antibiotic mode of action
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Antibiotics
•Definition
•Mode of action
•Examples
Dr.Sami Albaba
MSC.Muhammad Hashem
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A substance of biological, synthetic origin of
low molecular weight.
produced by a fungus or bacterium assecondary metabolites that inhibits or stop
growth of other microorganisms in vitro and
in vivo selectively, when it used in low
concentration.
Definition of Antibiotic
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Characteristics of Antibiotics
•It must be able to
reach the part of
the human bodywhere the
infection is
occurring.
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•It should not
cause the
development of resistant forms
of parasites.
Characteristics of Antibiotics
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Characteristics of Antibiotics
•It should not
produce undesirable
side effects in the
host such as allergic
reaction, nerve
damage or irritation
of the kidneys andgastrointestinal
tract.
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Antibiotic Therapy
•
Before giving any Antibiotics to patient youshould know:
•Identify infecting organism
•Evaluate drug sensitivity•Target site of infection
•Drug safety/side effect profile
•Patient factors
•Cost
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Classification of Antibiotics
•Bacteriostatic •Bactericidal
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Classification of Antibiotics
•Chemical Structure
•Spectrum of Activity
•Mechanism of Action
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Mechanism of Action
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Inhibitors of Cell Wall Synthesis
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Protein Synthesis Inhibitors
•Human Ribosome
–80S
–40S
–60S
•Bacterial Ribosome
–70S
–30S
–50S
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Inhibitors of Metabolism
•Sulfonamides
•Trimethoprim
•Interfere with the
production of folic acid
coenzymes that are
required for purine and
pyrimidine synthesis
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Major groups of Antibiotics
.1Beta-lactam antibiotics
1. Penicillins
2. Cephalosporins
3. Carbapenems
4. Monobactams
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1. Beta-lactam antibiotics Toxicity
Problem•The main toxicity problem
with these antibiotics is an
allergic reaction that occursbecause of formation of
beta-lactam/serum protein
conjugate that elicits aninflammatory immune
response.
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1. Beta-lactam antibiotics
Mode of Action
•The beta-lactam antibiotics
inhibit the last step inpeptidoglycan synthesis
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1. Beta-lactam antibiotics Spectrum
•Some are effectiveagainst both Gram-
positive and Gram-negative bacteria
whereas others aremore effective against
Gram-positive thanGram-negative
bacteria or vice versa.
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1. Beta-lactam antibiotics Example 1.
( Natural penicillins and cephalosporins )
• Penicillin G, Cephalothin
• Biological source
•
Penicillium notatum • Cephalosporium species
• Spectrum (effective against)
• Gram-positive bacteria
•Mode of action
• Inhibits steps in cell wall (peptidoglycan) synthesis.
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1. Beta-lactam antibiotics Example 2.
( Semisynthetic penicillin)
• Ampicillin, Amoxycillin
• Spectrum (effective against)• Gram-positive and Gram-negative bacteria
• Mode of action
• Inhibits steps in cell wall (peptidoglycan)
synthesis.
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1. Beta-lactam antibiotics Example 3.
(Clavulanic Acid )
• Clavamox(Aug) is clavulanic acid plus amoxycillin
• Biological source
• Streptomyces clavuligerus • Spectrum (effective against)
• Gram-positive and Gram-negative bacteria
•
Mode of action• Suicide inhibitor of beta-lactamases
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1. Beta-lactam antibiotics Example 5.
( Carbapenems, Carboxypenems )
• Imipenem: most broad-spectrum antibacterial drug.
• Biological source
• Streptomyces cattleya
• Spectrum (effective against)
• Gram-positive and Gram-negative bacteria, and ESBL
• Mode of action
• Inhibits steps in cell wall (peptidoglycan) synthesis.• Cost: Expensive (example:Tenam)
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Example 4. (Monobactams )
• Aztreonam: only monobactam available structure.
• Biological source
• Chromobacter violaceum
• Spectrum (effective against)
• Gram-positive and Gram-negative bacteria
• Mode of action
• Inhibits steps in cell wall (peptidoglycan) synthesisand murein assembly.
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First generation Cephalosporins
Agent: cefazolin, cephalexin, cefadroxil, cephalothin
Good for gram positive, moderate for some enteric gramnegative, and poor for enterococci.
Second generation Cephalosporins
Agent: Cefuroxime, cefdinir, cefotetan, cefaclor, cefoxitin
Good for some enteric gram negative, modertae for gram
positive, and poor for enterococci.
Third generation Cephalosporins
Agent: Ceftriaxone, cefotaxime, ceftazidime, cefpodoxime,cefixime.
Good for gram positive & negative, poor for MSSA, and
poor for enterococci and MRSA.
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Fourth generation Cephalosporins
Agent: cefepime.
Good for MSSA, gram positive & gram negative,moderate for Acinetobacter, and poor for
enterococci & MRSA.
inhibitor Lactamase-Beta
Agent: Ampicillin/sulbactam,
Amoxicillin/clavulanate, Ticarcillin/clavulanate,
Piperacillin/tazobactam.
Good for gram positive & negative, enterococci, and beta-
lactamase except ESBL(Extended Spectrum Beta
Lactamase) in this case we use only Carbapenems.
