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Antimicrobial Resistance (AMR)


DISCLAIMER

• The Content in this presentation is only intended for healthcare professionals in India . The medical

information in this presentation is provided as an information resource only, and is not to be used or relied

on for any diagnostic or treatment purpose. “

• “The views and opinions mentioned in the presentation is strictly that of the author and the individuals

expressing the same and Pfizer may not necessarily endorse the same. Pfizer (including its parent,

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Mumbai 400 051, India

• For the use only of Registered Medical Practitioners or a Hospital or a Laboratory PP-NXM-IND-0239 1st Apr 2019


Learning Objectives

• Risk, Causes and Burden of AMR

• Management of AMR

• Elements of Antimicrobial Stewardship

• Recommendations on Antimicrobial Stewardship

• Avoiding AMR in Medical Practice


Chapters in this Module

• Introduction to Antimicrobial Resistance (AMR)

• Antimicrobial Stewardship

• Antimicrobial Stewardship Strategies

• Avoiding AMR in your practice


Introduction to Antimicrobial Resistance

What is AMR?

• “Loss of effectiveness of any

anti-infective medicine, including

antiviral, antifungal, antibacterial

and anti-parasitic medicines”

(NICE)

NICE. Antimicrobial stewardship: systems and processes for effective antimicrobial medicine use [Internet]. 2018 [Cited 31 March 2019]. Available from: https://www.nice.org.uk/guidance/ng15/chapter/1-Recommendations

Antibiotic

https://www.nice.org.uk/guidance/ng15/chapter/1-Recommendations

Causes of AMR

Over Prescribing

of antibiotics

Patients not taking

antibiotics as prescribed

Unnecessary antibiotics

used in agriculture

Poor infection control in

hospitals and clinics

Poor hygiene and

sanitation practices

Lack of rapid laboratory

tests

CDC Global Health - Infographics - Antibiotic Resistance The Global Threat [Internet]. Cdc.gov. 2018 [Cited 31 March 2019]. Available from: https://www.cdc.gov/globalhealth/infographics/antibiotic-resistance/antibiotic_resistance_global_threat.htm

https://www.cdc.gov/globalhealth/infographics/antibiotic-resistance/antibiotic_resistance_global_threat.htm

Global Antibiotic Consumption (2000 - 2010)

Between 2000 and 2010, consumption of antibiotic drugs has increased by 36%

Increased consumption of carbapenems (45%) and

polymixins (13%)

Brazil, Russia, India, China, and South Africa accounted for 76% of

this increase

Increased cephalosporin and fluoroquinolone consumption, mainly in middle-income countries like India and

China

Van Boeckel TP, et al. Global antibiotic consumption 2000 to 2010: an analysis of national pharmaceutical sales data. Lancet Infect Dis. 2014;14(8):742-50.

No major new classes of antibiotics have been discovered since 1987 and very few antibacterial agents are in development to meet the challenge of multidrug resistance.Silver LL. Challenges of antibacterial discovery. Clin Microbiol Rev. 2011;24(1):71-109.GLOBAL ACTION PLAN ON ANTIMICROBIAL RESISTANCE [Internet]. Wpro.who.int. 2015 [Cited 31 March 2019]. Available from: http://www.wpro.who.int/entity/drug_resistance/resources/global_action_plan_eng.pdf

Antibiotic Pipeline is Drying Up

10

1 1

5

7

23

2

0 0 0

1900s 1910s 1920s 1930s 1940s 1950s 1960s 1970s 1980s 1990s 2000s 2010s

Number of antibiotic classes discovered or patented

http://www.wpro.who.int/entity/drug_resistance/resources/global_action_plan_eng.pdf

Impact of Emerging AMR

Patients infected by drug-resistant bacteria are at increased risk of worse clinical outcomes and death.They also consume more health-care resources

In many countries, resistance in E. coli to fluoroquinolonehas made them ineffective for the treatment of Urinary tract infection

Around, 64% of patients with MRSA are more likely to die than people with a non-resistant form of the infection

Antimicrobial resistance Factsheet [Internet]. World Health Organization. 2018 [Cited 31 March 2019]. Available from: http://www.who.int/mediacentre/factsheets/fs194/en/

Carbapenem resistance in K. pneumoniae is increasing globally. In some countries, carbapenemsdo not work in more than half of people treated for K. pneumoniae infections

http://www.who.int/mediacentre/factsheets/fs194/en/

AMR in Gram Positive Organisms

In the USA, MRSA causes ~19,000 in-hospital deaths/year, comparable to annual deaths caused by AIDS, viral hepatitis and

tuberculosis

In India, MRSA rates are as high as 54.8%

Penicillin-non-susceptible pneumococci (PNSP) are widespread globally (<5% in Northern Europe; >60% in South Africa)

Resistance to macrolides is prevalent in pneumococci (>40–50%) of isolates

Boucher HW, Corey GR. Epidemiology of methicillin-resistant Staphylococcus aureus. Clin Infectious Dis. 2008;46(Supplement_5):S344-9.Laxminarayan R, Chaudhury RR. Antibiotic Resistance in India: Drivers and Opportunities for Action. PLoS Med. 2016;13(3):e1001974.Rossolini GM, et al. Epidemiology and clinical relevance of microbial resistance determinants versus anti-Gram-positive agents. Curr Opin Microbiol. 2010;13(5):582-8.

