Category: Entertainment

Presentation Description

No description available.


Presentation Transcript

PowerPoint Presentation:

Fading Miracle? Dr. Ashish J Post Graduate Dept of Microbiology Navodaya Medical College , Antibiotics in Microbiology

Structure of Lecture:

Structure of Lecture History of antibiotics Classification Principles of antibiotic treatment Mode of actions of antibiotics Resistance to antibiotics


Antibiotic/Antimicrobial Antibiotic : Chemical produced by a microorganism that kills or inhibits the growth of another microorganism Antimicrobial agent : Chemical that kills or inhibits the growth of microorganisms


Chemotherapy The use of drugs to treat a disease Selective toxicity : A drug that kills harmful microbes without damaging the host


History 19th century: – Louis Pasteur & Robert Koch: Bacteria as causative agents &recognized need to control them

Plant extracts:

Plant extracts Santonin (from Artemisia maritima, →against Ascaris, threadworm (helminths) →toxicity: disturbances of vision Quinine (from bark of Cinchona tree) →against malaria (protozoon) → “cinchonism” (impaired hearing, confusion) Ipecacuanha root →(emetic used e.g. in dysentery)

Toxic metals:

Toxic metals • Mercury →against syphilis (bacterial) • Arsenic TOO TOXIC ! (blindness) Ehrlich: testing of several modified derivatives for antimicrobial activity: no. 606 compound to test = - Trypanosoma and syphilis

PowerPoint Presentation:

Dyes • Paul Ehrlich : – noticed that parasites could be distinguished from host tissue by dyes – Trypan Blue (dead cells will be blue) - activity against Trypanosoma • Gerhard Domagk : – Prontosil (Sulphanilamide) - 1936 – azo-dye used in textile industry – 1st synthetic antibacterial in general

PowerPoint Presentation:

Paul Ehrlich • started science of chemotherapy • selective toxicity !! • systematic chemical modifications (“Magic Bullet”) • developed the Chemotherapeutic Index

Ehrlich’s Magic Bullets :

Ehrlich’s Magic Bullets

Fleming and Penicillin:

Fleming and Penicillin

PowerPoint Presentation:

Penicillin- the first antibiotic – 1928 Alexander Fleming observed the killing of staphylococci by a fungus ( Penicillium notatum ) • observed by others - never exploited

PowerPoint Presentation:

Selman Waksman - Streptomycin (1943) – active against all Gram-negatives – first antibiotic active against Mycobacterium tuberculosis

Microbial Sources of Antibiotics:

Microbial Sources of Antibiotics

Antibiotic Spectrum of Activity:

Antibiotic Spectrum of Activity

PowerPoint Presentation:

Types of antibiotic therapy • Targeted – based on sensitivity tests • Empiric – based on the symptoms and habits – knowledge of local epidemiological data • Prophylactic – e.g. intestinal operation

Possible side effects :

Possible side effects • Allergy – penicillins ! – type I hypersensitivity reaction ( anaphylaxy ) • Toxic effect – kidney, liver (alcoholism!), bone marrow – hearing – bones, teeth • Disbacteriosis = killing of the normal flora



Mechanisms of Antimicrobial Action:

Mechanisms of Antimicrobial Action Bacteria have their own enzymes for Cell wall formation Cell membrane function Protein synthesis DNA replication RNA synthesis Synthesis of essential metabolites

Mechanisms of Antimicrobial Action:

Mechanisms of Antimicrobial Action The more similar the pathogen and host enzymes, the more side effects the antimicrobials will have

Modes of Antimicrobial Action:

Modes of Antimicrobial Action

Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis:

Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis 1] Beta Lactam anti microbial agents Penicillin (over 50 compounds) Share 4-sided ring ( b lactam ring) Inhibits transpeptidation of peptidoglycan layer by binding with pencillin binding proteins. Broad spectrum Natural penicillins Narrow range of action Susceptible to penicillinase ( b lactamase)

Prokaryotic Cell Walls:

Prokaryotic Cell Walls

Penicillins Fig 20.6:

Penicillins Fig 20.6 Figure 20.6

Penicillinase (b Lactamase):

Penicillinase ( b Lactamase) Figure 20.8

Other Inhibitors of Cell Wall Synthesis:

Other Inhibitors of Cell Wall Synthesis Cephalosporins 2 nd , 3 rd , and 4 th generations more effective against gram-negatives Stable to staphylococcal penicillinases. Lack of activity against enterococci. Figure 20.9

PowerPoint Presentation:

Penicilinase-resistant penicillins Carbapenems: very broad spectrum Monobactam: Gram negative Oxa-cephems: eg Latamoxef Clavam Sulphones

Other Inhibitors of Cell Wall Synthesis:

Other Inhibitors of Cell Wall Synthesis Polypeptide antibiotics Bacitracin Topical application Against gram-positives Vancomycin Glycopeptide Important "last line" against antibiotic resistant S. aureus

Other Inhibitors of Cell Wall Synthesis:

Other Inhibitors of Cell Wall Synthesis Antibiotics effective against Mycobacteria: interfere with mycolic acid synthesis or incorporation Isoniazid (INH) Ethambutol

Inhibitors of Cell Membrane Function:

Inhibitors of Cell Membrane Function Daptomycin Binds and disrupts cell membrane of gram positive bacteria. Potent against MRSA,VRSA,VRE. Polymyxin Older agents that disrupts. Not equally effective against all microorganism

Inhibitors of Protein Synthesis:

Inhibitors of Protein Synthesis Broad spectrum, toxicity problems Examples Chloramphenicol Inhibits the addition of new amino acid to growing peptide chain by binding to 50 s ribosomal subunit wide spectrum → dysbacteriosis !! today mainly for: typhus abdominalis, ampR Haem. influenzae(bone marrow) Aminoglycosides: Bactericidal Acts on 30S ribosomal subunit. Inhibit formation of ribosomal initiation complex and also cause misreading of messenger RNA Streptomycin, neomycin, gentamycin (hearing, kidneys)

PowerPoint Presentation:

Tetracyclines act on 30S ribosomal subunit, inhibiting the binding of aminoacil-tRNA very wide spectrum ( Rickettsias & Chlamydia; GI tract) Macrolides : Large macrocyclic ring substituted with some unusual sugars. Interferes with translocation of mRNA. Acts on 50s Erythromycin (gram +, used in children) Azithromycin

PowerPoint Presentation:

Lincosamides Streptogramins Fusidic acid

Inhibitors of Nucleic Acid Synthesis:

Inhibitors of Nucleic Acid Synthesis Rifamycin Inhibits RNA synthesis If polymerization started already Antituberculosis Quinolones and fluoroquinolones Nalidixic acid Inhibits DNA gyrase Urinary tract infections Newer FQ wider spectrum, better activity.

Competitive Inhibitors:

Competitive Inhibitors Sulfonamides (Sulfa drugs) Inhibit folic acid synthesis Broad spectrum Figure 5.7

PowerPoint Presentation:

Metronidazol • against anaerobes + some protozoa • breaks down DNA • activated in the host cells by reduction of the nitro group at low redox potential (anaerobes!)

PowerPoint Presentation:

Nitrofurantoin : Reduced metabolites acts on DNA in manner analogous Novobiocin : Acts on beta subunit of DNA gyrase.

Antibiotic Resistance:

Figure 20.20 Antibiotic Resistance

Antimicrobial Resistance:

Antimicrobial Resistance Relative or complete lack of effect of antimicrobial against a previously susceptible microbe. Successful bacterial resistance to antimicrobial action requires interruption or disturbance of one or more steps for effective antimicrobial action.


Classification Two types Environmental mediated antimicrobial Microorganism mediated antimicrobial resistance Intrinsic Acquired


Intrinsic Results from normal genetic, structural or physiologic state of microorganism. Inherited Predictable. Useful in knowing the intrinsic resistance profiles.


