mr ben harris - gp cme south/sat_room11_0930_harrisben... · 2016. 8. 13. · important dates years...
TRANSCRIPT
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Mr Ben HarrisMedical Laboratory Scientist
Honorary Lecturer, University of Otago
9:30 - 10:00 Antibiotic Resistance
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Antibiotic ResistanceMutations or Creations?
Ben Harris Med Lab Scientist Infection Prevention & Control
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Important Dates
Years Ago
• 4.5 Billion Origin of the Earth
• 3.5 Billion Prokaryote Bacteria
• 2.5 Billion Oxygen in Atmosphere
• 1.5 Billion Eukaryote cells with nucleus
(animal, plant cell precursors)
• 0.5 Billion Cambrian explosion multicelleular Eukaryote organisms, plants & animals
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Human Infections (1)
Used to be mainly epidemics:
Smallpox, plague, cholera, diphtheria, TB, syphilis, influenza, measles, etc
i.e. exogenous source
Public Health, Sanitation, Vaccinations have largely contained or eliminated these
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Human Infections (2)
Now mainly
Emerge from our own microbiomei.e. endogenous source
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Sharing my microbiome
This vast microbiome is
routinely shared with others
+ animals and environment
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Our Microbial Garden
Emerging realisation of importance of resident microbes to our health and well-being
especially roles played in:
- our immune system
- contributing to food digestion
- acting as first line of defense against pathogens
Many diseases are the result
of disturbed microbiomes
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Global Reality Trend
Global travel people, food, animals, insects
promotes rapid spread
pathogenic bacteria & viruses
+ our shared microbiome
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World Infection Trends (1)“All Microbes are Bad”
‘Old’ diseases return or increase
from endemic areas
e.g. malaria, measles, dengue, foodborne illnesses
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World Infection Trends (2)“All Microbes are Bad”
‘New’ diseases keep emerging
e.g. HIV/AIDS, SARS,MERS, Ebola, Zika
H5N1 (bird flu), H7, H9
2009 H1N1 (swine)
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World Infection Trends (3)Antibiotic Use Creates These:New forms of old diseases - endogenous
MDRO’s including MRSA
ESBL
VRE
C. difficile
CRE carbapenemases
From our own shared microbiome
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World Infection TrendsSummary
Today’s emerging infectious diseases become
tomorrows endemics
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“…. the microbes are educated to resist penicillin … the thoughtless person playing with penicillin is morally responsible for the death of the man who finally succumbs to infection with the penicillin-resistant organism
I hope this evil can be averted ”-Sir Alexander Fleming, June 1945
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Antibiotic Resistance Sharing
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Aust & NZ
Non Human Antibiotic Use
Aust
• 500 tons for animal
production (in1999)
• 300 tons human
therapeutic
+ Horticulture
+ Aquaculture
NZ
• 56 tons for animal
production (in 2009)
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Emerging Antibiotic ResistanceWorldwide Antibiotic Usage
20%
Human
80%
Agriculture
Horticulture
Aquaculture
100% Tx
80%
Community
20%
Hospital
20% Tx80%Increase growth
(i.e. profit)
Prophylaxis
‘Then we eat the
resistance genes’
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300 antibiotic free chickens in 6 cages
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Changes in Intestinal Flora of Farm Personnel after Introduction of a
Tetracycline Supplemented Feed on a Farm
Barn
Stuart B. Levy, M.D., George B. FitzGerald, Ph.D., and Ann B. Macone, B.S.
N Engl J Med 1976; 295:583-588
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Barn Chickens Fed Tetracycline
• 300 antibiotic free chickens in cages
• Tetracycline feed additive in 2 cages at
one end of barn only
• Farming family of 11 (2 adults + 9)
• Gut flora: E. coli, P. mirabilis, enterococci
+ Kleb. pneumoniae, Ps. aeruginosa, Acinetobacter
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Chickens Fed Tetracycline
Within one week most chicken intestinal
flora resistant to tetracycline
(E coli, Pr mirabilis, enterococci)
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Chickens Fed Tetracycline (contd)
After Tetra use for ≥ 10 weeks in chickens
> 50% E coli also resistant to
• Streptomycin
• Ampicillin
• Carbenicillin
• Sulphonamides
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Chickens Fed Tetracycline
Farm workers then developed increased
intestinal resistance
Within six months 31.3 % weekly faecal
samples from farm dwellers had
>80% tetracycline resistant bacteria
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Key Point
Ongoing use of a single antibiotic
selects resistance for
multiple structurally unrelated ABs
via linkage genes, plasmids, transposons
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Antibiotic Dispersion Effect in Populations of People or Animals
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Antibiotic Dispersion Effect in Populations of People or Animals
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Nature 25 August 2011 vol 76, p393
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Increasing Frequency of Resistance
MRSA = methicillin-resistant Staphylococcus aureus; VRE = Vancomycin-resistant enteroccoci
FQRP = Fluoroquinolone-resistant Pseudomonas aeruginosa
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E. coli in Midstream Urine
Ampicillin - resistant
Augmentin - resistant
Cefotaxime - intermediate
Ciprofloxacin - resistant
Gentamicin - resistant
Co-Trimoxazole - resistant
Cephalothin - resistant
Chloramphenicol - resistant
Nitrofurantoin - intermediate
Tetracycline - resistant
Imipenem - sensitive BUT how much longer ?