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2. Glycopeptides
•Another group of peptidoglycan
synthesis inhibitors is the
glycopeptides, exemplified byvancomycin and teichoplanin.
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2. Glycopeptides
• Vancomycin
• Biological source
• Streptomyces orientales
• Spectrum (effective against)
• Gram-positive bacteria, especially Staphylococcusaureus, MSSA, MRSA, enterococci, and poor for gram negative.
• Mode of action
• Inhibits steps in murein (peptidoglycan) biosynthesis
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3. Aminoglycosides
•Members of this group contain
sugars and consists of streptomycin,
dihydrostreptomycin, neomycin,gentamicin, kanamycin, tobramycin
and amikacin.
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3. Aminoglycosides
• Example 1.• Gentamicin
• Biological source
•
Micromonospora species• Spectrum (effective against)
• Gram-positive and Gram-negative bacteria esp.Pseudomonas, poor for anaerobes.
•
Mode of action• Inhibit translation (protein synthesis)
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3. Aminoglycosides
• Example 2
• Streptomycin
• Biological source
• Streptomyces griseus
• Spectrum (effective against)
• Gram-positive and Gram-negative bacteria
• Mode of action
• Inhibit translation (protein synthesis)
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4. Tetracyclines
•Tetracyclines consist of eight
members, and may be considered as
a group of antibiotics, obtained asbyproducts from the metabolism of
various species of Streptomyces .
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4. Tetracyclines
• Example 1.( Natural )
• Tetracycline (Bacteriostatic)
• Biological source
•Streptomyces species
• Spectrum (effective against)
• Gram-positive and Gram-negative bacteria,Rickettsias, enterococci, VRE, MRSA, poor for
pseudomonas, and proteus.• Mode of action
• Inhibit translation (protein synthesis)
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4. Tetracyclines
• Example 2. (Semisynthetic tetracycline)
Doxycycline
• Spectrum (effective against)
• Gram-positive and Gram-negative bacteria,Rickettsias , Borellia
• Mode of action
• Inhibit translation (protein synthesis)
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5. Macrolides
•Macrolides are an ill-defined group
representing those antibiotics that
have large ring structures containingoxygen.
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5. Macrolides
• Example
• Erythromycin
• Biological source
•Streptomyces erythreus
• Spectrum (effective against)
• H.influenza, Moraxella, H.pylori, Mycobacterium,streptococcus, poor for staph,and enteric gram
negtaive.• Mode of action
• Inhibits translation (protein synthesis)
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6. Lincosamides
•Lincosamides are a family of
antibiotics that bind to bacterial 50S
ribosomal subunit. They differconsiderably from macrolides in
structure.
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6. Lincosamides
• Example
• Clindamycin
• Biological source
•Streptomyces lincolnensis
• Spectrum (effective against)
• Gram-positive and anaerobes Gram-negativebacteria.
• Mode of action
• Inhibits translation (protein synthesis)
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7. Fluoroquinolones•Floroquinolones are a family of antibiotics that
interferes with DNA replication. Floroquinolones are
bactericidal antibiotics.
Nalidixic acid
Ciprofloxacin
Norfloxacin
Levofloxacin
Ofloxacin
Good for enteric gram negative, poor for Staph &
S.pneumoniae.
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8. Rifampin
•Rifampin (or Rifampicin) is an
antibiotic that inhibits bacterial RNA
polymerase by binding to itsß-subunit. Rifampin is a bactericidal
antibiotic.
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9. Polypeptides
• Example 1
• Polymyxin
• Biological source
• Bacillus polymyxa
• Spectrum (effective against)
• Gram-negative bacteria
• Mode of action
• Damages cytoplasmic membranes
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9. Polypeptides
• Example 2
• Bacitracin
• Biological source
•Bacillus subtilis
• Spectrum (effective against)
• Gram-positive bacteria
• Mode of action
• Inhibits steps in murein (peptidoglycan)biosynthesis.
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10. Polyenes
• Example 1.
• Amphotericin
• Biological source
• Streptomyces nodosus
• Spectrum (effective against)
• Fungi
• Mode of action
• Inactivate membranes containing sterols
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10. Polyenes
• Example 2.
• Nystatin
• Biological source
• Streptomyces noursei
• Spectrum (effective against)
• Fungi (Candida)
• Mode of action
• Inactivate membranes containing sterols
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11. Rifamycins
• Examples• Rifampicin
• Biological source
• Streptomyces mediterranei
• Spectrum (effective against)
• Gram-positive and Gram-negative bacteria,Mycobacterium tuberculosis
• Mode of action
• Inhibits transcription (eubacterial RNA polymerase)
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12. Phenols
• Example
• Chloramphenicol (Bacteriostatic)
• Biological source
• Streptomyces venezuelae
• Spectrum (effective against)
• Gram-positive and Gram-negative bacteria
• Mode of action
• Inhibits translation (protein synthesis)
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13. Nitrofurans
Agent: Nitrofurantoin
)Klebsiella(E.coli &UTIEspecial treatment for
Poor for Pseudomonas, Proteus, and some group
of gram positive.
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Clinical Microbiology
•Gram Positive Cocci
•Gram Positive Bacilli
•Gram Negative Cocci
•Gram Negative Bacilli
•Anaerobes
•Spirochetes
•Mycobacteria
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