Medical laboratory sciences Basic microbiology (MLS-BMIC-224) … agents.pptx sara.2019.pdf · Antimicrobial agents SARA EL-SHEIKH MOHAMMED 0990997818 Medical laboratory sciences

Antimicrobial agents

SARA EL-SHEIKH MOHAMMED

0990997818

Medical laboratory sciences

Basic microbiology (MLS-BMIC-224)

Batch 9

1

Antimicrobial agents:

Chemical and therapeutic agents that acts against bacteria, viruses, fungi and parasite.

Antibiotic ------ Natural product from microorganism.

Chemotherapy ------ Chemically synthetic or semi synthetic agent.

2

Bactericidal: Killing effects

Bacteriostatic: Inhibition

Narrow spectrum: Narrow rang of

Microorganism.

Broad spectrum: Wide range of M.O

Minimum Inhibitory Concentration:

Lowest conc. Of antimicrobials that stop

the growth of M.O

Terminology 3

Minimum Bactericidal Concentration:Lowest concentration of antimicrobials

that kill M.O.

Synergism: The effects of 2 antimicrobials better than antimicrobial alone.

Antagonistic effects: Effects of 2 antimicrobial is less than antimicrobial alone.

4

What is an Antibiotic?

An antibiotic is a selective poison.

It has been chosen so that it will kill the desired

bacteria, but not the cells in your body. Each

different type of antibiotic affects different

bacteria in different ways.

5

History

In 1928, Sir Alexander Fleming, a Scottish

biologist, observed that Penicillium

notatum, a common mold, had destroyed

staphylococcus bacteria in culture

Clinical use of sulfonamide 1936

Penicillin was isolated in 1939

6

Sir Alexander FlemingPenicillium notatum

7

Classification accchemical structure and mechanism of

action

Inhibition of synthesis of bacterial cell wall

Acting directly on cell membrane, permeability,

leakage

Inhibition of protein synthesis

Inhibition of DNA gyrase, RNA polymerase

Inhibiton of folic acid metabolism

8

9

10

Inhibition of cell wall

synthesis:

-Lactam containing antimicrobial:

Penicillin.

Ampicillin.

Amoxicillin.

Amoxicillin-clavulinic acid.

Cephalosporins:

1st generation (Cephalothin, Cephapirin, Cephazolin,

Cephalexin, Cephradine, and Cefadroxil).

11

Cephalosporins:

2nd generation: (Cefoxitin, Cefotetan, Cefamandole,

Cefuroxime, Cefonicid, Cefaclor, Cefprozil,

Cefmetazole).

3rd generation: (Cefotaxime, Ceftizoxime, Ceftriaxone,

Ceftazidime, Cefoperazone, Cefixime, Ceftibuten).

4th generation: (Cefepim).

Bacitracin.

Vancomycin.

12

1. -Lactam containing Antibiotics

Penicillin: From Penicillium notatum. Active part is β-lactam ring. Inter through penicillin binding proteins. Resistant by:

Production of β-lactamase.Lack or alteration of PBPs.Failure in activation of autolytic enzyme.Failure in synthesis of peptidoglycan (Mycoplasma).

Side effect: Penicillin allergy.

Types: Penicillin G Acid sensitive (IV and IM).

Penicillin V Acid Resistant (Oral)

13

Ampicillin:

Broad spectrum antimicrobial

(G+ve and some G-ve).

Acid tolerant.

Amoxicillin:

Have wide range of activity against G+ve G-ve and some Anaerobe)

Could be taken orally.

Amoxicillin-Clavulinic acid (Augmentin or Amoclan):

More penicillinase resistant antimicrobial

14

Monobactam: IV or IM antimicrobial that active against

G-ve bacteria and resist β-lactamase

(e.g.: Aztreonam).

Carpebnems:Active against G+ve and G-ve bacteria and

anaerobes except bacteroides.

Could reach CSF.

Side effects:Skin rash, diarrhoea, vomiting, and

Hypersensitivity.

15

Cephalosporins:

Same as penicillin in action.

Resistance:

Poor permeation of bacteria (No entry).

Lack or alteration of PBPs.

β-lactamase production.

16

Cephalosporins:

Side effects:

Hypersensitivity.

Thrombocytopenia.

1st generation:

Active against G+ve cocci except enterococci, moderate

active against E.coli, Klebsiella, proteus and some anaerobic.

Cephalexin and Cephradin given orally.

Could be used in UTI and RTI.

Cephalexin used as post operative prophylaxis

17

2nd generation:

Active against G+ve and G-ve (except

pseudomonas) and some anaerobe.

3rd generation:

Less active against G+ve, but active against G-ve

and moderate action against pseudomonas.

Have the ability to reach the CSF.

4th generation:

Act against G-ve including Enterobacter and

Citrobacter Pseudomonas and moderate sensitive

against G+ve.

18

2. Bacitracin:

From B. subtilus.

Inhibit early cell wall synthesis in cell membrane (inhibit

lipid carrier).

Poor absorbance from GIT.

Very active against G+ve bacteria.

Used as ointment.

Side effect:

Kidney damage.

19

3. Vancomycin:

Bind with peptide chain inhibiting transpeptidation.

It is used I.V

It is given orally to treat pseudomembranous

colitis

Side effects:

Skin rash .

Kidney damage. Nephrotoxicity .

Ototoxicity .

20

Inhibition of cell membrane:

➢ Polymexin B and Colistin Disrupt plasma membrane structure.

Bacteriocidal for G-ve and G+ve.

High toxic used as Ointment.

Side effects:

Nephrotoxic.

Neurotoxic.

Daptomycin :Active against g+ but not g-

21

22

Inhibition of Protein synthesis:

Inhibition of 30 SrRNA:

Aminoglycoside.

