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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: [email protected] 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 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 The beta-lactam antibiotics inhibit the last step in peptidoglycan synthesis 1. Beta-lactam antibiotics Spectrum Some are effective against both Grampositive and Gramnegative bacteria whereas others are more effective against Grampositive than Gramnegative 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. 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 ) 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 ) 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 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 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 Ciprofloxacin Norfloxacin Ofloxacin 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 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) 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 Resistance to Antibiotics Resistance to Antibiotics Resistance to Antibiotics Resistance to Antibiotics Antibiotics Susceptibility Tests