speaker 2 - prof victor lim vaccines and resistanc

7/29/2019 Speaker 2 - Prof Victor Lim Vaccines and Resistanc

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ROLE OF VACCINES IN

PREVENTION AND CONTROL OF

RESISTANCE

Prof Victor Lim


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Antimicrobial Resistance

Increasing antibiotic resistance

globally

Antibiotic resistance has

adversely affects clinical

outcomes

increases cost of health

care

Now acknowledged to be one of

the most serious threats to public

health

Patient safety issue WHO 3rd Global Patient

Safety Challenge : Tackling

Antimicrobial Resistance


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Drivers of Antimicrobial

Resistance Overuse of antibiotics

Exerts a selection pressure

Favours the proliferation of resistant strains Lack of infection control

Allows the spread of resistant strains


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The Antibiotic Pipeline is drying up

Infections due to multiply resistant organisms are now frequently encountered

The antibiotic pipeline is drying up.

One strategy is to use vaccines to prevent infections caused by resistant

organisms


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Vaccines as a strategy to

contain antibiotic resistance Vaccines

Prevent colonisation by organisms

Prevent infection by organisms

Reduction of colonisation

Reduces exposure of the organisms to antibiotics

and consequently the development of resistance

Prevention of infection

Reduces the necessity to treat with antibiotics and

thereby reduces antibiotic usage

Reduces transmission of organisms in the community


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Vaccines as a strategy to

contain antibiotic resistance Public Health Authorities are increasingly acknowledging

the role of vaccines in the strategy to contain antibiotic

resistance

a wide range of measures is needed toensure that current ly avai lable antib iot ics

remain effect ive for as lon g as possib le, such

as effective vaccines to prevent infections

Council conclusions on innovative incentives for effective

antibiotics. Council of the European Union, 2009


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Case study : Pneumococcal

Vaccine Immunisation with the 7-valent

conjugate pneumoccocal

vaccine (PCV7) shown to

reduce burden of antibiotic

resistance due to strains

covered by the vaccine.

In US rates of resistant invasive

pneumococcal disease

decreased after introduction of

the vaccination programme in2000

Kyaw MH et al. N Engl J Med

2006; 354:1455


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Vaccine

Klugman K. Clin Infect

Dis 2004; 39:649

Vaccination reduces the transmission of resistant

strains and therefore colonisation among the young

children Vaccination associated with reduction in antibiotic use

Benefit extends to non-immunised as shown by lower

carriage rates of resistant strains among non-

immunised family members


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Vaccine

Dagan R. Clin Microbiol

Infect 2009; 15(S3):16

Pneumococcal resistance rates

declined in the period 2001-

2004

However there was a significant

rebound for the period 2004-2007

Due to the emergence of a

resistant clone 19A not covered

by PCV7


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Vaccine

Van Gils EJM et al.

JAMA 2010; 304: 1099

In a Dutch study infants who

received PCV7 were more likely

to acquire nasopharyngealcarriage of serotype 19A

compared to those who were

unvaccinated


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Vaccine

Nzenze et al. South Afr J Epidemiol Infect 2011;26:253

Capsular switch may be induced by vaccination

Emergence of antibiotic resistance in non-PCV7 strains

due to antibiotic pressure

Recent introduction of a 13-valent pneumococcal

conjugate vaccine (PCV13) which includes 19A

However this may result in the emergence of non-

PCV13 strains

Vaccine strategy needs to complemented by goodantibiotic stewardship


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Influenza vaccine and antibiotic

use

Kwong JC et al. Clin Infect Dis 2009; 49:750

Universal influenza

immunization in Ontario was

associated with reduced

influenza-associated antibiotic

prescriptions. Rates of influenza-associated

antibiotic prescriptions

decreased from 17.9 to 6.4 per

1000 people (RR, 0.36; 95%

CI, 0.260.49)


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Enterococcus faecium

Staphylococcus aureus

Klebsiella pneumoniae

Acinetobacter baumanni

Pseudomonas aeruginosa

Enterobacter sp

IDSA Report on Development Pipeline CID 2009;48 : 1-12


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Staphylococcus aureus

Staphylococcal vaccine

An early trial of a conjugated

Staphylococcus aureus vaccine

(StaphVAX) showed some

promise in conferring partial

protection to patients on

hemodialysis Results from a later, larger

Phase III trial were

unfortunately not as

encouraging.

