antimicrobial resistance: the global response · 2020. 12. 10. · "superbugs“ bbc news september...

Patrick R. Murray, PhD, F(AAM), F(IDSA)

VP, WW Scientific Affairs

Becton Dickinson Life Sciences

Antimicrobial Resistance:

The Global Response

1

Antimicrobial Resistance

is a Global Problem

Global Prevalence of ESBL CTX-M Strains Doi et al, J Travel Med, 2017

Carbapenem Resistance in Enterobacteriaceae Friedman et al, Infect Control Hosp Epidemiol 2017

Colistin Resistance Sun et al, Trends Microbiol, 2018

Evolution of Antibiotic Resistance

in Gram-Positive Bacteria

Bacteria have shown a remarkable ability to develop

resistance to new antibiotics:

• 1950s – Penicillin was used to treat S. aureus infections;

resistance developed due to penicillinase

• 1970s – Penicillinase-resistant penicillins introduced (e.g.,

methicillin, oxacillin); MRSA strains developed

• 1980s – Vancomycin used to treat MRSA; vancomycin resistance

developed in Enterococcus

• 2000s – Linezolid used to treat MRSA and Enterococcus;

linezolid resistance developed

Evolution of Antibiotic Resistance

in Gram-Negative Bacteria

• 1970s – Ampicillin and 1st generation cephalosporins used to

treat E. coli and Klebsiella; resistance due to TEM and SHV beta-

lactamases

• 1980s and 1990s – 2nd and 3rd generation cephalosporins used

to treat Enterobacteriaceae; resistance to all penicillins and

cephalosporins developed due to extended spectrum beta-

lactamases (ESBLs)

• 1990s and 2000s – ESBL strains treated with carbapenems;

resistance to all beta-lactams developed due to carbapenemases

• Today – Colistin used to treat antibiotic resistant

Enterobacteriaceae, Pseudomonas, and Acinetobacter; colistin

resistance developed

Global Infections with Drug-Resistant Microbes 2017 Organization for Economic Co-operation and Development (OECD) Report

8

Antibiotic Usage by European Country European Centre for Disease Prevention and OECD Health Statistics

9

The 193 countries of the United Nations agreed a landmark

declaration to rid the world of drug-resistant infections or

"superbugs“ BBC News September 21, 2016

Global Pledge to Stamp Out

Drug-resistant Infections

Rio Olympics Pollution

A Global Problem Requiring a Global Solution

10

WHO Global Action Plan on Antimicrobial

Resistance (AMR) – One Health Plan

• Education – educate the medical community and public about

antimicrobial resistance

• Surveillance – monitor AMR globally, regionally, locally

• Infection prevention – prevent transmission from environment,

animals, and patients (asymptomatic and symptomatic)

• Infection control and antibiotic stewardship – optimized use of

antibiotics in human and animal health

• Diagnostics and therapeutics – Increase investments in new

medicines, diagnostics, vaccines, and other interventions; transition

from empiric treatment to directed treatment through the use of

diagnostics

Antibiotic Resistance - Surveillance


• Global surveillance programs

– WHO Collaborating Centre for Surveillance of Antimicrobial Resistance

(WHONET)

– UN Interagency Coordination Group on Antimicrobial Resistance (IACG)

– European Antimicrobial Resistance Surveillance Network (EARS-Net)

– EUCAST reports

– Large research collaboratives

• GLASS – Global Antimicrobial Resistance Surveillance System

• AWARE – Assessing Worldwide Antimicrobial Resistance and Evaluation




(WHONET)



– EUCAST reports




• Regional surveillance programs

– Country-wide programs




(WHONET)



– EUCAST reports




• Regional surveillance programs

– Country-wide programs

• Local surveillance programs

– Hospital antibiograms

– Published community records

Education and Surveillance

• In the last 2 years, I have worked on AMR programs in

countries in Asia including China, Western and Eastern

Europe, the Middle East, and North and South America; all

have initiated educational programs and country-wide

surveillance programs.

• Many of the surveillance programs are not comprehensive

and are not integrated with specific antibiotic stewardship

programs.

• In general, the programs do not have well-defined, realistic

goals for impacting the development and spread of resistant

bacteria and fungi.

• Targeted goals and metrics to assess progress are needed for

all AMR programs.

