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For Education Purpose Only
Antimicrobial Resistance (AMR)
For Education Purpose Only
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,
subsidiary and affiliate entities) makes no representation or warranties of any kind, expressed or implied;
as to the content used in the presentation and/or the accuracy, completeness of its content.”
• Pfizer Limited, The Capital- A Wing, 1802, 18th Floor, Plot No. C-70, G Block, Bandra - Kurla Complex, Bandra (East),
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
For Education Purpose Only
Learning Objectives
• Risk, Causes and Burden of AMR
• Management of AMR
• Elements of Antimicrobial Stewardship
• Recommendations on Antimicrobial Stewardship
• Avoiding AMR in Medical Practice
For Education Purpose Only
Chapters in this Module
• Introduction to Antimicrobial Resistance (AMR)
• Antimicrobial Stewardship
• Antimicrobial Stewardship Strategies
• Avoiding AMR in your practice
For Education Purpose Only
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
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
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
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
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.
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
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
For Education Purpose Only
Antimicrobial Stewardship
For Education Purpose Only
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
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
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
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Antimicrobial Stewardship Strategies
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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
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.
Antimicrobial Cycling
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.
• 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
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.
• 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
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.
• 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
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.
• 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
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.
• 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
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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
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
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
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
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