AMR in Gram Negative Organisms

Cephalosporins resistance in E. coli and K. pneumoniae is highly variable in different

parts of the world

In India, fluoroquinolone resistance among invasive S. Typhi isolates increased from

8% in 2008 to 28% in 2014

P. Aeruginosa:

USA and Europe: 5-10%

Japan: 2.8%

Carbapenem-resistant Acinetobacter:

Europe and Latin America: 30%

USA: 5-10%

Laxminarayan R, Chaudhury RR. Antibiotic Resistance in India: Drivers and Opportunities for Action. PLoS Med. 2016;13(3):e1001974.Burden of Resistance to Multi-Resistant Gram-Negative Bacilli [Internet] MRGN. 2018 [Cited 31 March 2019]. Available from: https://www.reactgroup.org/uploads/publications/react-publications/burden-of-resistance-to-MRGN.pdf.

https://www.reactgroup.org/uploads/publications/react-publications/burden-of-resistance-to-MRGN.pdf

Mechanism of Resistance

Mulvey MR, Simor AE. Antimicrobial resistance in hospitals: how concerned should we be?. Canadian Medical Association Journal. 2009;180(4):408-15.

Nuermberger E, Bishai W. The Clinical Significance of Macrolide‐ResistantStreptococcus pneumoniae:It’s All Relative. Clin Infectious Dis. 2004;38(1):99-103.

Inactivating enzymeβ-lactamsAminoglycosidesMacrolidesRifamycins

Permeability barriersTetracyclinesTrimethoprimSulfonamidesVancomycin

Target ModificationAltered penicillin bindingproteinsAltered DNA gyraseMacrolidesFluoroquinolonesRifamycinsVancomycinPenicillinsAminoglycosides

Did you know?

Efflux mechanism accounts for more that 2/3 of resistant isolates

EffluxMacrolidesFluoroquinolonesAminoglycosidesTetracyclinesβ-lactams

https://thenounproject.com/term/question/727759




Knowledge Check! (Option 2)

• Patient presents a history of persistent cough and sputum since a month. On further questioning, you learn that he has been taking an antibiotic recommended by a local pharmacist every day. How do you proceed next? – Order a sputum culture

– Find the details of the medication– Refer to an infectious diseases specialist– Prescribe a broad spectrum antibiotic– All of the above

That is incorrectExplanation: Persistent cough and other symptoms of infection could be caused by organisms resistant to Antibiotics. In such cases a presumptive diagnosis should be followed with the culture. Patients should be sensitized about inappropriate use of antibiotics.

• Should the patient continue the antibiotic recommended by the local pharmacist?– Yes– No

Explanation: Patients should be educated about the danger of inappropriate use of antibiotics prescribed by unauthorized personnel

Knowledge Check! (Option 2)

• What is the most common mechanism by which micro-organisms develop resistance to antibiotics?

– Modification

– Efflux

– Cell wall changes

– Target modification

– Explanation: The most common mechanism for acquiring AMR is activation of drug efflux pump. Over two-third of all resistant isolates show efflux to be the causative mechanism of resistance.

– Congratulations! You have a clear idea of basics on antimicrobial resistance


Antimicrobial Stewardship


What is Antimicrobial Stewardship?

“An organizational or healthcare-system-wide approach to promoting

and monitoring judicious use of antimicrobials to preserve their future

effectiveness” (NICE)

Antimicrobial stewardship: systems and processes for effective antimicrobial medicine use | Guidance and guidelines | NICE [Internet]. Nice.org.uk. 2018 [Cited 31 March 2019]. Available from: https://www.nice.org.uk/guidance/ng15/chapter/What-is-this-guideline-about-and-who-is-it-for

https://www.nice.org.uk/guidance/ng15/chapter/What-is-this-guideline-about-and-who-is-it-for

Core Elements of Hospital Antibiotic Stewardship Programs

• Leadership Commitment: Dedicating necessary human, financial and information technology resources

• Accountability: Appointing a single leader responsible for program outcomes. Experience with successful programs show that a physician leader is effective

