Antimicrobial resistance in bacteria

The basics of Antimicrobial resistance and its effects and prevention.

1. Antimicrobial Resistance in Bacteria Dr. Suprakash Das Assist. Prof.

2. WELCOME TO THE TITANIC OF ANTIBIOTICS……!!!!! Alexendra Flamming Discovered the 1 st Antibiotic- Penicillin In 1928

3. Antimicrobial Agents Antimicrobials are the agents that kill or inhibit the growth of Microorganisms. They can be classified in a variety of ways- Microorganisms against which they are used- Antibacterial/ Antifungal/ Antivirals Ability to kill- - Cidal / -Static According to the source: Natural/ Chemically synthesized. According to chemical structure and mechanism of action.

4. Mechanism of Action of Antimicrobials

5. SuperBugs ….!!!

6. Antimicrobial Resistance Antimicrobial resistance refers to development of resistance to an antimicrobial agent by a microorganism. It can be of 2 types- Acquired Resistance Intrinsic Resistance Acquired Resistance- This refers to the emergence of resistance in the bacteria that are ordinarily susceptible to antimicrobial agents, by acquiring genes coding for resistance. This is the most common type of antibiotic resistance among bacteria. Intrinsic Resistance- It refers to the innate ability of a bacterium to resist a class of antimicrobial agents due to its inherent structural or functional characteristics. (Gram-negative bacteria are resistant to Vancomycin.) This imposes negligible threat as it is a defined pattern of resistance and is non-transferable. However, clinicians must be aware to exclude these antibiotics from therapy.

7. Intrinsic Antimicrobial Resistance Organism Intrinsic Resistance to Antibiotics Enterobacteriaceae Antibiotics used for Gram Positive Organisms- Exception- Salmonella and Shigella is susceptible to Azithromycin K. pneumoniae Ampicillin, Ticarcillin Citrobacter spp. Ampicillin, 1 st and 2 nd gen. Cephalosporins, Cephamycins , Amoxicillin- Clavulunate / Sulbactum Proteus/ Morganella / Providentia spp./Serratia marcescens Ampicillin, 1 st and 2 nd gen. Cephalosporins, Tetracyclin , Tigecyclin , Nitrofurantoin, Polymyxin-B/E, Colistin Salmonella spp. Aminoglycosides, 1 st and 2 nd gen. Cephalosporins Y. enterocolitica Ampicillin, 1 st and 2 nd gen. Cephalosporins, Cephamycins , Amoxicillin- Clavulunate / Sulbactum , Ticarcillin.

8. Intrinsic Antimicrobial Resistance Intrinsic Antimicrobial Resistance Organism Intrinsic Resistance to Antibiotics Non- Fermentive Gram Negative Bacteria (NF-GNB) Antibiotics for Gram positive organisms + Penicillin , 1 st and 2 nd Gen. Cephalosporins. P. aeruginosa Ampicillin, Ceftriaxone, Amoxicillin-clavulanate, Ampicillin-Sulbactam, Ertapenem, Cotrimoxazole, Tigecyclin , Chloramphenicol. baumannii “do” + Fosfomycin S. maltophilia / Burkhulderia cephacia complex “do” + Polymyxin + Colistin Enterococcus gallinerum / casseliflavus Vancomycin Enterococcus spp Clindamycin, Cotrimoxazole

9. Mutational and Transferable Drug Resistance In presence of selective antibiotic pressure , bacteria acquire new genes mainly by 2 broad methods:  Mutational Resistance- Resistance can develop due to mutation of the resident genes. Typically seen in M. tuberculosis, developing resistance to ATT. Usually, it is a low level resistance, developing to one drug at a time which can be overcome by using combination of different classes of antibiotics. This is why multi drug therapy is used in ATT. Transferable drug resistance- It is plasmid coded and usually transferred by Conjugation and rarely by Transduction or Transformation. The resistance coded plasmid (usually called –R plasmid) can carry multiple genes, each coding resistance to one class of antibiotic. It results in high degree of resistance to multiple drugs which can not be overcome by combination of drugs.

10. What causes Emergence of Antimicrobial Resistance Overuse and misuse of antimicrobial agents is the single most important cause. The evaluation of resistant strains is a natural phenomenon especially when an antibiotic is overused. Use of a particular antibiotic posses selective pressure in a population of bacteria which in turn promotes resistant bacteria to thrive and susceptible bacteria to die off. Thus resistant population flourish in the area of high antimicrobial use. Other important drivers of spread of antimicrobial resistance  Lack of access to clean water Sanitation and hygiene for both humans and animals Poor infection control practices in health care facilities. Poor access to quality and affordable medicines and diagnostics Lack of awareness and knowledge Lack of legislation.

11. Deaths due to Antimicrobial Resistance by 2050- A Forecast

12. Mechanism of Antimicrobial Resistance  Decreased permeability across cell wall Certain bacteria modify their cell wall membrane porin channels, either in frequency, size, or selectivity, thereby, preventing antimicrobials into entering in to the cell. Bacteria- Pseudomonas, Enterobacter and Klebsiella spp. Antibiotics- Imipenem, Aminoglycosides, Quinolones. Efflux Pumps Efflux pumps mediate expulsion of drugs from the cells, soon after their entry, thereby preventing the intra-cellular accumulation of drugs. E. coli and Enterobacteriaceae- Tetracycline and Chloramphenicol Staphylococci- Macrolides S. aureus and S. pneumoniae - Fluoroquinolones

13. Mechanism of Antimicrobial Resistance  Enzymatic Inactivation Certain bacteria can inactive the antimicrobial agent by producing various enzymes such as: Beta Lactamases- Produced by both Gram + ve & - ve organisms. Acts on Beta lactam drugs by breaking the Beta lactam ring. Aminoglycoside modifying enzymes (Acetyl/ Adenyl and Phospho-Transferases) Chloramphenicol Acetyl Transferase- Produced by Enterobacteriaceae. Modification of Target Sites MRSA (Methicillin Resistant Sthaphylococcus aureus )- In this strain, the binding site for Penicillin (PBP) get altered to PBP-2a coded by gene mec A . tHIS altered protein don’t bind penicillin and resist the cell wall formation inhibition by penicillin.

14. Mechanism of Antimicrobial Resistance  Pneumococci- B- lactam resistance due to altered PBP (PBP-2b) Streptomycin resistance in Mycobacteria due to altered 16s rRNA protein. Rifampicin resistance- Mutation in RNA polymerase Quinolone resistance- Mutation in RNA gyrase enzymes Vancomycin Resistant Enterococci- cHANGES in target site for Vancomycin.

15. Vancomycin Resistance 

16. Laboratory Testing for Antimicrobial Resistance- Kirby- Baurer Disc Diffusion Method

17. Laboratory Testing for Antimicrobial Resistance- Broth Micro Dilution Method

18. Laboratory Testing for Antimicrobial Resistance- E-test

19. Laboratory Testing for Antimicrobial Resistance- Automated ID & AST

20. Gene Sequencing for Antimicrobial Resistance

21. Line Probe Assay ATT Drugs Resistance Diagnosis

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