Theory of Evolution
8
Finches
Darwins work based
on form of the
animal (phenotype)
in the days before
DNA analysis
(genotype)
9
What is a Species ?
The Orderly World of Zoology
•Male & Female Can Mate and Produce Fertile Offspring
•DNA (genotype) is transmitted vertically from parent to offspring
•DNA sequences don’t generally wander about between species
•Gradual step-wise changes in genotype & associated change in
phenotype (evolutionay time scale is centuries /millenia)
10
What is a Species ?
The Chaotic World of Bacteria
•
Bacteria that group together as relatively similar to each other
in terms of pehnotype & genotype (DNA sequence) are called a
species
•
The boundary between one species & anohter is somewhat
arbitrary
•
DNA is transmitted vertically from mother to daughter cell
•
DNA sequences also wander about all over the place
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The Microbial Gene Cloud
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The Microbial Gene Information Cloud
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What is a Species ?
The Chaotic World of Bacteria
•
Major changes in genotype may happen rarely in terms of per
number of organisms (e.g. 10-20) but this may still be
frequently in time (because there are so many)
•
Most major changes in genotype are lethal but that does not
matter as the loss is almost immediately replaced (1 cell
becomes 2 in 20 minutes)
•
Some major genotype changes by chance will make a bacteria
that is wholly or partly resistant to some family of
antimicrobial agent
14
Antimicrobial Agents : Flemings Mould
•
Antimicrobial agents have always
existed in the environment e.g. soil &
water
•
Bacteria that could survive in
presence of these tend to take over in
that setting
•
Natural Selection: Many
Environmental Bacteria Tend to Be
Antibiotic Resistant
•
Intrinsic Resistance
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Intrinsic Resistance
•
Pseudomonas aeruginosa
•
When Fleming discovered penicillin Pseudomonas aeruginosa
was already resistant
•
Also resistant to many other antibiotics
•
Rarely cause infection (unless already sick)
•
Similar issues with Acinetobacter species.
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Pathogens Were Generally Susceptible to
Antimicrobial Agents. Why ?
•
Penicillium mould does not grow
in living people or animsals
17
Pathogens Were Generally Susceptible to
Antimicrobial Agents. Why ?
•
Obligate commensals and
pathogens grow in animal /human
host
•
Little exposure to antimicrobial
agents
•
Little selection pressure to favor
bacteria with resistance genes
•
If a E. coli picked up a resistance
it would not do it any and may be
a dead weight gene
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Acquired Resistance in Originally Susceptible
Bacteria
• The era of therapeutic antimicrobial use
• Intense selection pressure on bacteria of
animals /humans
• The regular E. coli die
• E. coli variants with resistance gene surive
multiply & spread
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What Makes a Good Therapeutic Antimicrobial
?
• A useful therapeutic antimicrobial
• A) stop/kill bacteria
• B) not harme the host (people & animals)
• Act at specific biological targets that are
present and important in target bacteria but
absent or not important in host
20
The Antimicrobial Class Concept
• Similar chemical compounds usually act at the
same target or targets
• e.g. all penicillins & all cephalosporins have
common chemical motif & all act on enzymes
that are important in buidling the bacterial cell
wall
21
The Antimicrobial Class Concept
• Changes in the specific target that reduce
vulnerability to any member of a class tends to
result in loss of vulnerability to many or all
antimicrobials in that class (e.g. Penicillins)
• Enzymes that inactivate one member of the
class often inactivate several/many or all
members of the class.
22
The Class Concept & Regulatory
Pharmaceutical Guff
• Licensing & Promotion of one fluoroquinolone
in animals and a different one in human
23
We Understand Acquired Antimicrobial
Resistance
•
Well understood, entirely predictable and probably
inevitable consequence of antibiotic use
•
A consequence of inappropriate use and of appropriate
use
•
A consequence of use no matter who
prescribes/consumes them or for whatever purpose
•
But overuse and irrational use makes it happen faster
and for no corresponding benefit
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Acquired Antibiotic Resistance:
No Superbugs Just Human Folly
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Acquired Antibiotic Resistance:
No Superbugs Just Human Folly
•We pretty know how & why it happens
•We have a very good idea how to slow it down
•Nationally & Globally we can not organize ourselves to
act
•“Wicked Problem”
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Intermission
• End of Part One
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Part 2
• 1. How bad is the situation now ?
