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ANTIMICROBIAL RESISTANCE-CURRENT SCENARIO IN INDIA,
MECHANISM OF DEVELOPMENT & SOLUTION TO AMR
PRESENTED BY – DR. GOBINDA PRASAD PRADHAN
GUIDED BY - DR. NIBEDITA PRADHAN, ASST. PROF.
POINTS TO BE DISCUSSED
• INTRODUCTION
• DEFINITION
• CURRENT BURDEN IN INDIA
• TYPES & MECHANISM OF AMR
• THREATS
• SOLUTION
• TAKE HOME MESSAGE
Antimicrobial resistance occurs when
microorganisms such as bacteria, viruses, fungi and
parasites change in ways that render the
medications used to cure the infections they cause
ineffective. When the microorganisms become
resistant to most antimicrobials they are often
referred to as “SUPERBUGS”
ANTIMICROBIAL RESISTANCE
WHO DEFINITION
• Antimicrobial resistance is a broader term, encompassing
resistance to drugs that treat infections caused by microbes
such as bacteria, parasites (e.g. malaria or helminths), viruses
(e.g. HIV) and fungi (e.g. Candida).
• Antibiotic resistance occurs when bacteria change in response
to the use of antibiotics used to treat bacterial infections (such
as urinary tract infections, pneumonia, bloodstream infections)
making them ineffective.
Difference between Antimicrobial and Antibiotic Resistance
• A person cannot become resistant to antibiotics. Resistance is a
property of the microbe, not a person or other organism infected by
a microbe
• The major problem threatening the continued success of
antimicrobial drugs is the development of resistant organisms.
• Because resistance mechanisms are already present in nature, an
inevitable consequence of antimicrobial use is the selection of
resistant microorganisms.
PROBLEMS
• Duration of treatment Increases
• The prevalence of resistant organisms drives the use of broader-spectrum,
less efficacious, or more toxic antibiotics.
• Not surprisingly, infections caused by antibiotic-resistant pathogens are
associated with increased costs, morbidity, and mortality.
WHO SURVEY
• The 2015 WHO multi-country survey revealed
widespread public misunderstanding about antibiotic
usage and resistance. The survey highlights for India are
of concern:
• Three quarters (75%) of respondents think, incorrectly,
that colds and flu can be treated with antibiotics; and
only 58% know that they should stop taking antibiotics
only when they finish the course as directed.
• More than three quarters (76%) of respondents report
having taken antibiotics within the past 6 months; 90%
say they were prescribed or provided by a doctor or
nurse.
• While 75% agree that antibiotic resistance is one of the
biggest problems in the world, 72% of respondents
believe experts will solve the problem before it becomes
too serious.
CLINICAL SIGNIFICANCE
• Linked with the volume of antibiotic prescribed
• Missing doses
• Inappropriate prescribing of antibiotics
 such as patients insisting on antibiotics and
physicians prescribing them as they do not have time
to explain why they are not necessary.
 Another cause can be physicians not knowing when
to prescribe antibiotics or being overly cautious for
medical or legal reasons.
• Lower antibiotic concentration contributes to the increase
of AMR
DIARRHEA
VIRUS OTHER ANTIBIOTIC TREATED
70%
30%
40%
Inappropriate use of medicines
• Overuse
• Underuse and
• Misuse of medicines
Lack of quality medicines
• Sub-optimal concentrations of antimicrobials
• In some countries poor access to
antimicrobials forces patients to take
incomplete courses of treatment or to seek
alternatives that could include substandard
medicines
Animal husbandry
• Sub-therapeutic doses of antibiotics are used
in animal-rearing for promoting growth or
preventing diseases.
• This can result in resistant microorganisms,
which can spread to humans.
Poor infection prevention &
control
• Hospitalized patients are one of the main
reservoirs of resistant microorganisms.
• Patients who are carriers of resistant
microorganisms can act as a source of
infection for others.
Deaths attributable to antimicrobial resistance every year compared to
other major causes of death
https://resistancemap.cddep.org/CountryPage.php?countryId=17&country=India
https://resistancemap.cddep.org/CountryPage.php?countryId=17&country=India
https://resistancemap.cddep.org/CountryPage.php?countryId=17&country=India
https://resistanceopen.org
DRUG RESISTANCE • NATURAL RESISTANCE
• AQUIRED RESISTANCE
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.
