Antimicrobial theraphy prepared by Miss Rashidah Hj Iberahim - PowerPoint Presentation

Slide1

Antimicrobial theraphy

prepared by Miss Rashidah Hj Iberahim

Slide2

Antimicrobial theraphy in daily life

prepared by Miss Rashidah Hj Iberahim

Slide3

Content

Overview of the mechanism of action of antimicrobial drugsAntimicrobial sensitivity test

Mechanism of antibiotic resistance

prepared by Miss Rashidah Hj Iberahim

Slide4

Introduction

Discovered by Paul Ehrlich (chemical killing pathogenic m/org

wtout injuring the host)

Antimicrobial

theraphy

Chemotheraphy

Antibiotic (antibiosis) – chemical (against life)

2 types synthetic

semisynthetic

prepared by Miss Rashidah Hj Iberahim

Slide5

prepared by Miss Rashidah Hj Iberahim

Slide6

General properties

Selective toxicityThe spectrum of activity

Modes of actionSide effectsResistance of m/org

prepared by Miss Rashidah Hj Iberahim

Slide7

PART 1 – GENERAL PROPERTIES

prepared by Miss Rashidah Hj Iberahim

Slide8

Selective toxicity

To way of actions

internal (eat)

external (topical)

Internal – should be selective toxicity (harm to microbes not the host cell)

Most of the antibiotic act depending on 2 levels

- toxic dosage level (cause host damage)

- therapeutic dosage level ( eliminates the pathogenic organism)

prepared by Miss Rashidah Hj Iberahim

Slide9

Relationship of antibiotic and host

Measured by chemotherapeutic index –

max dose

÷

min dose

= range 1 till 8

kg

bw

kg

bw

8 = > effective, < toxic1 = > toxic, < effectiveEg. arsenic, mercury, antimony = toxic and effective towards pathogenEg

. Treatment for worm infection = damage to parasites and host

prepared by Miss Rashidah Hj Iberahim

Slide10

The spectrum of activity

prepared by Miss Rashidah Hj Iberahim

Slide11

Modes of action

Inhibition of cell wall synthesis

Disruption of cell membrane function

Inhibition of protein synthesis

Inhibition of nucleic acid synthesis

Action as antimetabolites

prepared by Miss Rashidah Hj Iberahim

Slide12

1. Inhibition of cell wall synthesis

Normal mechanism, the peptidoglycan can helps to maintain the osmotic pressure of the cell

Allow the membrane of the effected microbe to rupture and release the cell content

Usually affecting

Gram positive bacteria

Examples – penicillin, bacitracin,

vancomycin

and cephalosporin

All the respective antibiotic contain

β

-lactam ring

that attach to enzyme and cross-link with peptidoglycan

However, those lack with peptidoglycan (Fungi and Archaea) were unaffected

prepared by Miss Rashidah Hj Iberahim

Slide13

2. Disruption of cell membrane function

Dissolve the membrane of interfere with the movement of substances into or out of the cells

Polypeptide antibiotic (

Polymyxins

)

act on bacteria as detergent and distort bacterial cell membranes by binding with the phospholipid bilayer

Effects on Gram negative bacteria (rich with phospholipids)

prepared by Miss Rashidah Hj Iberahim

Slide14

Cont.

Polyene antibiotic (amphotericin B)

Bind to particular sterols, present in the membranes of fungal and animal cellPolymyxins

– do not act on fungi

Polyenes

- do not act on bacteria

prepared by Miss Rashidah Hj Iberahim

Slide15

3. Inhibition of protein synthesis

Basically protein synthesis requires DNA, RNA and ribosomes (bacterial – 50S + 30S / animal – 60S + 40S)

Prevent the growth of microbes by disrupting ribosomes or otherwise, interfering with the process of translation

Thru selective toxicity (respective attack)

Examples:

S

treptomycin – from amino acids and

glycosidic

bonds that act on 30S portion interfering the translation process

Tetracycline

Erythromycin

, chloramphenicol – act on 50S portion and interfering the growing of polypeptide

prepared by Miss Rashidah Hj Iberahim

Slide16

4. Inhibition of nucleic acid synthesis

Interfere with the synthesis RNA (transcription) or DNA (replication) and disrupt the formation these molecules contain

The enzyme used by bacterial and animal cells to synthesize nucleic acids provide a means selective action of antimicrobial agents

Example:

rifamycin

family (transcription), quinolones (DNA replication) and metronidazole

Bind to a bacterial RNA polymerase and inhibit RNA synthesis

prepared by Miss Rashidah Hj Iberahim

Slide17

5. Action as antimetabolites

Affect normal metabolites by competitively inhibiting microbial enzymes or by being erroneously incorporated into important molecules such as nucleic acids

prepared by Miss Rashidah Hj Iberahim

Slide18

Side effects

Most of the host will show adverse effects such as toxicity, allergy and disruption of normal

microfloraMost of the antibiotic acts on pathogen, and also the normal floraLeads to

superinfections

will happens where the normal flora will demolished and no host defends in particular area

prepared by Miss Rashidah Hj Iberahim

Slide19

Resistance of m/org

Antibiotic resistance can be a result of 

horizontal gene transfer, and also of unlinked point mutations in the 

pathogen

 

genome

 and a rate of about 1 in 10

8

 per chromosomal replication.

