Antimicrobial resistance

Antibiotic, Type, MOA, Cross resistance, Cause, Prevention, New Therapy

1. Presented By: Dr Sumesh Kumar DASH 1st Year PG Resident Moderator: Dr (Prof) Kundan Kumar Sahu HOD Dept of Microbiology IMS & SUM Hospital, BBSR

2. INTRODUCTION DEFINITION WHY RESISTANCE IS A CONCERN TYPE MECHANISM OF RESISTANCE CROSS-RESISTANCE CAUSES PREVENTION NEW THERAPY

3. INTRODUCTION

4. DEFINITION Antimicrobials are the agents that kill or inhibit the growth of Microorganism. The ability of bacteria and other microorganisms to resists the effect of an antimicrobial agents (AMAs) is called Antimicrobial Resistance.

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

6. TYPE Some are born great, some achieve greatness or some have greatness thrust upon them. Intrinsic resistance Acquired resistance

7. INTRINSIC RESISTANCE Some microbes have always been resistant to certain AMAs . These microbes probably lack of metabolic process or the target site which is usually affected by the drug. This is generally a group or species characteristic. This type of resistance doesn’t pose significant clinical problem.

8. ACQUIRED RESISTANCE Refers to develop resistance by an organism, which was sensitive before, due to acquiring gene coding for resistance time. It depends on microbes as well as drug. Major clinical problem. Mutational Resistance Gene Transfer Resistance

9. Mutational Resistance It is a stable & heritable genetic change that occur spontaneously & randomly among microorganisms. Not induced by AMAs Seen in M.tuberculosis , resistance to anti-tubercular drug Overcome by combination of drugs. 2 Type Single step Multi step

10. Gene Transfer Resistance AKA Infectious resistance. Plasmid are responsible for this type of resistance. Very important from a clinical point of view : Occurs in many different species Frequently mediate resistance to multiple drugs High rate of transfer from one cell to another.( Horizontal transfer)

11. Horizontal transfer Genetic exchange between resistant and non- resistant susceptible strains. More commonly determinant “R” factor from donor to recipient cell of the same species or often to another bacterial species Conjugation Transduction Transformation

12. MECHANISM OF RESISTANCE Drug Impermeable Drug Destroying Drug Tolerant

13. DRUG IMPERMEABLE Decrease permeability Efflux Pump

14. Efflux pump Certain bacteria possess efflux pumps which mediate expulsion of the drug(s) from the cell, soon after their entry; thereby preventing the intracellular accumulation of drugs. Enterobacteriaceae against tetracyclines, chloramphenicol Staphylococci against macrolides and streptogramins Staphylococcus aureus and Streptococcus pneumoniae against fluoroquinolones.

15. DRUG DESTROYING The resistant microbe elaborates an enzyme which inactivates the drug(s). β lactamase enzyme production: It breaks down the B lactam rings, there by inactivating the β lactam antibiotics. Enzyme present in low quantity but located periplasmically (as in gram-negative bacteria),drug is inactivated soon after entry. Present in large quantities (by gram- positive bacteria) which diffuse into the surrounding and destroy the drug before entry.  Enzymes Penicillinases Cephalosporinase ESBL Carbapenemease

16. Aminoglycoside modifying enzymes A cetyltransferases Adenyltransferases Phosphotransferases Other enzymes Chloramphenicol acetyl transferase produced by members of Enterobacteriaceae; destroys the structure of chloramphenicol.

17. DRUG TOLERANT Loss of affinity of the target site of the microorganism for a particular AMA. Penicillin–Binding Protein (PBP) PBP gets altered to PBP-2a by a chromosomally coded gene mec A. PBP-2a is insufficient to bind B-lactam. DNA gyrase Quinolone resistance seen in many gram-positive bacteria. RNA Polymerase Rifampicin resistance in Mycobacterium tuberculosis. 16S rRNA Streptomycin resistance in Mycobacterium tuberculosis

18. CROSS-RESISTANCE Acquisition of resistance to one AMA conferring resistance to another AMA, to which the organism has not been exposed., is called cross resistance. These are seen in Drugs that share a mechanism of action Chemically Related drugs Similar mode of binding or action Two-way , e.g. erythromycin and clindamycin and vice versa, or One-way , e.g. development of neomycin resistance by Enterobacteriaceae makes them insensitive to streptomycin but many streptomycin resistant organisms remain susceptible to neomycin.

19. ANTIBIOTIC RESISTANT BACTERIA ESBL MBL MRSA ( mec A, mec C ) BORSA (Hyperproduction of B lactamase) VISA (Cell wall thickness ) VRSA ( van A ) VRE ( van gene ) MDR TB XDR TB

20. PHAGE THERAPY Phage therapy involves the use of viruses that attack bacteria to treat pathogenic bacterial infections.  The advantage of such viruses, known as bacteriophages or phages, is that they selectively target and destroy certain bacteria without harming the host organism or other beneficial bacteria . Most therapies use lytic phages, which take over the machinery of the bacterial cell and then destroy the cell. The success rate was 80–95%

21. Comparison between antibiotics and phage therapy ANTIBIOTIC PHAGES SPECIFICITY broad spectrum of both pathogenic and harmless microorganisms. specific strains of bacteria without disrupting the microbial balance SIDE-EFFECT Secondary infections No serious side effects DOSAGE Multiple doses Fewer doses RESISTANCE More common Uncommon  DEVELOPMENT Several years days or weeks COST Less cost Costly