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Antibiotics

Modern medicine is dependent on chemotherapeutic agents, chemical agents that are used to treat diseases. Chemotherapeutic agents destroy pathogenic microorganisms or inhibit their growth at concentrations low enough to avoid undesirable damage to the host. Most of these agents are antibiotics (anti: against, biotic: bios, life), microbial products or their derivatives that can kill susceptible microorganisms or inhibit their growth.

The first antibiotic penicillin was discovered and developed in 1896 by a 21-year-old French medical student named Ernest Duchnense, his work was forgotten, and the Scotish physician Alexander Flemming rediscovered penicillin. The discovery of penicillin stimulated the search for other antibiotics. Selman Waksman announced in 1944 that he had found new antibiotic, streptomycin, produced by the actinomycete Strptomyces griseus.

Antibiotics vary in their range of effectiveness. Many are narrow spectrum- that is they are effective only against limited variety of pathogens. Other is broad spectrum and attack many different kinds of pathogens.

Chemotherapeutic agents can be synthesized independent of microorganism or manufactured by chemical procedures independent of microbial activity. A number of most commonly employed antibiotics are natural- that is totally synthesized by one of a few bacteria or fungi.

Microbial Sources of Antibiotics
Microorganism	Antibiotic
Bacteria Streptomyces spp. Micromonospora spp. Bacillus spp.	� Amphotericin B, Chloramphenicol (synthetic also), Erythromycin, Kanamycin, Neomycin, Nystatin, Rifampin, Streptomycin, Tetracyclines, Vancomycin Gentamicin Bacitracin, Polymixins
Fungi Penicillium spp. Cephalosporium spp.	� Griseofulvin, Penicillin Cephalosporins

In contrast several chemotherapeutic agents are completely synthetic. Eg. Ampicillin, Carbenicillin, Cephalosporins, Ciprofloxacin, Rifampin, Streptomycin etc (all are broad spectrum) and Bacitracin, Clindamycin, Dapsone, Erythromycin, Gentamicin etc (all are narrow spectrum). An increasing number of antibiotics are semisynthetic. Semisynthetic antibiotics are natural antibiotics that have been chemically modified by the addition of extra chemical groups to make them less susceptible to inactivation by pathogens. Ampicillin, carbenicillin and methicillin are good examples.

Mechanism of Antibiotic Drug Action

Drug

Mechanism

Cell wall synthesis Inhibition
Penicillin, Ampicillin, Carbenicillin, Methicillin, Cephalosporins
Vancomycin

Bacitracin

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Inhibit transpeptidation enzymes involved in the cross linking of the polysaccharide chains of the bacterial cell wall peptidoglycan. Activate cell wall lytic enzymes.
Binds directly to the D-Alpha-D-Alpha terminus and inhibits transpeptidation.
Inhibit cell wall synthesis by interfering with action of lipid carrier that transports wall precursors across the plasma membrane.

Protein Synthesis Inhibition
Streptomycin, Gentamycin

Chloramphenicol

Tetracyclines

Erythromycin and Clindamycin

Fusidic acid

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Binds with the 30s subunit of the bacterial ribosome to inhibit protein synthesis and causes misreading of mRNA.
Binds to the 50s ribosomal subunit and blocks peptide bond formation through inhibition of peptidyl transferase.
Bind to the 30s ribosomal subunits and interfere with aminoacyl RNA binding.

Bind to the 50s ribosomal subunit and inhibit chain elongation.

Binds to EF-G and blocks translocation.

Nucleic Acid Synthesis Inhibiton
Ciprofloxacin and other quinoloes
Rifampin

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Inhibit bacterial DNA gyrase and thus interfere with DNA replication, transcription, and other activities involving DNA.
Blocks RNA synthesis by binding to and inhibiting the DNA dependent RNA polymerase.

Cell membrane Disruption
Polymixin B

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Binds to the plasma membrane and disrupts its structure and permeability properties.

Metabolic Antagonism
Sulfonamides

Trimethoprim
Dapsone
Isoniazid

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Inhibit folic acid synthesis by competition with p-aminobenzoic acid.
Blocks tetrahydrofolate synthesis through inhibition of the enzyme dihydrofolate reductase.
Intereferes with folic acid synthesis.
May disrupt pyridoxal or NAD metabolism and functioning. Inhibits the synthesis of the mycolic acid �cord factor�.

Factors influencing the Effectiveness of Drugs:

1. The drug must be able to reach the site of infection.
2. The pathogen must be susceptible to drugs.
3. The chemotherapeutic agent must exceed the pathogen�s MIC value if it is going be effective.