-
7/29/2019 Speaker 2 - Prof Victor Lim Vaccines and Resistanc
1/24
ROLE OF VACCINES IN
PREVENTION AND CONTROL OF
RESISTANCE
Prof Victor Lim
-
7/29/2019 Speaker 2 - Prof Victor Lim Vaccines and Resistanc
2/24
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
-
7/29/2019 Speaker 2 - Prof Victor Lim Vaccines and Resistanc
3/24
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
-
7/29/2019 Speaker 2 - Prof Victor Lim Vaccines and Resistanc
4/24
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
-
7/29/2019 Speaker 2 - Prof Victor Lim Vaccines and Resistanc
5/24
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
-
7/29/2019 Speaker 2 - Prof Victor Lim Vaccines and Resistanc
6/24
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
-
7/29/2019 Speaker 2 - Prof Victor Lim Vaccines and Resistanc
7/24
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
-
7/29/2019 Speaker 2 - Prof Victor Lim Vaccines and Resistanc
8/24
Case study : Pneumococcal
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
-
7/29/2019 Speaker 2 - Prof Victor Lim Vaccines and Resistanc
9/24
Case study : Pneumococcal
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
-
7/29/2019 Speaker 2 - Prof Victor Lim Vaccines and Resistanc
10/24
Case study : Pneumococcal
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
-
7/29/2019 Speaker 2 - Prof Victor Lim Vaccines and Resistanc
11/24
Case study : Pneumococcal
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
-
7/29/2019 Speaker 2 - Prof Victor Lim Vaccines and Resistanc
12/24
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)
-
7/29/2019 Speaker 2 - Prof Victor Lim Vaccines and Resistanc
13/24
Enterococcus faecium
Staphylococcus aureus
Klebsiella pneumoniae
Acinetobacter baumanni
Pseudomonas aeruginosa
Enterobacter sp
IDSA Report on Development Pipeline CID 2009;48 : 1-12
-
7/29/2019 Speaker 2 - Prof Victor Lim Vaccines and Resistanc
14/24
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.
-
7/29/2019 Speaker 2 - Prof Victor Lim Vaccines and Resistanc
15/24
Pseudomonas aeruginosa
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
-
7/29/2019 Speaker 2 - Prof Victor Lim Vaccines and Resistanc
16/24
Pseudomonas aeruginosa
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
-
7/29/2019 Speaker 2 - Prof Victor Lim Vaccines and Resistanc
17/24
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
-
7/29/2019 Speaker 2 - Prof Victor Lim Vaccines and Resistanc
18/24
Klebsiella pneumoniae
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
-
7/29/2019 Speaker 2 - Prof Victor Lim Vaccines and Resistanc
19/24
Klebsiella pneumoniae
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
-
7/29/2019 Speaker 2 - Prof Victor Lim Vaccines and Resistanc
20/24
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
-
7/29/2019 Speaker 2 - Prof Victor Lim Vaccines and Resistanc
21/24
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.
-
7/29/2019 Speaker 2 - Prof Victor Lim Vaccines and Resistanc
22/24
Vaccines to prevent CDI
Gerding DN, Discovery Medicine 2012; 13:75-83,
-
7/29/2019 Speaker 2 - Prof Victor Lim Vaccines and Resistanc
23/24
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 -
7/29/2019 Speaker 2 - Prof Victor Lim Vaccines and Resistanc
24/24
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