ANTIMICROBIAL DRUG

RESISTANCE
Submitted by: Supervised By:
Ajay Agrawal Asstt. Prof. Shri Ram
(Enroll. No.: 06/15418)
Swami Keshvanand Institute of Pharmacy

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 Introduction

Antimicrobials

 Antimicrobial; the “magic bullet”1

 Antibiotic: Compounds produced by micro-organisms and

capable of inhibiting bacterial growth and bacterial infections1

 Antibacterials, like triclosan are also used in health concerning

commercial products2

2 1. Tripathi KD. Essentials of Medical pharmacology, fifth Edition.

2. Salyers AA and Amabile-Cuevas CF. Antimicrob Agents Chemother, 1997, 41: 2321-5
 History of Antimicrobials
 First modern antimicrobial Salvarsan,
discovered by Paul Ehrlich. It was
used to treat syphilis.
 Quinine was isolated in 1820 from the
bark of the cinchona tree: antimalarial
agent.
 Sulfonamides: Synthetic antimicrobials
were introduced in 1930. It block folic
acid production in bacteria.
 The first antibiotic (in the original
sense of the word) was penicillin,
discovered by Alexander Fleming in
1928.

3 Tripathi KD. Essentials of Medical pharmacology, fifth Edition.

 Antimicrobial Drug Resistance

 When micro-organisms are able to multiply in the

presence of drug concentrations higher than those
achievable in humans receiving therapeutic doses, it
is called antimicrobial drug resistance2

 Several factors for emergence of drug resistance3

Misuse of antimicrobials
Poor quality of available drugs

4 2. Salyers AA and Amabile-Cuevas CF. Antimicrob Agents Chemother, 1997, 41: 2321-5.
3. WHO report on infectious diseases: Removing obstacles to healthy development Geneva, 1999
 Development of Drug
Resistance; Comparison Between
Healthy and Sick Person

5 http://www3.niaid.nih.gov/
 Level of Resistance

 Resistance observed are three types

1. First line drugs: Multiple Drug Resistance

2. Second line drugs: Extremely Drug Resistance
3. Third line drugs: Completely Drug Resistance

To prevent the emergence of CDR

Fourth line drugs: Under process

6 Tripathi KD. Essentials of Medical pharmacology, fifth Edition.
 Resistance is a Global Problem

 Urgent global action is needed ?

7 Central Intelligence Agency. The global infectious disease threat and its implications for the United States. 1999
 WHO Efforts

 A global problem calls for a global response

World Health Organization Global Strategy: Raising

Awareness

Implementation of the WHO Global Strategy

8 World Health Assembly (fifty-first). Emerging and other communicable diseases: antimicrobial resistance. 1998
 Type of Drug Resistance

There are three types of drug resistance

1. Natural Resistance e.g. gram negative bacilli are normally

unaffected by penicillin G or Mycobacterium tuberculosis is insensitive to tetracycline

2. Acquired Resistance e.g Staphylococci, coliforms, tubercle bacilli

3. Cross Resistance e.g. resistance to one sulfonamide means

resistance to all derivative of sulfonamide

9 Gillespie SH. Evolution of drug resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother 2002, 46: 267–274
 Molecular Mechanism of Drug
Resistance
 Resistance may be developed by two types
1. Mutation- Microbes reproduce by dividing every few
hours allowing them to evolve rapidly and adapt
quickly to new environmental condition.

Spontaneous emergence of drug resistance

10 Tripathi KD. Essentials of Medical pharmacology, fifth Edition

 Molecular Mechanism of Drug
Resistance

2. Gene transfer- Microbes may also acquire genes

from each other, including genes that make
the microbe drug resistant.

Adapted emergence of drug resistance

11 Tripathi KD. Essentials of Medical pharmacology, fifth Edition

 Causes of antimicrobial drug
resistance

. Inadequate hospital infection control practices

. Use of expired drugs
. Poor storage conditions

12 Feinman SE. Antibiotics in animal feed: drug resistance re-visited. ASM News 1998, 64: 24-30.
 Drug Resistance: Major Issue

1. Drug resistance: HIV

2. Drug Resistance: Malaria
3. Drug resistsance: Tuberculosis
4. Methicillin-resistant Streptococcus aureus (MRSA)

13 WHO report on infectious diseases: Removing obstacles to healthy development 1999

 XDR-TB cases: WHO report 2009

14 http://www.who.int/topics/tuberculosis/en/
 HIV cases in TB patients

15 http://www.who.int/topics/tuberculosis/en/
 Future Research

1. Prevention of antimicrobial drug resistance4

2. Strategies for decreasing antimicrobial resistance4

3. Combination therapy4

4. Anti-TB Drug resistant model5

16 4. Moellering RC et al., update: Proceedings of an expert panel on resistance. Ameri J Infect Control, Vol 35, 2007, S1-S23
5. Gupta A et al., A model for high-throughput antituberculosis drug screening. J Antimicrob Chemother 2009, 64(4): 774-781
 THANK YOU

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