Biologic therapy ice breaking in rheumatology, Case based approach with appli...
5) anti microbial resistance
1. Recent advance on combating
Anti microbial resistance
Presenter: Dipsikha
Aryal
MPH 2021
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2. Table of Contents
Antimicrobial drugs
Drug resistance
Evolution of antibiotics
Global and National scenario
Present situation
Recent Advance on combatting AMR
Role of vaccine
Policy
Conclusion
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3. Antimicrobial Drugs
General consideration
Antimicrobial drugs are the greatest contribution of the 20th century to therapeutics. Their
advent changed the outlook of the physician about the power drugs can have on diseases.
Antibiotics: These are substances produced by microorganisms, which selectively suppress
the growth of or kill other microorganisms at very low concentrations.
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AM
Ref: KD tripathi; essential of medical pharmacology 8th edition 3
4. Classification of Antimicrobial drugs
Types of organisms against which primarily active
1)Antibacterial: Penicillins, Aminoglycosides, Erythromycin, Fluroquinolones etc.
2)Antifungal: Griseofulvin, Amphotericin B, Ketoconazole etc.
3)Antiviral: Acyclovir, Zidovudine etc.
4)Antiprotozoal: Chloroquine, Pyrimethamine, Metronidazole etc.
5)Anthelmintic: Mebendazole, Pyrantel, Diethyl carbamazine etc.
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5. Drug resistance
It refers to unresponsiveness of a microorganism to an Antimicrobial Agent (AMA) and is akin to
the phenomenon of tolerance seen in higher organisms.
Resistance could be:
Natural resistance: Some microbes have always been resistant to certain AMAs. They lack the
metabolic process or the target site which is affected by the particular drug.
Acquired resistance: This refers to development of resistance by an organism (which was
sensitive before) due to the use of an AMA over a period of time. However, development of
resistance is dependent on the microorganism as well as on the drugs.
3/20/2022 10:44 AM Ref: KD tripathi; essential of medical pharmacology 8th edition 5
6. Drug resistance…contd
Resistance may be developed by mutation or gene transfer:
Mutation: It is a stable and heritable genetic change that occurs spontaneously and
randomly among microorganisms.
Gene transfer (infectious resistance): The resistance causing gene is passed from one
organism to the other; is horizontal transfer of resistance. Rapid spread of resistance can
occur by this mechanism and high level resistance to several antibiotics (multidrug
resistance) can be acquired concurrently.
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7. Antimicrobial Resistance
Antimicrobial Resistance (AMR) occurs when bacteria, viruses, fungi and parasites
change over time and no longer respond to medicines making infections harder to treat
and increasing the risk of disease spread, severe illness and death.
As a result of drug resistance, antibiotics and other antimicrobial medicines become
ineffective and infections become increasingly difficult or impossible to treat.
Superbugs are bacteria or fungi that have developed the ability to withstand
commonly prescribed drugs.
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Ref: https://www.Who.Int/news-room/fact-sheets/detail/antimicrobial-resistance
10. Evolution of Antibiotics and Resistance
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Ref: tackling antibiotic resistance with compounds of natural origin: A comprehensive review
11. Global scenario
As of 29 April, 2019: Currently, at least 700,000 people die each year due to drug-resistant
diseases, including 230,000 people who die from multidrug-resistant tuberculosis.
If no action is taken - warns the UN Ad hoc Interagency Coordinating Group on Antimicrobial
Resistance who released the report – drug-resistant diseases could cause 10 million deaths
each year by 2050 and damage to the economy as catastrophic as the 2008-2009 global financial
crisis. By 2030, antimicrobial resistance could force up to 24 million people into extreme
poverty.
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Ref: https://www.Who.Int/news/item/29-04-2019-new-report-calls-for-urgent-action-to-avert-antimicrobial-resistance-crisis
13. Scenario of Nepal
Studies of antibiotic prescribing pattern in Nepal showed most patients were
unnecessarily prescribed more than one antibiotic concurrently without bacterial
confirmation or susceptibility testing.
A reported 10–42% of patients were prescribed antibiotic for both therapeutic
and prophylactic purposes.
One study conducted in 1998 showed that 68% of drugs prescribed and 70% of
prescriptions for respiratory infections were antimicrobials.
