Antimicrobial Drug Resistance

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

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Antimicrobial; the “magic bullet”1

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Antibiotic: Compounds produced by micro-organisms and capable of inhibiting bacterial growth and bacterial infections1

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Antibacterials, like triclosan are also used in health concerning commercial products2

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 

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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.

Tripathi KD. Essentials of Medical pharmacology, fifth Edition.

Antimicrobial Drug Resistance

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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

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Several factors for emergence of drug resistance3 Misuse of antimicrobials Poor quality of available drugs 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

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http://www3.niaid.nih.gov/

Level of Resistance 

Resistance observed are three types

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First line drugs: Multiple Drug Resistance Second line drugs: Extremely Drug Resistance Third line drugs: Completely Drug Resistance

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To prevent the emergence of CDR Fourth line drugs: Under process

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Tripathi KD. Essentials of Medical pharmacology, fifth Edition.

Resistance is a Global Problem

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Urgent global action is needed ?

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

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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

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Gillespie SH. Evolution of drug resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother 2002, 46: 267–274

Molecular Mechanism of Drug Resistance  1.

Resistance may be developed by two types 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

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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

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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

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

Drug Resistance: Major Issue

1. 2. 3. 4.

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Drug resistance: HIV Drug Resistance: Malaria Drug resistsance: Tuberculosis Methicillin-resistant Streptococcus aureus (MRSA)

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

XDR-TB cases: WHO report 2009

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http://www.who.int/topics/tuberculosis/en/

HIV cases in TB patients

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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

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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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