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.

6. 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

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

8. 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.

9. 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

10. 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

11. 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)

12. 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

14. MECHANISM OF RESISTANCE
 Drug Impermeable
 Drug Destroying
 Drug Tolerant

15. DRUG IMPERMEABLE
 Decrease permeability
 Efflux Pump

17. 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.

18. 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

19. Aminoglycoside modifying enzymes
 Acetyltransferases
 Adenyltransferases
 Phosphotransferases
Other enzymes
Chloramphenicol acetyl transferase produced by members
of Enterobacteriaceae; destroys the structure of
chloramphenicol.

20. 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

21. 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.

22. 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

29. 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%

30. 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