Dr.Satheesh THANGARAJ, Ph.D bioMérieux Singapore Pte Ltd

Antibiotic stewardship,

the way forward… !!!

Waiting Room Poster

Occurrence of Resistance

Evolution through natural selection can occur remarkably quickly when selection pressures are

very strong and reproductive rates are very fast

• Genes acquired by transfer of a small DNA molecule (a plasmid or transposon) from one organism to another

• Unstable in the absence of the antibiotic • Horizontal transmission • Vertical transmission (to daughter cells)

Spontaneous Mutations Gene Acquisition

Mechanisms of Resistance Gene Transfer

A.E. Chatworthy et al. (2007) Nature Chem. Biol.

History of Antimicrobials

Bacteria can quickly become

less susceptible (or resistant) to

any drug

Resistant Bugs are Spreading Rapidly

Source: Centers for Disease Control and Protection (CDC)

The Antibiotic Pipeline is Drying Up Antibacterial Agents Approved 1983-2007

Source: B. Spellberg et al., Clin. Infect. Dis. 38: 1279-86

(2004) (modified).

R.P. Wenzel, N. Engl. J. Med. 351: 523-526 (2004).

5,000 - 5,000,000

compounds

500

250

5

1 or 2

new drugs (may or may not be profitable)

isolation &

screening

further

screening

preclinical

studies

clinical

trials

12 – 15 years

$802 M – 1.7 B

Sources: C. O’Driscoll, Horizon Symposia 2004: Charting Chemical Space.

J. Gilbert et al. IN VIVO: The Business & Medicine Report, 21: 73-82 (2003).

J.A. DiMasi et al. J. Health Econ. 835, 1-35 (2003).

Use our resources wisely

9

Use of antibiotics

10

Source: Pew Charitable trust. Article by Tom Philpott

Antimicrobial stewardship

Use of antibiotics

12 Cosby JL et al., The lancet infectious diseases, 2007

Antimicrobial stewardship

Antimicrobial stewardship: is an inter-professional effort, across the continuum of care

involves timely and optimal selection, dose and duration of an antimicrobial

for the best clinical outcome for the treatment or prevention of infection

with minimal toxicity to the patient

and minimal impact on resistance and other ecological adverse events

such as C. difficile”

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Antimicrobial stewardship [AS] is one of the key strategies to

overcome resistance.

It involves the careful and responsible management of

antimicrobial use.

Nathwani et al., 2012

Goals of Antimicrobial stewardship

Goals of Antimicrobial stewardship

Improve infection cure rates

Reduce surgical infection rates

Reduce mortality and morbidity

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Goal 1:

Improve patient outcomes

Goals of Antimicrobial stewardship

Reduce antimicrobial

consumption, without increasing

mortality or infection-related

readmissions e.g. 22%-36%

reduction in antimicrobial use

[Dellit et al., 2007].

Reduce C. difficile colonization or

infection by controlling the use of

“high-risk” antibiotics [Valiquette

et al,. 2007].

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Goal 2:

Improve patient safety

Goals of Antimicrobial stewardship

Restricting relevant agents

can reduce colonization or

infection with Gram-

positive or Gram-negative

resistant bacteria.

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Goal 3:

Reduce Resistance

Adapted from Lafaurie et al., J. Antimicrob. Chemother.

2012;67:1010-5.

Goals of Antimicrobial stewardship

Savings achieved by

reducing antibiotic costs

can be greater than the

cost of the intervention or

program (from $200,000 to

$900,000 depending on

the studies) [Dellit et al.,

2007]. Such cost-

effectiveness data are

sparse but emerging

[Stevenson et al., 2012;

Davey et al., (Cochrane

Database), 2013].

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Goal 4:

Reduce Health care cost

Implementation of Antimicrobial

Stewardship Programs

Implementation of Antimicrobial

Stewardship Programs

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Antimicrobial Stewardship Programs

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www/cdc.gov/getsmart/healthcare/inpatient-stewardship

Antimicrobial Stewardship Programs

EIGHT KEY STEPS for implementing an Antimicrobial

Stewardship Program (ASP)

1.Assess the motivations

2.Ensure accountability and leadership

3.Set up structure and organization

4.Define priorities and how to measure progress and success

5.Identify effective interventions for your setting

6.Identify key measurements for improvement

7.Educate and Train

8.Communicate 22

Identify effective interventions

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When establishing a new stewardship program, it is best to start

with the core strategies and focus on achieving and maintaining

them before adding some of the supplemental strategies

ASP Strategies

Two core ASP strategies “Front–end strategies” where antimicrobials are made available through

an approval process (formulary restrictions and preauthorization).

“Back-end“ strategies” are where antimicrobials are reviewed after

antimicrobial therapy has been initiated (prospective audit with

intervention and feedback)

More labour intensive

Widely practiced

Easily accepted by clinians

Provide more sustained impact

−Chung et al 2013)

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ASP Strategies

ASP Strategies Front–end strategies

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Hospital ASPs should include an Antimicrobial Prescribing Policy

that is regularly reviewed and updated.

Antimicrobial Prescribing Policy

ASP Strategies Back-end strategies

Antimicrobial review methods

Adapted from Johannsson B. et al. Inf. Control. Hosp. Epidemiol. 2011; 32:367-374.

ASP Strategies Back-end strategies

Audit and direct feedback to prescribers The audit and feedback process

can be managed by either the

medical infection specialist or

specialist pharmacist

Appropriate use of guidance,

Indication for antibiotic,

Choice of agent,

Route [IV vs. oral] of

administration of treatment,

Timeliness of treatment,

Likelihood of on-going

infection or not,

Use of investigation,

Interpretation of microbiology

with a view to de-escalation or

stopping therapy,

Duration of therapy.

Adapted from Malcolm W, Nathwani D, et al. Antimicrob. Resist. infect. Control. 2012;2:3.

ASP Strategies Back-end strategies

Use of diagnostic tools

The role of rapid diagnostics and biomarkers in antimicrobial

stewardship is recognized as a key recommendation by the IDSA.

ASP Strategies Back-end strategies

Use of diagnostic tools

Fast, accurate identification and susceptibility testing, will achieve better

clinical outcomes and timely streamlining/de-escalating of empiric broad-

spectrum antibiotics in seriously ill patients.

End Point Reading

Informative Microbiology

culture results Provides Resistant Phenotypes

Eg. ESBL, MBL, ampC, MRSA, etc

MIC results along with PK/PD could help

in reviewing optimal dose

Prognostic value of Serum PCT

Typical course of PCT serum level according to patient’s response to antibiotic treatment (n=109)

F. Stüber, University Bonn, Lecture at ISICEM, Brussels 2001

ASP Strategies Back-end strategies

Use of diagnostic tools

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Meisner. M., 2010

ASP Strategies Back-end strategies

Use of diagnostic tools

Prognostic value of Serum PCT

Surveillance of antimicrobial use and

Resistance

Surveillance of antimicrobial use and resistance is important At hospital, local and national level

Adapt empiric treatment according to local resistance trends

Demonstrate changes in practice over time.

Identify wards with high antimicrobial usage or use of non-

policy antimicrobials and define targeted interventions

required

Measure improvement after implemented interventions 33

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Further reading…

Thank you very much