antibiotic mode of action

7/29/2019 antibiotic mode of action

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Antibiotics

•Definition

•Mode of action

•Examples

Dr.Sami Albaba

MSC.Muhammad Hashem



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



Characteristics of Antibiotics

•It must be able to

reach the part of

the human bodywhere the

infection is

occurring.



•It should not

cause the

development of resistant forms

of parasites.





•It should not

produce undesirable

side effects in the

host such as allergic

reaction, nerve

damage or irritation

of the kidneys andgastrointestinal

tract.



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



Classification of Antibiotics

•Bacteriostatic •Bactericidal



Classification of Antibiotics

•Chemical Structure

•Spectrum of Activity

•Mechanism of Action



Mechanism of Action



Inhibitors of Cell Wall Synthesis



Protein Synthesis Inhibitors

•Human Ribosome

–80S

–40S

–60S

•Bacterial Ribosome

–70S

–30S

–50S



Inhibitors of Metabolism

•Sulfonamides

•Trimethoprim

•Interfere with the

production of folic acid

coenzymes that are

required for purine and

pyrimidine synthesis



Major groups of Antibiotics

.1Beta-lactam antibiotics

1. Penicillins

2. Cephalosporins

3. Carbapenems

4. Monobactams



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.



1. Beta-lactam antibiotics

Mode of Action

•The beta-lactam antibiotics

inhibit the last step inpeptidoglycan synthesis



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.



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.




( Semisynthetic penicillin)

• Ampicillin, Amoxycillin

• Spectrum (effective against)• Gram-positive and Gram-negative bacteria

• Mode of action

• Inhibits steps in cell wall (peptidoglycan)

synthesis.




(Clavulanic Acid )

• Clavamox(Aug) is clavulanic acid plus amoxycillin


• Streptomyces clavuligerus • Spectrum (effective against)

• Gram-positive and Gram-negative bacteria

•

Mode of action• Suicide inhibitor of beta-lactamases




( Carbapenems, Carboxypenems )

• Imipenem: most broad-spectrum antibacterial drug.


• Streptomyces cattleya


• Gram-positive and Gram-negative bacteria, and ESBL

• Mode of action

• Inhibits steps in cell wall (peptidoglycan) synthesis.• Cost: Expensive (example:Tenam)



Example 4. (Monobactams )

• Aztreonam: only monobactam available structure.


• Chromobacter violaceum



• Mode of action

• Inhibits steps in cell wall (peptidoglycan) synthesisand murein assembly.



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.



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.



2. Glycopeptides

•Another group of peptidoglycan

synthesis inhibitors is the

glycopeptides, exemplified byvancomycin and teichoplanin.



2. Glycopeptides

• Vancomycin


• Streptomyces orientales


• Gram-positive bacteria, especially Staphylococcusaureus, MSSA, MRSA, enterococci, and poor for gram negative.

• Mode of action

• Inhibits steps in murein (peptidoglycan) biosynthesis



3. Aminoglycosides

•Members of this group contain

sugars and consists of streptomycin,

dihydrostreptomycin, neomycin,gentamicin, kanamycin, tobramycin

and amikacin.



3. Aminoglycosides

• Example 1.• Gentamicin


•

Micromonospora species• Spectrum (effective against)

• Gram-positive and Gram-negative bacteria esp.Pseudomonas, poor for anaerobes.

•

Mode of action• Inhibit translation (protein synthesis)



3. Aminoglycosides

• Example 2

• Streptomycin


• Streptomyces griseus



• Mode of action

• Inhibit translation (protein synthesis)



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 .



4. Tetracyclines

• Example 1.( Natural )

• Tetracycline (Bacteriostatic)


•Streptomyces species


• Gram-positive and Gram-negative bacteria,Rickettsias, enterococci, VRE, MRSA, poor for

pseudomonas, and proteus.• Mode of action




4. Tetracyclines

• Example 2. (Semisynthetic tetracycline)

Doxycycline


• Gram-positive and Gram-negative bacteria,Rickettsias , Borellia

• Mode of action




5. Macrolides

•Macrolides are an ill-defined group

representing those antibiotics that

have large ring structures containingoxygen.



5. Macrolides

• Example

• Erythromycin


•Streptomyces erythreus


• H.influenza, Moraxella, H.pylori, Mycobacterium,streptococcus, poor for staph,and enteric gram

negtaive.• Mode of action

• Inhibits translation (protein synthesis)



6. Lincosamides

•Lincosamides are a family of

antibiotics that bind to bacterial 50S

ribosomal subunit. They differconsiderably from macrolides in

structure.



6. Lincosamides

• Example

• Clindamycin


•Streptomyces lincolnensis


• Gram-positive and anaerobes Gram-negativebacteria.

• Mode of action




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.



8. Rifampin

•Rifampin (or Rifampicin) is an

antibiotic that inhibits bacterial RNA

polymerase by binding to itsß-subunit. Rifampin is a bactericidal

antibiotic.



9. Polypeptides

• Example 1

• Polymyxin


• Bacillus polymyxa


• Gram-negative bacteria

• Mode of action

• Damages cytoplasmic membranes



9. Polypeptides

• Example 2

• Bacitracin


•Bacillus subtilis


• Gram-positive bacteria

• Mode of action

• Inhibits steps in murein (peptidoglycan)biosynthesis.



10. Polyenes

• Example 1.

• Amphotericin


• Streptomyces nodosus


• Fungi

• Mode of action

• Inactivate membranes containing sterols



10. Polyenes

• Example 2.

• Nystatin


• Streptomyces noursei


• Fungi (Candida)

• Mode of action

• Inactivate membranes containing sterols



11. Rifamycins

• Examples• Rifampicin


• Streptomyces mediterranei


• Gram-positive and Gram-negative bacteria,Mycobacterium tuberculosis

• Mode of action

• Inhibits transcription (eubacterial RNA polymerase)



12. Phenols

• Example

• Chloramphenicol (Bacteriostatic)


• Streptomyces venezuelae



• Mode of action




13. Nitrofurans

Agent: Nitrofurantoin

)Klebsiella(E.coli &UTIEspecial treatment for

Poor for Pseudomonas, Proteus, and some group

of gram positive.



Clinical Microbiology

•Gram Positive Cocci

•Gram Positive Bacilli

•Gram Negative Cocci

•Gram Negative Bacilli

•Anaerobes

•Spirochetes

•Mycobacteria

antibiotic mode of action

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