The antibiotic action against the pathogen can be seen as an environmental pressure; those bacteria which have a mutation allowing them to survive will live on to reproduce.

They will then pass this trait to their offspring, which will result in a fully resistant colony.

prepared by Miss Rashidah Hj Iberahim

Slide20

prepared by Miss Rashidah Hj Iberahim

Slide21

The four main mechanisms:

Drug inactivation or modification: e.g. enzymatic deactivation of 

Penicillin

 G

 in some penicillin-resistant bacteria through the production of 

β-

lactamases

.

Alteration of target site: e.g. alteration of 

PBP

—the binding target site of penicillins—in 

MRSA

and other penicillin-resistant bacteria.

Alteration of metabolic pathway: e.g. some 

sulfonamide

-resistant bacteria do not require para-aminobenzoic acid (PABA), an important precursor for the synthesis of 

folic acid

 and 

nucleic acids

 in bacteria inhibited by sulfonamides. Instead, like mammalian cells, they turn to utilizing preformed folic acid.

Reduced drug accumulation: by decreasing drug 

permeability

 and/or increasing active 

efflux

(pumping out) of the drugs across the cell surface.

prepared by Miss Rashidah Hj Iberahim

Slide22

Diagram of resistance

prepared by Miss Rashidah Hj Iberahim

Slide23

History of resistance

The first antibiotic, penicillin, was discovered in 1929 by Sir Alexander Fleming, who observed inhibition of

Staphylococci on an agar plate contaminated by aPenicillium mold

prepared by Miss Rashidah Hj Iberahim

Slide24

In simple words..

Hereditary drug resistance (R) factors are carried by plasmids and transposons

Resistance may be due to enzymatic destruction of a drug, prevention of penetration of the drug to its target site, cellular or metabolic changes at target sites, or rapid efflux of the antibioticResistance can be minimized by the discrimination use of drugs in appropriate concentrations and dosages

prepared by Miss Rashidah Hj Iberahim

Slide25

Examples

Staphylococcus aureusPseudomonas aeruginosa

Streptococcus and EnterococcusClostridium difficile

Salmonella

 and 

E. Coli

Acinetobacter baumannii

prepared by Miss Rashidah Hj Iberahim

Slide26

PART 2 – DETERMINING MICROBIAL SENSITIVITY

prepared by Miss Rashidah Hj Iberahim

Slide27

The Disk Diffusion Method

Also known as Kirby-Bauer method

The sensitivity compared by size of inhibition zone around the disk referred to a table of standard measurements

prepared by Miss Rashidah Hj Iberahim

Slide28

The sensitivity level

prepared by Miss Rashidah Hj Iberahim

Slide29

2. The Dilution Method

Constant inoculum is placed into broth cultures or well

wt differing known quantities of chemotherapeutic agents

2 level of determination:

MIC

(minimum inhibitory concentration) - lowest concentration of growth / no growth at all

MBC

(minimum bactericidal concentration) – lowest cont. in which

subculturing

of broth yields no growth

prepared by Miss Rashidah Hj Iberahim

Slide30

prepared by Miss Rashidah Hj Iberahim

Slide31

3. Serum Killing Power

To determine the capability of antibiotic in killing the pathogen

By adding bacterial suspension to the patient’s serum that already taken the antibiotic for certain period of time

prepared by Miss Rashidah Hj Iberahim

Slide32

4. Automated Methods

prepared by Miss Rashidah Hj Iberahim

Slide33

Antibacterial agents

Refer to : slide on modes of action

prepared by Miss Rashidah Hj Iberahim

Slide34

Antifungal

Imidazoles and

TriazolesPolyenesGriseofulvin

Other agents

prepared by Miss Rashidah Hj Iberahim

Slide35

Antiviral agents

Purine and Pyrimidine AnalogsAmantadine

Interferons and Immunoenhancers

prepared by Miss Rashidah Hj Iberahim

Slide36

Antiprotozoan agents

Quinine

Chloroquine and PrimaquineMetronidazole

Other agents

prepared by Miss Rashidah Hj Iberahim

Slide37

Antihelminthic agents

Niclosamide

MebendazoleOther agents

prepared by Miss Rashidah Hj Iberahim

Slide38

Homeworks

Please study regarding each of the antimicrobial agents listed in this lecture.

Focus on the mechanism of actions, resistances and laboratory diagnostic.

prepared by Miss Rashidah Hj Iberahim

Slide39

The end

prepared by Miss Rashidah Hj Iberahim