Tetracyclins

Inhibition of 50 SrRNA:

Chloramphenicol.

Lincosamide ( Lincomycin and clindamycin).

Macrolides (Erythromycin and Clarithromycin).

Fusidic acid Affect Elongation factor G.

23

Aminoglycoside:

Streptomycin, Neomycin, Kanamycin,

Amikacin, Gentamicin, and tobramycin.

Bacteriostatic inhibit 30 S rRNA.

Active at alkaline PH.

Broad spectrum (G+ve and G-ve and

Mycobacterium).

24

AminoglycosideGive synergistic effect with penicillin.

In blood culture aminoglycoside inhibitedby Na polyantha sulfonate.

Resistance by:

Deficiency in Ribosomal receptor.

Lack of permeability to the drug(transportation is oxygen dependent).

Side effect:

Nephrotoxic and Ototoxic.

25

Doxycycline and

Tetracyclines:

Inhibit G+ve, G-ve, Rickettsia, Chlamydia,

Mycoplasma, Brucella, Yersinea and Vibreo.

Bacteriostatic in action.

Have poor penetration to CSF.

Side effects:

Gastrointestinal upset (Nausea, Vomiting, and Diarrhoea).

Skin rash.

Deposition in bone structures and teeth particularly in fetus.

26

Chloramphenicol:

From S. vensuelae (Now synthesized).

Wide distributed in all body fluid

including CSF.

Inactivated in liver and secreted in

urine in inactive form.

Bacteriostatic in action.

27

Chloramphenicol:

Resistant by production of Chloramphenicol acetyl transferase.

Side effects:

GIT upset.

Aplastic anaemia.

Gray fatal syndrome.

(Have no develop liver so.)

28

Lincosamide (Lincomycin and

Clindamycin):

From S. licolnsis.

Very active against bacteroides and

other anaerobes.

Cause Pseudomembranous colitis.

Acid stable.

Cold not penetrate CSF.

29

Macrolides (Erythromycin,

azithromycin and Clarythromycin):

From S. erythrus.

Resistance by alteration of rRNA receptor.

Active at alkaline PH.

Active at G+ve, G-ve, Chlamydia, Mycoplasma and Legionella.

Side effects:

GIT upset.

Fever.

Affect liver cells causing hepatitis.

30

Quinolones: Block DNA gyrase.

E.g.: Nalidixic acid, Oxolinic acid, Ciprofloxacin, Ofloxacin, Norfloxacin, Pefloxacin, and Nitrofurantoin.

Used in UTI.

Active against G-ve, G+ve, Haemophilus, Pseudomonas and Mycobacterium.

Side effect:

Nausea, headache, and dizziness.

Skin rash.

Impaired liver function.

Inhibition of Nucleic acid:31

Rifampin:

Active against some G+ve, G-ve, Enteric cocci, Mycobacterium, Chlamydia and pox virus.

Bind with RNA polymerase (inhibit RNA synthesis).

Could penetrate inside phagocytic cells.

Side effects:

Orange pigment in urine and sweat.

Skin rash.

Thrombocytopenia.

Impaired liver function.

32

Metabolic antagonistic:

Bacteriostatic for some G+ve and G-ve bacteria.

Inhibit folic acid synthesis.

Synergistic effect obtained from Cotrimoxazole

(Trimethoprim and Sulphomethoxazole).

Side effects:

Hypersensitivity.

Fever and skin rash.

GIT disturbances.

Depression of bone marrow.

Liver and kidney function abnormality.

Sulphonamide and trimethoprim:33

Susceptibility vs. Resistance

of microorganisms to Antimicrobial

Agents

Success of therapeutic outcome depends on:

Achieving concentration of ATB at the site of

infection that is sufficient to inhibit bacterial

growth.

Complete ATB-mediated killing is necessary

34

Susceptibility vs. Resistance

(cont.)

Dose of drug has to be sufficient to produce effect inhibit

or kill the microorganism:

However concentration of the drug must remain below

those that are toxic to human cells –

If can be achieved – microorganism susceptible to the ATB

If effective concentration is higher than toxic-

microorganism is resistant

35

Susceptibility vs. Resistance

(cont.)

Limitation of in vitro tests

In vitro sensitivity tests are based on

non-toxic plasma concentrations –

cut off

Do not reflect concentration at the

site of infection

36

Resistance

To be effective ATB must reach the

target and bind to it.

Resistance:

Failure to reach the target

The drug is inactivated

The target is altered

37

Resistance (cont.)

Bacteria produce enzymes at or within the cell surface

–inactivate drug

Bacteria possess impermeable cell membrane prevent

influx of drug.

Transport mechanism for certain drug is energy

dependent- not effective in anaerobic environment.

ATB as organic acids penetration is pH –dependent.

38

Resistance (cont.)

Acquired by mutation and passed vertically by selection to daughter

cells.

More commonly – horizontal transfer of resistance determinant from

donor cell, often another bacterial species, by transformation,

transduction, or conjugation.

Horizontal transfer can be rapidly disseminated

By clonal spread or resistant strain itself

Or genetic exchange between resistant and further susceptible strains.

39

40

Videos can help you

Mechanisms and Classification of Antibiotics

https://www.youtube.com/watch?v=NGwP471sehI

ß-Lactams: Mechanisms of Action and Resistance

https://www.youtube.com/watch?v=qBdYnRhdWcQ

Animation of Antimicrobial Resistance

https://www.youtube.com/watch?v=4oukHcpQoXM

Action Mechanism of Anti-biotics

https://www.youtube.com/watch?v=A8LOEZ3c1xc

Antibiotic resistance animation video

https://www.youtube.com/watch?v=mngVeKX8plk&pbjreload=10

41