Acquired Altered cellular physiology. Unpredictable. Genetic mutation Acquisition of genes from other organisms by plasmid (conjugation) by phage (transduction) by transposon (mobile genetic elements) by transformation (naked DNS) Combination

Mechanisms of Antibiotic Resistance:

Mechanisms of Antibiotic Resistance Enzymatic destruction of drug Prevention of penetration of drug Alteration of drug's target site Circumvention of consequences of antimicrobial agents. Rapid ejection of the drug

Antibiotic Selection for Resistant Bacteria:

Antibiotic Selection for Resistant Bacteria

What Factors Promote Antimicrobial Resistance?:

What Factors Promote Antimicrobial Resistance? Emergence of new genes Spread of old genes to new host Mutation of old genes resulting in more potent resistance. Emergence of intrinsically related opportunistic bacteria


Drugs Beta-Lactam Antibiotics Enzymatic destruction: Different types of enzymes Mostly plasmid coded Inducible Altered target Decreased uptake

PowerPoint Presentation:

Glycopeptides: Altered target Target overproduction Aminoglycosides: Enzymatic modification Decreased uptake Altered target

PowerPoint Presentation:

Quinolones Altered target Changes in DNA gyrase subunit Decreased uptake Macrolides: Efflux Altered target

PowerPoint Presentation:

Multi-resistance Combination of different independent mechanisms of resistance. Eg P aeruginosa is a type of multi-resistant bacteria. It is resistant to β-lactams, including third-generation cephalosporins, quinolones, chloramphenicol, and cyclines. (natural resistance) -Methicillin-resistant strains have become resistant to most antibiotics and with a high frequency of high resistance. (acquired) Cross-resistance Antibiotics of the same family. -Cross-resistance between penicillins, more widely between all the β-lactams including cephalosporins.

Inappropriate Antimicrobial Use:

Inappropriate Antimicrobial Use Prescription not taken correctly Antibiotics for viral infections Antibiotics sold without medical supervision Spread of resistant microbes in hospitals due to lack of hygiene

Inappropriate Antimicrobial Use:

Inappropriate Antimicrobial Use Lack of quality control in manufacture or outdated antimicrobial Inadequate surveillance or defective susceptibility assays Poverty or war Use of antibiotics in foods

Consequences of Antimicrobial Resistance:

Consequences of Antimicrobial Resistance Infections resistant to available antibiotics Increased cost of treatment

Multi-Drug Resistant TB:

Multi-Drug Resistant TB

MRSA “mer-sah”:

MRSA “mer-sah” Methicillin-Resistant Staphylococcus aureus Most frequent nosocomial (hospital-acquired) pathogen Usually resistant to several other antibiotics

Vancomycin Resistant Enterococci:

Vancomycin Resistant Enterococci

Vancomycin Use:

Vancomycin Use

Proposals to Combat Antimicrobial Resistance:

Proposals to Combat Antimicrobial Resistance Speed development of new antibiotics Track resistance data nationwide Restrict antimicrobial use Direct observed dosing (TB)

Proposals to Combat Antimicrobial Resistance:

Proposals to Combat Antimicrobial Resistance Use more narrow spectrum antibiotics Use antimicrobial cocktails

The Future of Chemotherapeutic Agents:

The Future of Chemotherapeutic Agents Antimicrobial peptides Broad spectrum antibiotics from plants and animals Squalamine (sharks) Protegrin (pigs) Magainin (frogs)

The Future of Chemotherapeutic Agents:

The Future of Chemotherapeutic Agents Antisense agents Complementary DNA or peptide nucleic acids that binds to a pathogen's virulence gene(s) and prevents transcription


References Jawetz , Melnick and Adelberg’s Textbook of Medical Microbiology Greenwood textbook of Medical microbiology Bailey and Scot textbook of Diagnostic microbiology Koneman textbook of medical microbiology CLSI guideline on antimicrobial therapy Chakraborthy textbook of microbiology Ananth Narayan textbook of medical microbiology

PowerPoint Presentation:

Thank you

authorStream Live Help