Infection Prevention and Control


• Goal: Reduce the risk of transmission of pathogens from

both recognized and unrecognized sources




• Unrecognized carriers of resistant organisms are the

most common source of patient-to-patient transmission

in the hospital




• Unrecognized carriers of resistant organisms are the

most common source of patient-to-patient transmission

in the hospital

• Prevention and control requires a comprehensive

program:

– Assess risk of infection

– Establish hospital guideline policies

– Monitor compliance

– Enforce policies

Antimicrobial Stewardship

17

• Antibiotic stewardship in the hospital setting is necessary

to (1) prevent the overuse of antibiotics, (2) inappropriate

treatment of infected patients, and (3) selection of

antibiotic resistant bacteria


17





• Antibiotic resistance is increasing in an era when

alternative drugs are not available and relatively few are

in development


17







in development

• Traditional manual and automated antibiotic

susceptibility tests may be inadequate in detecting all

resistant organisms (e.g., resistance to carbapenems

and colistin)


17







in development

• Traditional manual and automated antibiotic

susceptibility tests may be inadequate in detecting all

resistant organisms (e.g., resistance to carbapenems

and colistin)

• Rapid molecular tests can provide sensitive methods for

detecting colonized patients.


17

Antimicrobial Stewardship Program – collaborative,

coordinated program of intervention designed to improve

antimicrobial prescribing (right drug, dose, duration and

route of administration) to optimize clinical outcomes while

minimizing unintended consequences of antimicrobials

such as toxicity, selection of pathogenic organisms, and

emergence of resistance.

19

Antibiotic Stewardship Guidelines: 2016 A focused Approach

19


• Targeted antibiotics such as those that treat emerging

drug-resistant bacterial infections, should require

preauthorization.

19




preauthorization.

• Syndrome-specific interventions – focused multifaceted

interventions for the treatment of specific syndromes,

rather than trying to improve treatment of all infections.

19




preauthorization.

• Syndrome-specific interventions – focused multifaceted

interventions for the treatment of specific syndromes,

rather than trying to improve treatment of all infections.

• Rapid diagnostic testing – rapid testing of blood cultures or

respiratory cultures can lead to specific, directed therapy.

CDC Guidance on Antimicrobial Stewardship

20


20

1. Leadership commitment – antibiotic stewardship involves many –

physicians, pharmacists, nurses, and administrators


20



2. Accountability – a single leader must be responsible for program

outcomes


20




outcomes

3. Drug expertise – a single pharmacist must be appointed to lead

initiatives to improve antibiotic use among patients


20




outcomes



4. Action – implement at least 1 recommended action with the goal of

improving antimicrobial use


20




outcomes





5. Tracking – monitor antibiotic resistance and antibiotic prescribing

patterns


20




outcomes






patterns

6. Reporting – regular reports of information on antibiotic resistance

and prescribing practices


20




outcomes






patterns

6. Reporting – regular reports of information on antibiotic resistance

and prescribing practices

7. Education – educate physicians about resistance and optimal

prescribing

Diagnostic Test Stewardship

21

• Selection of empiric antimicrobial therapy is associated

with increased costs and poor patient outcomes.


21



• Directed therapy requires guidance with timely, accurate

diagnostic tests.


21




diagnostic tests.

• An accurate test requires collection of the right

specimen, rapid transit to the laboratory, and skilled

processing of the culture or other diagnostic test.


21




diagnostic tests.

• An accurate test requires collection of the right

specimen, rapid transit to the laboratory, and skilled

processing of the culture or other diagnostic test.

• It is important for the laboratory to adopt workflow

practices that ensure accurate diagnostic testing and

timely communication of results


21

• Evaluated 70 clinical trials that assessed mortality in patients receiving antibiotic therapy for sepsis

• 46.5% of the patients received inappropriate therapy and 36% of these patients died

• There was more than a 2-fold increased risk of mortality with inappropriate therapy

22

• Meta-analysis of 60 publications assessing the impact of antibiotic therapy on gram-negative sepsis

• Inappropriate therapy was associated with 3.3-fold increased risk of mortality and higher costs including longer hospitalization and increased antibiotic usage

Barriers Contributing to Under-utilization

of Diagnostic Tests


of Diagnostic Tests

• Lack of timely reporting of diagnostic test results

• Over the counter access to antimicrobials

• Diagnostics not consistently used to modify

empiric therapy

• Labs fail to use best diagnostic practices such

as 2-3 blood culture sets.


of Diagnostic Tests

• Lack of timely reporting of diagnostic test results

• Over the counter access to antimicrobials

• Diagnostics not consistently used to modify

empiric therapy

• Labs fail to use best diagnostic practices such

as 2-3 blood culture sets.