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Ref: https://www.Frontiersin.Org/articles/10.3389/fmed.2019.00105/full
16. Drug resistance in bacteria
For common bacterial infections, including urinary tract infections, sepsis,
sexually transmitted infections, and some forms of diarrhoea, high rates of
resistance against antibiotics frequently used to treat these infections have been
observed world-wide, indicating that we are running out of effective antibiotics.
Resistance to fluoroquinolone antibiotics in E. coli, used for the treatment of urinary
tract infections, is widespread.
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Ref: WHO, 17 November 2021
17. Drug resistance in mycobacterium tuberculosis
Antibiotic resistant Mycobacterium tuberculosis strains are threatening progress in
containing the global tuberculosis epidemic.
WHO estimates that, in 2018, there were about half a million new cases of rifampicin-
resistant TB (RR-TB) identified globally, of which the vast majority have multi-drug
resistant TB (MDR-TB), a form of tuberculosis that is resistant to the two most powerful
anti-TB drugs.
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Ref: WHO, 17 November 2021
18. Drug resistance in viruses
Antiviral drug resistance is an increasing concern in immunocompromised patient
populations, where ongoing viral replication and prolonged drug exposure lead to the
selection of resistant strains. Resistance has developed to most antivirals
including antiretroviral (ARV) drugs.
All antiretroviral (ARV) drugs, including newer classes, are at risk of becoming partly
or fully inactive because of the emergence of drug-resistant HIV (HIVDR).
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Ref: WHO, 17 November 2021
19. Drug resistance in malaria parasites
The emergence of drug-resistant parasites poses one of the greatest threats to malaria
control and results in increased malaria morbidity and mortality.
Artemisinin-based combination therapies (ACTs) are the recommended first-line
treatment for uncomplicated P. falciparum malaria and are used by most malaria endemic
countries.
In the WHO Western Pacific Region and in the WHO South-East Asia Region, partial
resistance to artemisinin and resistance to a number of the ACT partner drugs has been
confirmed.
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20. Drug resistance in fungi
The prevalence of drug-resistant fungal infections is increasing and exasperating the
already difficult treatment situation. Many fungal infections have existing treatability
issues such as toxicity especially for patients with other underlying infections (e.g. HIV).
Drug-resistant Candida auris, one of the most common invasive fungal infections, is
already widespread with increasing resistance reported to fluconazole, amphotericin B
and voriconazole as well as emerging caspofungin resistance.
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21. Drug resistance in Helminthic
For decades anthelmintics have been used as the primary control measure for
worm infections in livestock. However, there has been continuous development
of anthelmintic resistance (AR) by the parasitic worms infecting livestock.
The results of many scientific studies indicate, to variable extents, an increase
of helminth resistance against the well-known groups of anthelmintic which are
benzimidazoles, tetrahydro pyrimidines and macrocyclic lactones.
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Ref: https://www.Dovepress.Com/anthelmintic-resistance-and-its-mechanism-a-review-peer-reviewed-fulltext-article-
idr
23. Advances
Role of Microbiota
Role of vaccine
Bioconjugation
Quorum sensing
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24. Role of Microbiota
The human microbiota has a major impact on the health of the host and it’s
immune response.
Antibiotics not only target pathogens but can also eliminate the commensal
bacterial community, which may provide an opportunity for opportunistic
bacteria to colonize the human host and cause infections.
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25. Microbiota…contd
A principle function of microbiota is to protect the intestine against
colonization by exogenous pathogens and potentially harmful indigenous
micro organisms via several mechanisms which include direct competition for
limited nutrients and the modulation of the host immune response.
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26. 3/20/2022 10:44 AM 26
The intestinal commensal microbiota provides a extreme benefits to the healthy host,
including colonization resistance against pathogens.
Dysbiosis may adversely affect the health status of an individual and prevent protection
against colonization.
Perspective: Antimicrobials alter the structure of the microbiota, expand the host-specific
pool of antimicrobial-resistance genes and organisms, degrade the protective effects of the
microbiota against invasion by pathogens, and may impair vaccine efficacy. Through these
effects on the microbiome they may affect immune responses.
Solutions: The screening of MDR carriage, in particularly in patients admitted to critical care
units.
28. 28
Ref: Rosini R, nicchi S, pizza M and rappuoli R (2020) vaccines against antimicrobial resistance. Front. Immunol. 11:1048. Doi:
10.3389/fimmu.2020.01048
29. 29
Antimicrobial resistance arises when microbial agents such as bacteria, viruses, fungi, and
parasites alter their behaviour to make current conventional medicines inefficient.
