Antibiotics By Dr. Humodi A. Saeed Associate Prof. of Medical Microbiology College of Medical Lab. Science Sudan University of Science and Technology E mail address:

Definition of Antibiotic A substance of biological, semisyntheticor synthetic origin of low molecular weight (on-protein) produced by a fungus or bacterium as secondary metabolites that inhibits or stop growth of other microorganisms in vitro and in vivo selectively, when it used in low concentration

Characteristics of Antibiotics  It must be able to reach the part of the human body where the infection is occurring.

Characteristics of Antibiotics  It should not cause the development of resistant forms of parasites.

Characteristics of Antibiotics  It should not produce undesirable side effects in the host such as allergic reaction, nerve damage or irritation of the kidneys and gastrointestinal tract.

Characteristics of Antibiotics  It should be given orally without inactivation by stomach acid, or by injection (parenterally) without binding to the blood proteins.

Characteristics of Antibiotics  Finally, it should have a high level of solubility in the body fluids and be possible to achieve concentrations in the tissue or blood, which are sufficiently high to inhibit or kill the infectious agent.

Major groups of Antibiotics 1. Beta-lactam antibiotics 1. Penicillins 2. Cephalosporins 3. Carbapenems 4. Monobactams

1. Beta-lactam antibiotics Toxicity Problem 1. Beta-lactam antibiotics Toxicity Problem  The main toxicity problem with these antibiotics is an allergic reaction that occurs because of formation of beta-lactam/serum protein conjugate that elicits an inflammatory immune response.

1. Beta-lactam antibiotics Mode of Action 1. Beta-lactam antibiotics Mode of Action  The beta-lactam antibiotics inhibit the last step in peptidoglycan synthesis

1. Beta-lactam antibiotics Spectrum 1. Beta-lactam antibiotics Spectrum  Some are effective against both Gram- positive and Gram- negative bacteria whereas others are more effective against Gram- positive than Gram- negative bacteria or vice versa.

1. Beta-lactam antibiotics Example 1. ( Natural penicillins and cephalosporins ) 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.

1. Beta-lactam antibiotics Example 2. ( Semisynthetic penicillin) 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.

1. Beta-lactam antibiotics Example 3. (Clavulanic Acid ) 1. Beta-lactam antibiotics Example 3. (Clavulanic Acid )  Clavamox 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

Example 4. (Monobactams )  Aztreonam   Biological source  Chromobacter violaceum   Spectrum (effective against)  Gram-positive and Gram-negative bacteria   Mode of action  Inhibits steps in cell wall (peptidoglycan) synthesis and murein assembly

1. Beta-lactam antibiotics Example 5. ( Carboxypenems ) 1. Beta-lactam antibiotics Example 5. ( Carboxypenems )  Imipenem   Biological source  Streptomyces cattleya   Spectrum (effective against)  Gram-positive and Gram-negative bacteria   Mode of action  Inhibits steps in cell wall (peptidoglycan) synthesis.

2. Glycopeptides  Another group of peptidoglycan synthesis inhibitors is the glycopeptides, exemplified by vancomycin and teichoplanin.

2. Glycopeptides  Vancomycin   Biological source  Streptomyces orientales   Spectrum (effective against)   Gram-positive bacteria, esp. Staphylococcus aureus   Mode of action  Inhibits steps in murein (peptidoglycan) biosynthesis

3. Aminoglycosides  Members of this group contain sugars and consists of streptomycin, dihydrostreptomycin, neomycin, framycetin, gentamicin, kanamycin, paromycin, tobramycin and amikacin.

3. Aminoglycosides 3. Aminoglycosides  Example 1.  Gentamicin   Biological source  Micromonospora species   Spectrum (effective against)  Gram-positive and Gram-negative bacteria esp. Pseudomonas   Mode of action  Inhibit translation (protein synthesis)

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)

4. Tetracyclines  Tetracyclines consist of eight members, and may be considered as a group of antibiotics, obtained as byproducts from the metabolism of various species of Streptomyces.

4. Tetracyclines  Example 1.( Natural )  Tetracycline   Biological source  Streptomyces species   Spectrum (effective against)  Gram-positive and Gram-negative bacteria, Rickettsias   Mode of action  Inhibit translation (protein synthesis)

4. Tetracyclines  Example 2. (Semisynthetic tetracycline) Doxycycline Doxycycline   Spectrum (effective against)  Gram-positive and Gram-negative bacteria, Rickettsias Ehrlichia, Borellia   Mode of action  Inhibit translation (protein synthesis)

5. Macrolides  Macrolides are an ill-defined group representing those antibiotics that have large ring structures containing oxygen.

5. Macrolides  Example  Erythromycin   Biological source  Streptomyces erythreus   Spectrum (effective against)  Gram-positive bacteria, Gram-negative bacteria not enterics, Neisseria,Legionella, Mycoplasma   Mode of action  Inhibits translation (protein synthesis)

6. Lincosamides  Lincosamides are a family of antibiotics that bind to bacterial 50S ribosomal subunit. They differ considerably from macrolides in structure.

6. Lincosamides  Example  Clindamycin   Biological source  Streptomyces lincolnensis   Spectrum (effective against)  Gram-positive and Gram-negative bacteria esp. anaerobic Bacteroides   Mode of action  Inhibits translation (protein synthesis)

7. Quinolones  Quinolones are a family of antibiotics that interferes with DNA replication. Quinolones are bactericidal antibiotics. Nalidixic acid CiprofloxacinNorfloxacinOfloxacin

8. Rifampin  Rifampin (or Rifampicin) is an antibiotic that inhibits bacterial RNA polymerase by binding to its ß-subunit. Rifampin is a bactericidal antibiotic.

9. Polypeptides  Example 1  Polymyxin   Biological source  Bacillus polymyxa   Spectrum (effective against)  Gram-negative bacteria   Mode of action  Damages cytoplasmic membranes

9. Polypeptides  Example 2  Bacitracin   Biological source  Bacillus subtilis   Spectrum (effective against)  Gram-positive bacteria   Mode of action  Inhibits steps in murein (peptidoglycan) biosynthesis.

10. Polyenes  Example 1.  Amphotericin   Biological source  Streptomyces nodosus   Spectrum (effective against)  Fungi   Mode of action  Inactivate membranes containing sterols

10. Polyenes  Example 2.  Nystatin   Biological source  Streptomyces noursei   Spectrum (effective against)  Fungi (Candida)   Mode of action  Inactivate membranes containing sterols

. Rifamycins11  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)

12. Phenols  Example  Chloramphenicol   Biological source  Streptomyces venezuelae   Spectrum (effective against)  Gram-positive and Gram-negative bacteria   Mode of action  Inhibits translation (protein synthesis)

Resistance to Antibiotics

Antibiotics Susceptibility Tests