• This is generally a group or species
characteristic
• e.g. gram-negative bacilli are normally
unaffected by penicillin G; aerobic organisms
are not affected by metronidazole; while
anaerobic bacteria are not inhibited by
aminoglycoside antibiotics, or M. tuberculosis is
insensitive to tetracyclines.
• This type of resistance does not pose a
significant clinical problem.
AQUIRED RESISTANCE
• It is the development of resistance by an organism
(which was sensitive before) due to the use of an
AMA over a period of time.
• This is a major clinical problem
• However, development of resistance is dependent
on the microorganism as well as on the drug.
• Development of acquired resistance may be due to
single step mutation (as seen with streptomycin &
rifampicin) or Multistep mutation (Erythromycin,
Tetracycline, Chloramphenicol)
Resistance may be developed by
• Mutation or Gene Transfer
MUTATION
• Any sensitive population of a microbe contains a few
mutant cells which require higher concentration of the
AMA for inhibition.
• These are selectively preserved and get a chance to
proliferate when the sensitive cells are eliminated by
the AMA. Thus, in time it would appear that a
sensitive strain has been replaced by a resistant one
• e.g. when a single antitubercular drug is used.
• This is called vertical transfer of resistance; is relatively
slow and usually of lower grade.
GENE TRANSFER (INFECTIOUS RESISTANCE)
THE RESISTANCE CAUSING GENE IS PASSED FROM
ONE ORGANISM TO THE OTHER; IS CALLED
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.
Gene transfer can be by
1. CONJUGATION
2. TRANSDUCTION
3. TRANSFORMATION
CONJUGATION
Sexual contact through the formation of a bridge or sex pilus is
common among gram-negative bacilli of the same or another species.
Chloramphenicol resistance of typhoid bacilli, streptomycin resistance
of E. coli, penicillin resistance of Haemophilus and gonococci and many
others have been traced to this mechanism.
TRANSDUCTION
The R factor is taken up by the phage and delivered to another
bacterium which it infects.
Many Staph. aureus strains have acquired resistance by
transduction.
Certain instances of penicillin, erythromycin and chloramphenicol
resistance have been found to be phage mediated.
TRANSFORMATION
A resistant bacterium may release the resistance carrying DNA into the
medium and this may be imbibed by another sensitive organism—
becoming unresponsive to the drug.
This mechanism is probably not clinically significant.
e.g. Penicillin G
Antimicrobial resistance can develop at any one or more steps in the process by which a
drug reaches & combines with its target. Thus, resistance development may develop
due to:
1. Reduced entry of antibiotic into pathogen
2. Enhanced export of antibiotic by efflux pumps
3. Release of microbial enzymes that destroy the antibiotic
4. Alteration of microbial proteins that transform pro-drugs to
the effective moieties
5. Alteration of target proteins
6. Development of alternative pathways to those inhibited by
the antibiotic
Duration of antibiotics Monitoring and Mapping
Limiting antibiotics use at different levels
HOSPITAL LEVEL FARMING LEVEL LEVEL OF GP INDIVIDUAL LEVEL
WASH
WATER SANITATION HYGIENE
INDUSTRIAL
WASTEWATER
TREATMENT
MANAGEMENT IN
ANIMAL USE
GLOBAL ACTION
PLANS AND
AWARENESS
POLICY VACCINATION
• Development of new drugs
• Monoclonal Ab
• Phage therapy
Phage therapy
• Phage therapy is the therapeutic use of bacteriophage to
treat pathogenic bacterial infections.
• New research analyzes the effect of cigarette smoke on MRSA strains
and finds that it makes the bacteria more persistent, more invasive,
and more resistant to certain antibiotics.
• The probiotic that kills antibiotic-resistant bacteria- bacillus subtilis.
At the 68th World Health Assembly in May 2015, the World Health Assembly endorsed a
GAP to tackle antimicrobial resistance, including antibiotic resistance, the most urgent
drug resistance trend.