Vaccination is one of the most effective strategies to fight antimicrobial resistance.
Vaccines, unlike drugs, are less likely to produce resistance since they are precise to their
target illnesses. Vaccines against infectious agents such as Streptococcus pneumoniae and
Haemophilus influenzae have already been shown to reduce tolerance to antimicrobial
medications; however, vaccines against some antimicrobial-resistant pathogens such as Vibrio
cholerae, Salmonella typhi, Escherichia coli, nosocomial infections require more research and
development.
30. 30
Ref: rosini R, nicchi S, pizza M and rappuoli R (2020) vaccines against antimicrobial resistance. Front. Immunol. 11:1048. Doi: 10.3389/fimmu.2020.01048
Reverse vaccinology enables the selection of potential vaccine
candidates on the basis of the genomic information of a bacterial
strain. The complete genome of a bacterium represents the
catalogues of genes that encode potential antigens that can be
selected, screened and tested as vaccine candidates in both in vitro
and in vivo preclinical model.
GMMA are outer membrane vesicles generated from gram
negative bacteria strains that have been genetically modified to
enhance release of outer membrane vesicles. This aim at
disrupting the outer membrane to the peptidoglycan.
31. 31
Ref: hoelzer et al. Vet res (2018) 49:64
It was demonstrated that use of vaccines in food producing animals substantially
decrease antibiotics use and reduced the risk of the emergence of antibiotic
resistance. This might also have implications for human health as resistance
determinants might be transferred to bacteria that infect humans directly.
Introduction and widespread routine use of a vaccine against Aeromonas salmonicida
led to a significant decrease in antibiotic use in the farmed salmon industry.
Vaccine are promising alternatives that can reduce the need to use antibiotics in food-
producing animals and their direct mitigating impact on antibiotic consumption.
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Nine in every ten large broiler poultry farms in the Kathmandu valley used
antibiotics (for prophylaxis or treatment) and this included six classes and seven
antibiotic types. Three of the antibiotic classes (quinolones, macrolides, and
polymyxins) are considered “highest priority critically important antimicrobials”
for use in humans and this has direct implications on public health.
Six (22%) farms used antibiotics as prophylaxis, while 21 (78%) used it for
therapeutics.
The most commonly used antibiotics were tylosin (47%), colistin (47%), and dual
therapies with neomycin and doxycycline (33%).
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Conjugation is a common mechanism of horizontal gene transfer in bacteria that is
instrumental in the spread of antibiotic resistance among bacteria. Resistance to antibiotics can
arise through mutations in existing genes or through horizontally acquired plasmids or other
mobile genetic elements that encode ABR genes and are abundant in the natural or clinical
environment.
The main aim is to stop the process of conjugation or break the conjugation tube. Tube
breaking process has been successful in lab experiment, however yet to be done in human.
37. Quorum Sensing
Quorum sensing (QS) is a cell–cell communication system that is used in microbial
communities to monitor their population density and adapt to external environment.
Quorum sensing (QS) is a communication mechanism between bacteria that allows
specific processes to be controlled, such as biofilm formation, virulence factor
expression, production of secondary metabolites and stress adaptation mechanisms such
as bacterial competition systems including secretion systems (SS).
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38. 3/20/2022 10:44 AM 38
Bacteria utilize Acylated homoserine lactone (AHL) in communication system
AHL degrade the communication molecules
Breaking communication channel Gene will not work and less
production of virulence factors
40. National Health Policy 2076
6.24 Highlights:
Antimicrobial resistance shall be reduced, one-door health policy shall be
developed and expanded for the control and management of communicable
diseases, environmental pollution such as air pollution, sound pollution and water
pollution shall be scientifically regulated and controlled.
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41. National antimicrobial resistance containment
action plan Nepal 2016
The first section explains what antimicrobial resistance is, how it is spread and
why it is a problem.
Section two outlines the strategic areas of focus for the Government of Nepal
and associated priority actions.
The third section describes the roles and responsibilities of different agencies
involved.
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42. Prevention (1)
I) Individuals
- Only use antibiotics when prescribed by certified health professionals
- Never share left over antibiotics
- Regular handwashing, Preparing food hygienically, avoiding close contact with sick
person
- Follow WHO key to safer food ( keep clean, separate raw and cooked, cook
thoroughly, keep food at safe temperature, use safe water and raw materials).