• Drug Expertise: Appointing a single pharmacist leader responsible for working to improve antibiotic use

• Action: Implementing at least one recommended action, such as systemic evaluation of ongoing treatment need after a set period of initial treatment (i.e. “antibiotic time out” after 48 hours)

• Tracking: Monitoring antibiotic prescribing and resistance patterns

• Reporting: Regular reporting information on antibiotic use and resistance to doctors, nurses and relevant staff

• Education: Educating clinicians about resistance and optimal prescribing

Core Elements of Hospital Antibiotic Stewardship Programs | Antibiotic Use | CDC [Internet]. 2018 [Cited 31 March 2019]. Available from: https://www.cdc.gov/antibiotic-use/healthcare/implementation/core-elements.html

https://www.cdc.gov/antibiotic-use/healthcare/implementation/core-elements.html

Stewardship Team

Doron S, Davidson LE. Antimicrobial Stewardship. Mayo Clinic Proc. 2011;86(11):1113-1123.

An Infectious Disease Physician A Pharmacist An Infection Preventionist

Collaborates with

Microbiology Laboratory Hospital Epidemiology Hospital Administration

Steps for Antimicrobial Stewardship

Understand problem pathogens and antimicrobial use at your institution

Assess current resources, including current staff, electronic database, computerized entry systems

Determine priority areas and plan for interventions

Engage hospital leaders and develop a business plan that covers expenditures, personnel costs etc.

Identify what outcome data you need to collect and have a pre-determined timeline for assessment of goals

Doron S, Davidson LE. Antimicrobial Stewardship. Mayo Clinic Proc. 2011;86(11):1113-23.

Aspects of Antimicrobial Stewardship

Doron S, Davidson LE. Antimicrobial Stewardship. Mayo Clinic Proc. 2011;86(11):1113-23. Dellit TH, et al; Infectious Diseases Society of America; Society for Healthcare Epidemiology of America. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis. 2007;44(2):159-77.

Prospective audit of antimicrobial use

Infectious diseases physician or clinical pharmacist

Direct interaction and feedback to the prescriber

Formulary restriction and preauthorization

Restricting use of antibiotics without prior authorization to all except selected trained/qualified clinicians

Post-prescription management

Modification of the initial empiric antimicrobial regimen based on

culture data, other laboratory tests and clinical status of the patient

Aspects of Antimicrobial Stewardship

Dellit TH, et al; Infectious Diseases Society of America; Society for Healthcare Epidemiology of America. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis. 2007;44(2):159-77.

Education

Multidisciplinary guidelines incorporating local microbiology and resistance patterns

Evidence-based practice guidelines

Influence prescribing behavior and provide a foundation of knowledge of stewardship strategies

Knowledge Check 2

• Which of the following are strategies of antimicrobial stewardship?– Prospective audit of antimicrobial use

– Formulary restriction and pre-authorization

– Post-prescription management

– All of the listed options

Explanation: All of the listed options are strategies of antimicrobial stewardship. Individual strategy is used in tandem to create an appropriate, multi-faceted plan of action for antimicrobial stewardship programs.

• In an antimicrobial stewardship program, the sole stakeholder is an infectious disease specialist to avoid multiple overlapping decision loops– True

– False

Explanation: An antimicrobial stewardship program is multidisciplinary, and has multiple stakeholders, including an infectious disease specialist, a pharmacist, a specialist in prevention of infections, liaising with the hospital administration, the epidemiology team and the microbiologist

Knowledge Check 2

• Antimicrobial usage is adjusted and changed in response to culture results to suitably target causative organisms– True

– False

Explanation: Antimicrobial usage should be responsive to local patterns of antimicrobial resistance, and the choice of treatment should be guided by results from microbiological cultures to specific pathogens, and study sensitivity for targeted actions.

• Choose the best option which describes the scope of "formulary restriction" – Prohibits any use of antibiotics

– Restricts only small set of antibiotics

– Leaves the decision about antibiotic use in the hands of all the physician collectively

– Restrict antibiotic use for all but a selected group of doctors

Explanation: Formulary restriction is a strategy that involves regulation of antibiotic usage by strictly limiting the use of antimicrobials in everyday practice to select a set of trained and qualified physicians


Antimicrobial Stewardship Strategies


Antimicrobial Stewardship Goal

• Optimize clinical outcomes and minimize unintended consequences of antimicrobial use

• Example of interpretation for local ASP goals:• Improvement in quality of patient care

• Minimize toxicity from antimicrobial therapy

• Reduce antimicrobial resistance

• Reduce cost of antimicrobial therapy


Antimicrobial Cycling


• Problem:

