Antibiotic Resistance/Paradox

Question 1

Paradox 1 - How have antibiotics led to poorer hygiene?

Answer 1

Ignorance

Question 2

What are the emerging resistance pathogens?

Answer 2

> MRSA - A pandemic
MDR Enterobacteriaceae - Exploding
Carbapenem resistant Enterobacteriaceae (CRE)
VRE - National issues
Acinetobacter baumannii - Challenging
Clostridium difficile - Sleeper awakening

Question 3

Which form of Enterobacteriaceae does not have a reliable treatment?

Answer 3

Carbapenem resistant Enterobacteriacea (CRE)

Question 4

Paradox 2 - Antibiotic resistance why?

Answer 4

> Overuse

> Not finishing prescriptions

Question 5

When was penicillin introduced?

Answer 5

1944

Question 6

When did S aureus first gain resistance to penicillin?

Answer 6

1950s

Question 7

When was Methicillin introduced?

Answer 7

1959

Question 8

When did S aureus first gain resistance to Methicillin?

Answer 8

1961

Question 9

When was the first true outbreak of MRSA? What antimicrobial was overused as a result?

Answer 9

1963, Increased use of gentamicin

Question 10

When did epidemic MRSA strains evolve/spread? What antimicrobial was overused as a result?

Answer 10

1970s, Increased use of glycopeptides

Question 11

When did Vancomycin resistant S aureus emerge? What is the issue with this?

Answer 11

1996 - “Untreatable MRSA”

Question 12

When did Vancomycin resistant S aureus emerge? What is the issue with this?

Answer 12

1996 - “Untreatable MRSA”

Question 13

What has happened over the years in terms of the end result of MRSA/MSSA?

Answer 13

An increase in mortality

Question 14

What is the cause(s) of the increase in prevalence of MRSA?

Answer 14

> Lack of isolation facilities
Poor hygiene, cleaning and disinfection
Antibiotic mis-use
Standard precautions
Bed/staff shortages
Readmission of MRSA carriers from community

Question 15

What is the relationship of MRSA and antibiotic use?

Answer 15

The higher the consumption of Abx the greater the rates of MRSA

Question 16

What did Price and Sleigh show in the 1970s regarding MDR K. aerogens outbreaks?

Answer 16

When antibiotic use was reduced so was Klebsiella aerogenes

Question 17

If someone someone is prescribed cephalosporin for the next 3 month what is the risk of contracting C difficile?

Answer 17

8 times more likely than the rest of the population

Question 18

If someone someone is prescribed ciprofloxacin for the next 3 month what is the risk of contracting C difficile?

Answer 18

30 times more likely than the rest of the population

Question 19

Which antibiotic puts an individual at highest risk of C difficile infection?

Answer 19

Ciprofloxacin - 30 times more likely than the rest of the population

Question 20

When exposed to Quinoles and other antibiotics what leads to an increased pathogenicity of MRSA?

Answer 20

> Biofilm formation
> Small colony variants
> Efflux
> Hypermutation
> Skin/RT colonization  transmissibility 
> Fibrinonectin-binding protein
>Toxin production eg , TSST-1
> SOS response --> horizontal gene transfer
> Phage induction
> Quorum sensing
> agr expression
> Autolysis
> Intracellular persistence

Question 21

When exposed to Quinoles and other antibiotics what leads to an increased pathogenicity of MRSA?

Answer 21

> Biofilm formation
> Small colony variants
> Efflux
> Hypermutation
> Skin/RT colonization  transmissibility 
> Fibrinonectin-binding protein
>Toxin production eg , TSST-1
> SOS response --> horizontal gene transfer
> Phage induction
> Quorum sensing
> agr expression
> Autolysis
> Intracellular persistence

Question 22

What can lead to an increased risk of colonisation?

Answer 22

> Poor infection control
> MRSA colonization pressure
> MRSA in the environment
> Length of stay, medical devices
> Antimicrobial consumption

Question 23

What can lead to an increased risk on infection?

Answer 23

After colonisation:
> Exposure to fluoroquinolones,
ß-lactams - selection, increased adhesion, increased virulence, patient risk factors, etc.

Question 24

Why may new antibiotics not be the answer to fighting infection?

Answer 24

There is a decreased rate in approvals of new antimicrobials every year

Question 25

Which strain of MDR A.baumannii was shown to lead to the French epidemic?

Answer 25

AYE has an 86-kb resistance island, with 45 resistance genes. These are gained through conjugation

Question 26

Paradox 8 - There are many similarities to Global warming

Answer 26

``` > Known issue yet little change > Continued and even increased use of antbiotics > Societal need/benefits > Running out > Use impacts benefits > Need for better use > Need for new sources > Need for alternatives > Need for integration > Need for a global plan ```

Question 27

Paradox 9 - Non human use is the greatest

Answer 27

> 20-50% antibiotic use in humans is not necessary | > 40-80% antibiotic use in animals questionable value

Question 28

For which AMR bacteria causing human infections are animals reservoirs for?

Answer 28

``` > Salmonella > Campylobacter > E. coli > VRE > C difficile > MRSA + S aureus ```

Question 29

How can bacteria gain resistance?

Answer 29

Horizontal gene transfer

Question 30

For which AMR bacteria causing human infections are humans in the community reservoirs for?

Answer 30

``` > Salmonella > Campylobacter > E. coli > VRE > C. difficile > S. pneumoniae > H. influenzae > MRSA + S aureus ```

Question 31

For which AMR bacteria causing human infections are humans in hospitals reservoirs for?

Answer 31

> P. aeuroginosa > A. baumannii > MRSA

Question 32

Which country has the highest issue with ABx use in animals?

Answer 32

China

Question 33

Paradox 10 - The Global village

Answer 33

> People travel more

Question 34

When should Abx be used?

Answer 34

``` > ICU > Preterm babies > Organ transplants > Cancer chemotherapy > Major surgery ```

Question 35

Published estimates - ECDC, Europe, 2009? (Infection, deaths, illness)

Answer 35

> 6 bacterial infections > 25K deaths per year > 430K illness

Question 36

Published estimates - CDC, USA, 2013? (Infection, deaths, illness)

Answer 36

> 16 bacterial infections > 23K deaths per year > 2M illness

Question 37

Published estimates - O'Neill review, Global, 2013? (Infection, deaths, illness)

Answer 37

> 700k deaths per year

Question 38

Prediction of deaths caused by AMR? Impact GDP by 2050?

Answer 38

> 10 million deaths/year | > GDP = Cost the world up to 100 trillion USD

Question 39

How should infection be targeted in the future?

Answer 39

Prevention: > Antibiotic stewardship > Decline Abx use > Antibiotic holidays