National Action Plan
on Antimicrobial Resistance
(NAP-AMR) 2017 – 2021
https://www.eurekalert.org/pub_releases/2018-12/su-bfi122718.php
https://longitudeprize.org/blog-post/qa-new-rapid-credit-card-sized-uti-test-women-0
RIGHT FOR RIGHT
TAKE HOME MESSAGE
REFERENCES
• https://resistancemap.cddep.org/
• https://resistanceopen.org
• Goodman & Gilman’s pharmacological basis of therapeutics, 12th edition
• WHO
AMR in India: Current Scenario, Mechanisms, Solutions & Threats
AMR in India: Current Scenario, Mechanisms, Solutions & Threats

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AMR in India: Current Scenario, Mechanisms, Solutions & Threats

  • 1. ANTIMICROBIAL RESISTANCE-CURRENT SCENARIO IN INDIA, MECHANISM OF DEVELOPMENT & SOLUTION TO AMR PRESENTED BY – DR. GOBINDA PRASAD PRADHAN GUIDED BY - DR. NIBEDITA PRADHAN, ASST. PROF.
  • 2. POINTS TO BE DISCUSSED • INTRODUCTION • DEFINITION • CURRENT BURDEN IN INDIA • TYPES & MECHANISM OF AMR • THREATS • SOLUTION • TAKE HOME MESSAGE
  • 3.
  • 4. Antimicrobial resistance occurs when microorganisms such as bacteria, viruses, fungi and parasites change in ways that render the medications used to cure the infections they cause ineffective. When the microorganisms become resistant to most antimicrobials they are often referred to as “SUPERBUGS” ANTIMICROBIAL RESISTANCE WHO DEFINITION
  • 5. • Antimicrobial resistance is a broader term, encompassing resistance to drugs that treat infections caused by microbes such as bacteria, parasites (e.g. malaria or helminths), viruses (e.g. HIV) and fungi (e.g. Candida). • Antibiotic resistance occurs when bacteria change in response to the use of antibiotics used to treat bacterial infections (such as urinary tract infections, pneumonia, bloodstream infections) making them ineffective. Difference between Antimicrobial and Antibiotic Resistance
  • 6. • A person cannot become resistant to antibiotics. Resistance is a property of the microbe, not a person or other organism infected by a microbe • The major problem threatening the continued success of antimicrobial drugs is the development of resistant organisms. • Because resistance mechanisms are already present in nature, an inevitable consequence of antimicrobial use is the selection of resistant microorganisms.
  • 7. PROBLEMS • Duration of treatment Increases • The prevalence of resistant organisms drives the use of broader-spectrum, less efficacious, or more toxic antibiotics. • Not surprisingly, infections caused by antibiotic-resistant pathogens are associated with increased costs, morbidity, and mortality.
  • 8. WHO SURVEY • The 2015 WHO multi-country survey revealed widespread public misunderstanding about antibiotic usage and resistance. The survey highlights for India are of concern: • Three quarters (75%) of respondents think, incorrectly, that colds and flu can be treated with antibiotics; and only 58% know that they should stop taking antibiotics only when they finish the course as directed. • More than three quarters (76%) of respondents report having taken antibiotics within the past 6 months; 90% say they were prescribed or provided by a doctor or nurse. • While 75% agree that antibiotic resistance is one of the biggest problems in the world, 72% of respondents believe experts will solve the problem before it becomes too serious.
  • 9. CLINICAL SIGNIFICANCE • Linked with the volume of antibiotic prescribed • Missing doses • Inappropriate prescribing of antibiotics  such as patients insisting on antibiotics and physicians prescribing them as they do not have time to explain why they are not necessary.  Another cause can be physicians not knowing when to prescribe antibiotics or being overly cautious for medical or legal reasons. • Lower antibiotic concentration contributes to the increase of AMR
  • 10. DIARRHEA VIRUS OTHER ANTIBIOTIC TREATED 70% 30% 40%
  • 11. Inappropriate use of medicines • Overuse • Underuse and • Misuse of medicines
  • 12. Lack of quality medicines • Sub-optimal concentrations of antimicrobials • In some countries poor access to antimicrobials forces patients to take incomplete courses of treatment or to seek alternatives that could include substandard medicines
  • 13. Animal husbandry • Sub-therapeutic doses of antibiotics are used in animal-rearing for promoting growth or preventing diseases. • This can result in resistant microorganisms, which can spread to humans.
  • 14. Poor infection prevention & control • Hospitalized patients are one of the main reservoirs of resistant microorganisms. • Patients who are carriers of resistant microorganisms can act as a source of infection for others.
  • 15.
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  • 21. Deaths attributable to antimicrobial resistance every year compared to other major causes of death
  • 25.