• 2. Is it likely to get better or worse ?
• 3. Does what happens in one species matter
for others (and vice versa)
• 4. What can be done ?
• 5. What is likely to be done ?
28
How Bad is the Situation Now ?
Pretty bad ?
1. Increasing Levels of Resistance
2. Very Few New Antibiotics
(even fewer that matter-Why ?)
29
EARS-NET S. aureus
EARS-NET Enterococcus faecium
EARS-NET E. coli
EARS-NET ESBL E. coli
EARS-NET Klebsiella pneumoniae
EARS-NET ESBL K. pneumoniae
EARS-NET Carbapenem Resistant K. pneumoniae
Spreading Faeces & Eating Faeces
Clonal Spread of Bacteria and a Scattering Gene Cloud
E. coli
K. pneumoniae
Enterocooccus faecium
(Clostridium difficile & Norovirus)
All Enteric Bacteria
37
Global Inequity in a Global Village
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Cancun Airport 2013
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The Global Nature of the Problem
Travel & Trade
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Why So Few New Antibiotics ?
Under investment ?
More public funding for research
More tax breaks for industry
Less rigorous licensing for new antimicrobials
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Why So Few New Antibiotics ?
Less rigorous licensing for new antimicrobials
Current Requirement
“not noticeably worse that some existing
comparator treatment
(not always the best comparator in my view)
42
Why So Few New Antibiotics ?
Conservative Evolution
The Number of Easy Biochemical Targets
Was Probably Quite Limited
BMJ: Cormican and Vellinga
43
Is It Likely to Get Better or Worse ?
The Situation is almost certain to get Worse
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Animals & Humans Links
Overview
• All Use Drives Resistance
• Bacteria transfer between species
• (For Proof See Salmonella & Campylobacter
& VTEC)
• Resistance genes transfer between species
of bacteria
45
Animals & Humans Links
• The Challenges of Linking Animal & Human Data
• What is “Resistant”
• Is resistant for a cow resistant in a chicken or a
person ?
46
A Common Frame For Interpretation ECOF
• Wild Type (Original Shape - Sensitive)
• Non- Wild Type (New Shape - Not really sensitive
even if not outright resistant)
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What Could Be Done ?
• Awareness & Education
• Guidelines
• Whistling in the Wind
• Powerful Social, Professional and Economic
Factors Sustain Current Practice (Wicked)
48
What Could Be Done ?
• Awareness & Education
• Guidelines
• Preparation to Accept Regulation
• Surveillance & Targets
• Incentives & Penalties
49
What Else Could Be Done ?
• Reducing Diagnostic Uncertainty
• Reducing Fear (of complaint & litigation)
• Accepting Death (humans & animals)
50
What is Likely to Be Done – More Hand
Wringing
• Far Too Little & Far Too Late
• The Tragedy of the Commons
• The “Wicked Problem”
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HAND DISINFECTION WITH ALCOHOL BASED
HAND RUB
IS EFFECTIVE FOR MOST BACTERIA
IF YOUR HANDS ARE ALREADY CLEAN
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Acknowledgments
•
Dearbhaile Morris, Niall DeLappe, Catherine Ludden, Akke
Velliinga, Sandra Galvin, Aoife Callanan, Sinead Duane,
Andrew Murphy, Christine Domegan, Eamon O’Shea and
others
• Environmental Protection Agency
• Health Research Board
• & You
53
Jimmy Buffet Connection
• Margaritaville (adapted lyric)
• Some people claim there’s a superbug to
blame
• But I know its our own damn fault
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