ANTIMICROBIAL RESISTANCE

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.

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 Sir Alexander Fleming The Nobel Prize in Physiology or Medicine, 1945 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. Stuart B. Levy researcher and physician at Tufts University, 1997

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 .: Mycobacterium tuberculosis is resistant to tetracycline. Aerobic organisms are not affected by metronidazole. 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 [1] Velez R, Sloand E. Combating antibiotic resistance, mitigating future threats and ongoing initiatives. J Clin Nurs 2016 ;(March). [2] Akova M. Epidemiology of antimicrobial resistance in bloodstream infections. Virulence 2016;(March). [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.

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