This document discusses antimicrobial resistance and provides definitions, history, and mechanisms. It defines antimicrobial resistance as the ability of microorganisms like bacteria, viruses, and parasites to stop antimicrobial drugs from working against them. The discovery of antimicrobials created new treatments but microbes developed resistance over time. Factors that contribute to resistance include overuse of antibiotics, lack of sanitation, and transmission of resistant genes between bacteria. Resistance occurs via natural and acquired mechanisms, the latter being a major clinical problem. Strategies to address resistance include prudent antibiotic use, developing new drugs, and alternative approaches like phage therapy.

1. Journal Club
Antimicrobial
resistance
By- Kushal Saha

2. Contents
• Introduction.
• History.
• Timeline.
• Why resistance is a concern?
• Factors.
• Mechanisms.
• Control strategy.
• Conclusion

3. DEFINITION: Antimicrobial resistance is the ability of a
microorganism (like bacteria, viruses, and some parasites) to stop
an antimicrobial (such as antibiotics, antivirals and antifungals)
from working against it.
Discovery of anti-microbial agents created a new era in the field
of Medical Science.
Microbes, on the other hand, developed various mechanisms to
counter this threat to their existence.
Antimicrobial drug resistance is the ability of a microbe to resist
the effects of medication which was previously used to treat
them.
This is responsible for millions of death worldwide and is
considered as a major health concern nowadays.
Antimicrobial resistance (AMR) threatens the effective
prevention and treatment of an ever- increasing range of
infections caused by the microbes.
The cost of health care for patients with resistant infections is
higher.
Introduction

4. History
It is not difficult to make microbes
resistant to penicillin in the laboratory by
exposing them to concentrations not
sufficient to kill them, and the same
thing has occasionally happened in the
body and by exposing his microbes to
non-lethal quantities of the drug make
them resistant.
The consequence of antibiotic use is,
therefore, the disruption of the natural
microbial ecology. This alteration may be
revealed in the emergence of types of
bacteria which are very different from
those previously found there, or drug
resistant variants of the same ones that
were already present.

5. Timeline
Antibiotic Discovered Introduced into Clinical Use Resistance Identified
Penicillin 1940 1943 1940
Streptomycin 1944 1947 1947
Tetracycline 1948 1952 1956
Erythromycin 1952 1955 1956
Vancomycin 1956 1972 1987
Gentamycin 1963 1967 1970

6. Why resistance is a concern?
• Resistant organisms lead to treatment failure
• Increased mortality
• Resistant bacteria may spread in Community
• Low level resistance can go undetected
• Added burden on healthcare costs
• Threatens to return to pre-antibiotic era
• Selection pressure

7.  Environmental Factors:
• Huge populations and overcrowding.
• Rapid spread due to better
transport facilities.
• Poor sanitation.
• Increase in community acquired
resistance.
• Ineffective infection control
program.
• Widespread use of antibiotics in
animal husbandry and agriculture
and as medicated cleansing
products.
• Release of large quantities of
antibiotics into the environment
during pharmaceutical
manufacturing through inadequate
wastewater treatment.
 Drug Related Factors:
• Over the counter availability of
antimicrobials.
• Counterfeit and substandard drug
causing sub- optimal blood
concentration.
• Irrational fixed dose combination of
antimicrobials.
• Increasing use of antibiotics.
 Patient Related Factors:
• Poor adherence of dosage Regimens.
• Poverty.
• Lack of sanitation concept.
• Lack of education.
• Self-medication.
 Prescriber Related Factors:
• Inappropriate use of antibiotics.
• Increased empiric poly-
antimicrobial use.
• Overuse of antimicrobials.
• Prolonged use of antimicrobials.
• Inadequate dosing.
• Lack of current knowledge and
training.
Factors

8. MECHANISMS OF Antimicrobial resistance
 INTRINSIC OR 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 type of resistance does not pose significant clinical problem.
E.g.:
i. Mycobacterium tuberculosis is resistant to tetracycline.
ii. Aerobic organisms are not affected by metronidazole.
iii. Gram –ve bacilli are normally unaffected by penicillin G.
 ACQUIRED RESISTANCE:
• It is the development of resistance by an organism (which was earlier sensitive)
due to the use of an AMAs over a period of time.
• This can happen with any microbes and is a major clinical problem .
• This type of resistance develops either by gene transfer or by mutation or by
modification in biochemical mechanisms.

9.  Genetic Methods:
• Chromosomal Methods (Mutations)
• Extra chromosomal Methods (Plasmids)
 Mutations
• It refers to the change in DNA structure of the gene.
• Occurs at a frequency of one per ten million cells.
• E.g.. Mycobacterium tuberculosis, Mycobacterium lepra.
• Often mutants have reduced susceptibility
 Plasmids:
Extra chromosomal genetic elements can replicate independently and freely
in cytoplasm.
• Plasmids which carry genes resistant (r-genes) are called R plasmids.
• These r-genes can be readily transferred from one R-plasmid to another
plasmid or to chromosome.
• Much of the drug resistance encountered in clinical practice is plasmid
mediated

10. A natural population of bacteria has some that are susceptible and some that are resistant

11. You start taking an antibiotic…

12. And the susceptible (weak) bacteria die first

13. You keep taking the antibiotic, more bacteria die

14. Until eventually only the resistant bacteria are left

15. You stop taking the antibiotic

16. The resistant bacteria reproduce

17. The resistant bacteria grows more

18. Now there are lots of resistant bacteria

19. If we take the antibiotic again, what happens?

20. Nothing! All the bacteria are resistant!

21. STRATEGY TO CONTAIN AMR
• Judicious use of Existing Anti- microbial Agents.
• Development of new Anti–microbial Agents.
NEWER APPROACHE:
 Phage Therapy:
• Phage Therapy is the therapeutic use of lytic bacteriophages to treat
pathogenic bacterial infections.
• Bacteriophage therapy can be an important alternative to antibiotics.
• The success rate was 80–95% with few gastrointestinal or allergic
side effects.
• British studies also demonstrated significant efficacy of phages
against Escherichia coli, Acinetobacter spp., Pseudomonas spp. and
Staphylococcus aureus.

22. CONCLUSION
• Anti microbial resistance is an emerging global threat.
• Strategies to prevent development of antimicrobial resistance should
be devised.
• Judicious use of antimicrobial agents by health care professionals &
general population.
• Preventing un-judicious use of antibiotics in animal husbandry and
farming practices.
• Avoiding incorporation of antibiotics in commercial cleansing products.
• Proper pharmaceutical waste management.

23. REFERENCES
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[3] Mühlen S, Dersch P. Anti-virulence strategies to target bacterial
infections. Curr Top Microbiol Immunol 2016;(March).
[4] Chellat MF, Raguˇz L, Riedl R. Targeting antibiotic resistance. Angew
Chem Int Ed Engl 2016;(March).
[5] von Wintersdorff CJ, Penders J, van Niekerk JM, Mills ND,
Majumder S, van Alphen LB, et al. Dissemination of antimicrobial
resistance in microbial ecosystems through horizontal gene transfer.
Front Microbiol 2016;7(February):173.

24. THANK YOU