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Post Antibiotic Signs - CRE
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Swiss Travellers StudyKuenzli et al. BMC Infectious Diseases 2014, 14:528
http://www.biomedcentral.com/1471-2334/14/528
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500 People with skin infection
endogenous, from themselves
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5% of 500 Staph aureus infection
MRSA positive, which ones ???
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5% MRSA + and 5% ESBL +
of 500 People
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3 of this 500 have swab takenshould the MRSA be isolated?
Benefits vs Risks of isolating??
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MDRO ApproachSilo or Horizontal Required ?
Staph. aureus E. coli Klebsiella Enterococcus
Subset
MRSA
Subset
ESBL,
Carba
Subset
VRE
Subset
ESBL,
Carba
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Chlorhexidine Exposure Selects
Antibiotic Resistance (MIC’s)Journal of Antimicrobial Chemotherapy (2008) 61, 524– 532
:
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Chlorhexidine Exposure Selects
Antibiotic Resistance (MIC’s)Journal of Antimicrobial Chemotherapy (2008) 61, 524– 532 :
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Antibiotic usage/resistance correlation
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New Antibiotics each 5 years
1983-2011
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Lifespan of Each Antibiotic
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Seeing the Future
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Tragedy of the Commons
Refers to depletion and collapse of a common but limited resource when individuals act selfishly to
maximise personal gains.
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Atlantic Cod Stock Collapse
‘Get it While You Can’
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NZ Antibiotic Use 2012
Assoc Prof Mark Thomas, University of Auckland
Annually:
• 180 AB courses per 100 children <5y
• 60 AB courses per 100 25-29yrs old
the lowest prescribing rate age group! !
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IBD & Number Antibiotic courses
in children correlation
Gut 60, 49-54 :2011 A Hviid et al
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NZ non medical AB use
2009-2011
Horticulture/Agriculture use 19%
From 70,343 kg
to 57,043 kg !
But macrolides
aminoglycosides
cephalosporins including 3rd generation cephalosporins 26%
Sub therapeutic use to be phased out by 2030 !
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Simply• Bacteria do not become resistant
we selectively breed resistance
with every antimicrobial use
• Then we share our large bacterial microbiome mainly by our
hands, coughing & environment
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Summary
A Hospital or LTCF resistant bug is one
which we HCW’s gave them
An MDRO carrier is not the problem but a
symptom of a much larger issue
We are rapidly squandering our
limited antibiotic resource
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Bug Sharing
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Our Actions Now Are Our Future
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Simply
• Bacteria do not become resistant
we selectively breed resistant strains
• Then we share our large bacterial microbiome mainly by our
hands, coughing & environment
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Unique, Only Antibiotics• use of AB in one patient can compromise
efficacy in another
• lose efficacy over time & must be continually
replaced
• need to be used sparingly to prolong their
efficacy
• for which we actively discourage use when
newly approved BUT R&D/profit implications
Todays choices affect future patient
outcomes
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Antibiotic Summary
• Resistance emerging, increasing, evolving
• Few new antibiotics in pipeline
• Geographic variations in resistance patterns
use & adapt to these
• Many challenges to stop transmission
& greatly reduce AB use
• Novel treatment approaches needed
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Summary• Every Antibiotic Use helps select for
microbial resistance
• HCW’s (hands) are the most common
vector for spreading MDRO’s to patients
• A Hospital or LTCF resistant bug is one
which we HCW’s gave them
• An MDRO carrier is not the problem but a
symptom of a much larger issue
We are increasingly rapidly squandering our
limited antibiotic resource
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Toronto Jan 2011-March 2012
Ref: International Journal of Infectious Diseases 14S4 (2010) S3–S5
Environmental Cleaning & Horizontal MDRO Awareness
X7 patients in tertiary care Toronto teaching hospital with
New Delhi Metallo beta lactamase-1-producing Kleb pneumonia(NDM1-Kp)
acquired from x2 index patients
Acquisition risk factors:
• Index cases previously hospitalised in endemic area
of India
• 4 of 7 were room mates of affected patients
• 2 of 7 were on the same ward
• 1 was admitted to the room of a discharged infected
patient
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NZ Hand Hygiene Compliance Rates
80% average
X20 DHBs
1 April – 30 June 2015
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NZ DHB Hand Hygiene
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Compliance by HCW category
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How Many HAI’s?
• 1.7 million healthcare infections and 99,000 deaths in the USA annually
• NZ equivalent HAI’s 24,000 infections 1,400 deaths??
• This is 4.5 infections for every 100 hospital admissions
CDC estimates effective infection control could prevent up to 70% of infections
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Hospital Acquired Infection Cost Data
Pennsylvania Health Care Cost Containment Study January 2009
Mortality % Av. Days Stay Av. Cost ($US)
Patients with
HAI
12.2% 19.7 $191,872
Without HAI 2.0% 4.4 $35,168 (5.5x)
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Evolution Adaptation Time
Humans
• In 100,000 years humans
3,000 generations
(assuming 30 years per
generation)
• X10 is one million years
human evolution
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Evolution Adaptation Time
Humans
• In 100,000 years humans
3,000 generations
(assuming 30 years per
generation)
• X10 is one million years
evolution
Bacteria
• Bacteria have 3,000
generations in 1.5 days!
• X10 is 15 days for
equivalent one million
human years evolution but
• also vastly more bacteria to
mutate/evolve/AB selected
• Plus swap genetic material
when alive (species, genera)