This document discusses drug resistance. It introduces factors and mechanisms of drug resistance, including intrinsic, acquired, genetic and biochemical mechanisms. It also discusses control strategies like judicious antibiotic use and developing new drugs. Drug resistance occurs via mutation, gene transfer between bacteria, and modifying drug targets, accumulation, or inactivating enzymes. Proper antibiotic use and waste management can help control the growing threat of antimicrobial resistance.

1. DRUG RSISTANCE
VMC-601
Dr. Bhagraj Godara
Bishnoi_rj19 (thanks me on insta)

2. OBJECTIVES
 Introduction
 Factors of Drug resistance
Mechanism of Drug resistance
Control Strategy
Conclusion

3. INTRODUCTION
 Drug resistance is the ability of microbes
such as bacteria , virus or fungi to grow in
the presence of a drug that would normally
kill it or inhibit its growth.

4. FACTORS OF DR
Drug related factors
Environmental factors
Patient related factors

5. MECHANISM OF DR
A)Intrinsic/Natural
B)Acquired
 Genetic method:
.Chromosomal methods – Mutation
.Extra-chromosomal methods - Plasmids
.Transfer of r-Genes from bacterium to other –
Conjugation ,Transduction , Transformation
.Transfer of r-Genes between plasmids within
bacteria
By Transposons , By Integron

6. Cont..
 Biochemical Mechanism:
I. Production of inactivating enzymes
II. Preventing drug accumulation within bacterium
III. Modifying target sites
IV. Use of alternative pathways for metabolism

7. INTRINSIC/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’s.
 Aerobic organisms are not affected by Metronidazole.
 Gram –ve bacilli are normally unaffected by penicillin G.

8. 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. BIOCHEMICAL MECHANISMS
By producing Antibiotic inactivating enzymes
i. Staphylococcus aureus , Neisseria gonorrhoea, Haemophilus
influenzae and some enteric Gram negative rods produce β
lactamase enzyme which cleaves the β lactam ring thereby
inactivating β lactam antibiotics.
ii. Some Gram –ve and Gram +ve bacteria inactivates
Chloramphenicol by the enzyme chloramphenicol
acetyltransferase (plasmid mediated).
iii. Inactivation of Aminoglycosides by some Gram –ve and Gram
+ve bacteria are mediated by the enzymes acetyltransferases,
phospotransferases and adenylyltransferases .

11. By preventing drug accumulation within bacterium
i. It is mediated either by promoting efflux or by
preventing the influx of the drug.
ii. Efflux pumps (chromosomal or plasmid-mediated)
are cytoplasmic membrane transport proteins
which commonly operates in E. coli, P.aeruginosa
,S.typhi, S.aureus, Stretpto. pyogenes, Strepto.
Pneumoniae, N. gonorrhoeae, mycobacteria and
enterococci.
iii. These efflux pumps are the major mechanism of
resistance for tetracyclines, fluoroquinolones and
erythromycin.

13. By modifying the target site
i. Ribosomal point mutations for Tetracyclines,
Macrolides and Clindamycin.
ii. Altered DNA gyrase and Topoisomerase for
fluoroquinolones.
iii. Modified penicillin binding protein in
Streptococcous pneumoniae leading to penicilline
resistance.

15. By Use of alternative pathways for Metabolism
i. Resistance to antibiotics can be conferred by
developing an alternative pathway that bypasses the
reaction by the antibiotic.
Eg:
Sulphonamide resistance occurs from overproduction
of PABA.
Some enteric organisms evade beta-lactam antibiotic
by overproducing beta-lactamases.

16. CONTROL STRATEGY
Judicious use of Existing Antimicrobial agents.
Development of New Antimicrobial agents.

17. CONCLUSION
 Anti microbial resistance is an emerging global
threat.
 Strategies to prevent development of antimicrobial
resistance should be devised.
 Judicious useof antimicrobial agents by health care
professional and general population.
 Proper pharmaceutical waste management.