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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.
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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.
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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.
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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
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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
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Inhibition of cell wall
synthesis:
-Lactam containing antimicrobial:
Penicillin.
Ampicillin.
Amoxicillin.
Amoxicillin-clavulinic acid.
Cephalosporins:
1st generation (Cephalothin, Cephapirin, Cephazolin,
Cephalexin, Cephradine, and Cefadroxil).
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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.
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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)
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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
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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.
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Cephalosporins:
Same as penicillin in action.
Resistance:
Poor permeation of bacteria (No entry).
Lack or alteration of PBPs.
β-lactamase production.
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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
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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.
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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.
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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 .
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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-
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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.
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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).
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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.
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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.
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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.
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Chloramphenicol:
Resistant by production of Chloramphenicol acetyl transferase.
Side effects:
GIT upset.
Aplastic anaemia.
Gray fatal syndrome.
(Have no develop liver so.)
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Lincosamide (Lincomycin and
Clindamycin):
From S. licolnsis.
Very active against bacteroides and
other anaerobes.
Cause Pseudomembranous colitis.
Acid stable.
Cold not penetrate CSF.
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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.
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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.
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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
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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
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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
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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
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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.
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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.
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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
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