A clinical trial of another

staphylococcal vaccine (V710)

was abandoned in 2011 after itfailed to show any benefit.

Shinefield H et al.. New Engl J Med2002;

346:491-6.


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Pseudomonas aeruginosa is a major cause of HAI Pan resistant strains are not infrequently

encountered

Potential targets for a vaccine

Flagella Pili

Outer membrane proteins

Lipopolysaccharides

Exotoxin A

Proteases

Sharma A et al. Human Vaccin 2011; 7:999


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Numerous attempts to develop a vaccine against Pseudomonas

aeruginosa.

Whole cell vaccines

Live attenuated Salmonella expressing Pseudomonas antigens

Flagella vaccines

Pili vaccines Exotoxin A toxoid

Adenovirus based vaccine

Although many pre-clinical trials have been conducted, there are

very few clinical trials

No Pseudomonas aeruginosa vaccine is currently licensed forclinical use

Sharma A et al. Human Vaccin 2011; 7:999


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Acinetobacter baumanni

Treatment ofAcinetobacter baumanniiinfections has become a seriousclinical challenge due to the emergence of highly resistant strains

Efforts have begun in developing a vaccine

An inactivated whole cell vaccine has been shown to confer protection in a

murine model of disseminated sepsis

McConnell MJ et al. Vaccine 2010; 29:1

An outer membrane complex vaccine protected mice when inoculated with

clinical strains ofAcinetobacter baumannii

McConnell MJ et al. Infect Immun 2011; 79:518

Various other initiatives including passive immunisation, use of other targets

No clinical vaccine trials yet


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K pneumoniae is a

common cause of HAI

and a major resistance

problem ESBL,

NDM-1, KPC

Attractive as a goal for

vaccine development

5 main virulence

factors that can serve

as targets for the

vaccine

Podschun R. Clin Microbiol Rev 1998; 11:589


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Effort have largely concentrated on 2 surface components Lipopolysaccharide

Capsular polysaccharide

Passive immunisation

antibodies to K antigens capsular polysaccharide

Antibodies to O antigens (lipopolysaccharide) Active immunisation

Whole cell

Bacterial lysate

Protein based (fimbria, outer membrane proteins)

Lipopolysaccharide

Conjugate polysaccharide

None in any advanced stage of clinical trials

Ahmad TA et al. Vaccine 2012;30:2411


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Enterococcus

Vancomycin resistant enterococci (VRE) continues to bea major cause of HAI

Incidence of VRE infections increasing in Asia

Potential targets for vaccines in Enterococcus

Capsular polysaccharide antigens Surface proteins

Not much development in enterococcal vaccines


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Clostridium difficile

Clostridium difficile infection (CDI) is becoming an importantcause of morbidity and mortality in health care facilities

Nearly 95% of CDI cases are healthcare associated; majority

in nursing homes

Kyne L et al. N Engl J Med. 2000:342;390.


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Vaccines to prevent CDI

Gerding DN, Discovery Medicine 2012; 13:75-83,


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CDI Vaccines under development

Gerding DN. Available at www.nfid.org/gm-

node/2548.aspx. Accessed on 2 Oct 2012
http://www.nfid.org/gm-node/2548.aspxhttp://www.nfid.org/gm-node/2548.aspxhttp://www.nfid.org/gm-node/2548.aspxhttp://www.nfid.org/gm-node/2548.aspxhttp://www.nfid.org/gm-node/2548.aspx


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Conclusions

Increasing antibiotic resistance and the lack of new agents in the

antibiotic pipeline makes vaccination an attractive strategy to

meet this challenge

Vaccines can help meet the challenge of antibiotic resistance by

Preventing colonisation and infection by resistant bacteria

Treating resistant infections as adjuncts to antibiotics Limit the transmission and spread of resistant bacteria

Decrease the use of antibiotics

Many initiatives in the development of vaccines to prevent

infections caused by resistant organisms

Still in the early stages of such development

Currently still no vaccine licensed for use to prevent resistantHAIs

speaker 2 - prof victor lim vaccines and resistanc

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