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43. Prevention (2)
II) Policy makers
- Ensure a robust national action plan to tackle AMR
- Improve surveillance
- Regulate and promote the appropriate use and disposal of quality medicines
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44. Prevention (3)
III) Health Professionals
Prevent infection by ensuring your hands, instrument and environment clean
Report antibiotic resistance infection to surveillance team
Counsel patient to take antibiotics correctly also explain about it’s danger if
misuse
Vaccination
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45. Prevention (4)
IV) Health care industry
Invest in research and development of new antibiotic vaccines and diagnostic
tools.
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46. Prevention (5)
V) Agricultural sector
Give antibiotics to animal under veterinary supervision
Not use antibiotics for growth production or to prevent disease in healthy animal
Vaccinate animals to reduce the need for antibiotics
Promote and apply good practices at all steps of production and processing of foods
from animal and plant sources
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47. Conclusion (1)
Government of Nepal has to strictly implement a national action plan on AMR.
This should include strategies and policies to promote good husbandry
practices, nationwide AMR surveillance program, and to raise awareness
among producers and consumers on issues of AMR.
Moreover, irrational use of antibiotics and the illegal import of medicines need
to be strictly controlled. Equal emphasis should be given to reduce antimicrobial
use as far as possible, and immunization and vaccination program to prevent
and control the infectious diseases.
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48. Conclusion (2)
A coordinated one health surveillance initiatives on antimicrobial use and
antimicrobial resistance (AMR)- involving various players like government agencies,
medical personnel, veterinarians, livestock producers/farmers, is needed.
Healthcare professionals should be trained on AMR issues, raising awareness among
public and farmers on harmful effects of drugs to their bodies and hazards of
development of antimicrobial resistance.
Users of antimicrobials need to be made aware of harmful effects of unnecessarily
prescribed drugs and its effect on increase in problem of antibiotic resistance.
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49. References
1) KD Tripathi; Essential of Medical Pharmacology 8th Edition.
2) https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance
3) Tackling Antibiotic Resistance with Compounds of Natural Origin: A Comprehensive Review
2020 published on Biomedicines
4) Global action plan on Antimicrobial resistance 2015
5) https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance
6) Rosini R, Nicchi S, Pizza M and Rappuoli R (2020) Vaccines Against Antimicrobial
Resistance. Front. Immunol. 11:1048. doi: 10.3389/fimmu.2020.01048
7) Hoelzer et al. Vet Res (2018) 49:64 https://doi.org/10.1186/s13567-018-0560-8
8) Inhibiting conjugation as a tool in the fight against antibiotic resistance
file:///C:/Users/Owner/Downloads/ddr.21457.pdf
9) DoHS Annual report 2076/77
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50. References
10) Acharya KP, Wilson RT. Frontiers in Medicine. Antimicrobial Resistance in Nepal.
6;2019 available from https://www.frontiersin.org/article/10.3389/fmed.2019.00105
11) https://www.pnas.org/content/115/51/12902
12) Global Antibiotics Resistance Partnership report 2015; situation analysis and
recommendation 6904671627th-july-final-file-GRAP.pdf
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Other classification: according to spectrum of activity narrow spectrum: penicillin, streptomycin and broad spectrum: Tetracyclines, chloramphenicol), types of action: Bacteriostatic and bacteriocidal
Overuse and misuse of drugs leads to resistance, at the same time due to inadequate access, incomplete dosing also leads to AMR
It was pointed out as early as 1945, by Alexander Fleming, in his Nobel acceptance speech, that inappropriate use of penicillin could precipitate resistance; however, this did not become a part of the mainstream policy dialogue until the World Health Organization (WHO) released the six-pronged policy package in 2011
It was first used against serogroup B meningococcus, since then it has been used on several other bacterial vaccine.
Eg use of antibiotics in broiler … and eg
Quorum sensing acts by monitoring cell density through chemical signals that allow communication between bacteria in order to regulate the expression of genes involved in virulence, competition, pathogenicity and resistance
he Ministry of Health and Population (MoHP) formulated the 2014 National Antibiotic Treatment Guidelines [15] and the National Antimicrobial Resistance Containment Action Plan Nepal 2016 to promote rational use of antibiotics, good surveillance systems, and antibiotic stewardship [8]. Similarly, the Department of Livestock Services (DLS) introduced a policy of zero tolerance to antibiotics [3,14] to stop the use of antibiotics in animal feed.