• Value of diagnostics may not be appreciated by

health care systems

– Inadequate laboratory budget

– Difficulty in quantitating patient benefits and

hospital financial savings

– Lack of reimbursement

US National Action Plan

Goal 1. Slow the Emergence and Prevent the Spread of

Resistant Bacteria

Goal 2. Strengthen National One-Health Surveillance Efforts to

Combat Resistance

Goal 3. Advance Development and Use of Rapid and Innovative

Diagnostic Tests

Goal 4. Accelerate Research and Development for New

Antibiotics, Other Therapeutics, and Vaccines

Goal 5. Improve International Collaboration and Capacities for

Antibiotic Resistance Prevention, Surveillance, and Control

Goals of the US National Action Plan

26

Goal 1. Slow the Emergence and Prevent the Spread of

Resistant Bacteria

1. Implement programs that advance antibiotic-resistance

prevention and foster antibiotic stewardship in healthcare

settings and community

2. Eliminate the use of medically important antibiotics for growth

promotion in food-producing animals and provide oversight

for in-feed and in-water uses of antibiotic

3. Identify and implement measures to foster stewardship of

antibiotics in animals

Goals of the National Action Plan

27

• In 2015, 21,000 tons of antibiotics were used in the United

States.

– 17,200 tons (81.7%) were used in animals

– The bulk of antibiotics were put into food and water to

prevent disease and promote growth; only a small

portion was used to treat disease

– Most antibiotics used in animals are purchased over-

the-counter

Antibiotic Use and Resistance

28

• In 2014, USDA issued their action plan to address antimicrobial resistance


29


– Objective 1: Determine and model patterns, purposes, and impacts of antibiotic use in food-producing animals

– Objective 2: Monitor antibiotic drug susceptibilities of selected bacterial organisms in food-producing animals

– Objective 3: Identify feasible management practices, alternatives to antibiotic use, and other mitigations to reduce AMR associated with food-producing animals and their production environments


29


– Objective 1: Determine and model patterns, purposes, and impacts of antibiotic use in food-producing animals

– Objective 2: Monitor antibiotic drug susceptibilities of selected bacterial organisms in food-producing animals

– Objective 3: Identify feasible management practices, alternatives to antibiotic use, and other mitigations to reduce AMR associated with food-producing animals and their production environments

• In 2017, the FDA ban use of antibiotics for growth promotion and placed all other use of antibiotics (disease prevention, disease treatment) under the guidance of a veterinarian.


29

Goal 2. Strengthen National One-Health Surveillance Efforts to

Combat Resistance

1. Create a regional public health laboratory network to strengthen

national capacity to detect resistant strains, and create a specimen

repository

2. Expand public health surveillance and data reporting, and provide

incentives for reporting of antibiotic-resistance and antibiotic use in

all healthcare settings

3. Develop, expand, and maintain capacity in veterinary and food

safety laboratories to conduct antibiotic susceptibility testing and

characterize zoonotic and animal pathogens

4. Enhance monitoring of antibiotic-resistance patterns, as well as

antibiotic sales, usage, and management practices in the

production chain for food animals and retail meat

Goals of the National Action Plan

30

CDC Antibiotic Resistance (AR) Lab Network

31

National targets for 2020:

• Reduce by 50% the incidence of C. difficile infections compared to 2011

• Reduce by 60% carbapenem-resistant Enterobacteriaceae infections during hospitalization

• Reduce by 35% multidrug-resistant Pseudomonas infections compared to 2011

• Reduce by 50% MRSA bloodstream infections compared to 2011

• Reduce by 25% multidrug-resistant nontyphoidal Salmonella infections compared to 2011

• Reduce by 15% multidrug-resistant M. tuberculosis infections

National Action Plan for Combating Antibiotic-Resistant Bacteria

32

Summary

Summary

• Antimicrobial resistance poses a major global healthcare

problem that will impact on the viability of the healthcare system.

Summary



• Each country must develop a National Action Plan consisting of:

– Education

– Surveillance

– Infection prevention and control

– Antibiotic stewardship

– Diagnostic stewardship

Summary




– Education

– Surveillance




• The components of the plan are inter-dependent so they must

be developed in a coordinated way rather than sequential.

Summary




– Education

– Surveillance






• Each component should be focused on specific identified

problems associated with the development and spread of AMR.

Summary




– Education

– Surveillance






• Each component should be focused on specific identified

problems associated with the development and spread of AMR.

• The success of the program should be measured by specific

metrics including patient outcomes and hospital costs.

antimicrobial resistance: the global response · 2020. 12. 10. · "superbugs“ bbc news september...

Documents