  • 27. DRUG RESISTANCE • NATURAL RESISTANCE • AQUIRED RESISTANCE
  • 28. 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. • This is generally a group or species characteristic • e.g. gram-negative bacilli are normally unaffected by penicillin G; aerobic organisms are not affected by metronidazole; while anaerobic bacteria are not inhibited by aminoglycoside antibiotics, or M. tuberculosis is insensitive to tetracyclines. • This type of resistance does not pose a significant clinical problem.
  • 29. AQUIRED RESISTANCE • It is the development of resistance by an organism (which was sensitive before) due to the use of an AMA over a period of time. • This is a major clinical problem • However, development of resistance is dependent on the microorganism as well as on the drug. • Development of acquired resistance may be due to single step mutation (as seen with streptomycin & rifampicin) or Multistep mutation (Erythromycin, Tetracycline, Chloramphenicol)
  • 30. Resistance may be developed by • Mutation or Gene Transfer
  • 31. MUTATION • Any sensitive population of a microbe contains a few mutant cells which require higher concentration of the AMA for inhibition. • These are selectively preserved and get a chance to proliferate when the sensitive cells are eliminated by the AMA. Thus, in time it would appear that a sensitive strain has been replaced by a resistant one • e.g. when a single antitubercular drug is used. • This is called vertical transfer of resistance; is relatively slow and usually of lower grade.
  • 32. GENE TRANSFER (INFECTIOUS RESISTANCE) THE RESISTANCE CAUSING GENE IS PASSED FROM ONE ORGANISM TO THE OTHER; IS CALLED 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.
  • 33. Gene transfer can be by 1. CONJUGATION 2. TRANSDUCTION 3. TRANSFORMATION
  • 34. CONJUGATION Sexual contact through the formation of a bridge or sex pilus is common among gram-negative bacilli of the same or another species. Chloramphenicol resistance of typhoid bacilli, streptomycin resistance of E. coli, penicillin resistance of Haemophilus and gonococci and many others have been traced to this mechanism.
  • 35. TRANSDUCTION The R factor is taken up by the phage and delivered to another bacterium which it infects. Many Staph. aureus strains have acquired resistance by transduction. Certain instances of penicillin, erythromycin and chloramphenicol resistance have been found to be phage mediated.
  • 36. TRANSFORMATION A resistant bacterium may release the resistance carrying DNA into the medium and this may be imbibed by another sensitive organism— becoming unresponsive to the drug. This mechanism is probably not clinically significant. e.g. Penicillin G
  • 37. Antimicrobial resistance can develop at any one or more steps in the process by which a drug reaches & combines with its target. Thus, resistance development may develop due to: 1. Reduced entry of antibiotic into pathogen 2. Enhanced export of antibiotic by efflux pumps 3. Release of microbial enzymes that destroy the antibiotic 4. Alteration of microbial proteins that transform pro-drugs to the effective moieties 5. Alteration of target proteins 6. Development of alternative pathways to those inhibited by the antibiotic
  • 38.
  • 39. Duration of antibiotics Monitoring and Mapping
  • 40. Limiting antibiotics use at different levels HOSPITAL LEVEL FARMING LEVEL LEVEL OF GP INDIVIDUAL LEVEL
  • 42. INDUSTRIAL WASTEWATER TREATMENT MANAGEMENT IN ANIMAL USE GLOBAL ACTION PLANS AND AWARENESS POLICY VACCINATION
  • 43. • Development of new drugs • Monoclonal Ab • Phage therapy
  • 44. Phage therapy • Phage therapy is the therapeutic use of bacteriophage to treat pathogenic bacterial infections.
  • 45. • New research analyzes the effect of cigarette smoke on MRSA strains and finds that it makes the bacteria more persistent, more invasive, and more resistant to certain antibiotics. • The probiotic that kills antibiotic-resistant bacteria- bacillus subtilis.
  • 46.
  • 47. At the 68th World Health Assembly in May 2015, the World Health Assembly endorsed a GAP to tackle antimicrobial resistance, including antibiotic resistance, the most urgent drug resistance trend.
  • 48. National Action Plan on Antimicrobial Resistance (NAP-AMR) 2017 – 2021
  • 49.
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  • 56. REFERENCES • https://resistancemap.cddep.org/ • https://resistanceopen.org • Goodman & Gilman’s pharmacological basis of therapeutics, 12th edition • WHO