– Antibiotic use mandated for infectious diseases

• Solution:

– Scheduled protocol for removal and substitution of a specific antimicrobial or antimicrobial class

– Introduce controlled variety in antimicrobial use to minimize selection pressure

Combination Therapy


• Problem:

– Monotherapy may not be sufficient to target highly variable pathogens

• Solution:

– Combination of antibiotics when there is a high organism load combined with a high frequency of mutational resistance (e.g. tuberculosis or HIV)

– Not a routine practice

De-escalation of Therapy


• Problem:– Continuing excessive broad therapy

contributes to selection of antimicrobial resistance pathogens

• Solution:– De-escalation of empirical therapy on the

basis of culture results. Helps to eliminate redundant combination therapies

– Effectively targets the causative pathogen resulting in decreased antimicrobial exposure

– Substantial cost savings

Dose Optimization


• Problem:

– Individuals may have variable response to standard therapy

• Solution:

– Dosing should account for:

• individual patient characteristics,

• causative organism and site of infection

• pharmacokinetic and pharmacodynamic characteristics of the drug

Conversion from Parenteral to Oral Therapy


• Problem:

– Serious infections requiring hospitalization generally initiated with parenteral therapy

• Solution:

– Allow conversion to oral therapy if pre-defined treatment targets are met

– Use antimicrobials with higher oral bioavailability; e.g. fluoroquinolones, oxazolidinones, metronidazole, clindamycin, trimethoprim-sulfamethoxazole, fluconazole, and voriconazole


Avoiding AMR in your Practice

The 4 D’s of Optimal Antimicrobial Therapy

Prescribing the right Drug

Prescribing the right Dose

De-escalate to pathogen directed therapy

Right Duration of therapy

Joseph J, Rodvold KA. The role of carbapenems in the treatment of severe nosocomial respiratory tract infections. Expert Opin Pharmacother. 2008;9(4):561-75.Doron S, Davidson LE. Antimicrobial Stewardship. Mayo Clinic Proc. 2011;86(11):1113-1123.

“The optimal care of an infected patient means treating with the

correct, properly dosed antibiotic and one that has the least likelihood of

causing collateral damage”

Consideration for Prescribing Antibiotics

Prescribe only when there is likely to be a clear clinical benefit

Consider a ‘No’ or ‘Delayed’ antibiotic strategy for acute self-limiting URTI and mild UTI symptoms

Use simple antibiotics if possible, avoid broad spectrum antibiotics

Prescribe the shortest effective course and most appropriate dose

Use appropriate route of administration

Review microbiology results and de-escalate to pathogen directed narrow spectrum treatment where appropriate

General guidelines for antibiotic prescription [Internet]. Health.govmu.org. 2018 [Cited 31 March 2019]. Available from: http://health.govmu.org/English/Documents/General%20guidelines%20for%20antibiotic%20prescription.pdf

http://health.govmu.org/English/Documents/General guidelines for antibiotic prescription.pdf

Advice for your Patients

A Patient's Guide to Proper Antibiotic Usage [Internet]. Pharmacytimes.com. 2018 [Cited 31 March 2019]. Available from: http://www.pharmacytimes.com/publications/issue/2004/2004-12/2004-12-4835

Never let patient insist on prescribing an antibiotic

Good hand-washing techniques

There is no need for antibiotics in viral infections

Never take antibiotics that

were prescribed for someone else

Never take antibiotics that were

left over from a previous infection or

past prescription

Finish the antibiotic course

prescribed even if the patient starts feeling better and

the symptoms subside

http://www.pharmacytimes.com/publications/issue/2004/2004-12/2004-12-4835

Four Core Actions to Fight Resistance

About Antimicrobial Resistance | Antibiotic/Antimicrobial Resistance | CDC [Internet]. Cdc.gov. 2018 [Cited 31 March 2019]. Available from: https://www.cdc.gov/drugresistance/about.html

1

Prevent infections, thereby preventing

the spread of resistance

Gather data on AMR infections, causes of infections and risk

factors to develop strategies to prevent resistant bacteria from

spreading

Improve antibiotic prescribing and

stewardship – stop inappropriate

antibiotic usage

Develop new drugs and

diagnostic tests

2 3 4

https://www.cdc.gov/drugresistance/about.html

Knowledge Check!

• Select the 4Ds of optimal antimicrobial therapy

– Drug, Dose, Delivery and Documentation

– Drug, Dose, De-escalation and Duration

– Documentation, Drug class, Debridement and De-escalation

– Delivery, Dose, Dilution and Drug

Explanation: Prescribing the right antibiotic drug, at the right dose, for the right duration and de-escalating the therapy once the symptoms subside ensures appropriate management of infections