Antimicrobial Chemotherapy. Antibiotics. Drug Resistance of Bacteria

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Antimicrobial Chemotherapy. Antibiotics. Drug
Resistance of Bacteria
Vinnitsa National Pirogov Memorial Medical
University / Department of microbiology
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Chemotherapy and chemotherapeutic agents

• Chemotherapy
• Chemotherapeutic agents
• Antibiotics
• Chemotherapeutic index

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Development of chemotherapy

• Paul Erlich found that dye Trypan Red was active
  against the trypanosome (causative agent of
  African sleeping sickness) in 1904
• In 1910 P. Erlich discovered the arsenical
  compounds and one of their was active against the
  syphilis spirochete (later was called Salvarsan)
• Cherhard Domagk discovered sulfonamides (red
  streptocide) that were effective for treatment of
  streptococci and staphylococci infections in 1935
  (Nobel Prize in 1939)
• In 1929 A.Fleming got penicillin, a first
  antibiotic
• In 1939 penicillin was produced and purified by
  chemists H.Flory and E.Chain (A.Fleming, H.Flory
  and E.Chain received the Nobel Prize in 1945)
• Selman Waksman announced in 1944 that he had
  found a new antibiotic streptomycin (he received
  Nobel Prize in 1952)

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Chemotherapeutic Index (CTI)

•  

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Classification of chemotherapeutic agents
according to target (general microbial group they
act against)

• Antimicrobial drugs
• Antiviral drugs
• Antifungal drugs
• Antiprotozoan drugs
• Antitumoral drugs

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Classification of chemotherapeutic agents

• Narrow-spectrum drugs
• Broad-spectrum drugs
• Specific-spectrum drugs (antituberculous,
  antiviral, etc.)

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Classification of chemotherapeutic agents

• Due to their total effect
• With cidal action
• With static action
• Due to their manufacture
• Natural
• Semi synthetic
• Synthetic

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Chemical classification of CTD

• Heavy metal derivates
• Sulfonamides
• Diaminopyrimidins
• Analogs of iso-nicotinic acid
• Nitrofuran derivatives
• Quinolones
• Chinoxalines
• Oxychinolones
• Azoles
• Metronidazole
• Alkaloid preparations
• Chinine derivate

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Antibiotics

• According to origin antibiotics are subdivided
  into next groups
  
• Antibiotics produced by fungi.
• Antibiotics produced by actinomycetes.
• Antibiotics produced by bacteria
• Plant antibiotics (phytoncides)
• Animal antibiotics (lysozyme, interferons)

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Mechanism of antibiotic action

• Cell wall synthesis inhibitors
• Protein synthesis inhibitors
• Cell membrane disruptors
• Nucleic acid synthesis inhibitors

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Antibiotic action onto bacterial cell
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Chemical antibiotics classification

• Penicillins
• Cephalosporins
• Carbapinems
• Monobactams
• Vancomycin
• Bacitracin
• Cycloserine
• Antitumoral antibiotics

• Aminoglycosides
• Tetracyclines
• Macrolides
• Chloramphenicol
• Linezolid
• Rifampin
• Polymyxin
• Polyenes

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Chemical structure of ß-lactams
Penicillin nucleus
Cephalosporin nucleus
Carbapenem nucleus
Monobactam nucleus
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B-lactams influence onto bacterial cell wall
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Chemical structure of gentamicin
Chemical structure of a tetracycline
Chemical structure of chloramphenicol
Chemical structure of lincomycin
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Action of aminoglycosides onto protein synthesis
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Determination of antimicrobial effectiveness of
chemotherapeutic agents

• Dilution susceptibility tests
• Disk diffusion tests
• E-tests
• Accelerated tests

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Broth dilution test
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Disk diffusion test
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Side effects of chemotherapy

• Allergic response
• Toxic effects
• Disbacteriosis
• Inhibition of immune system
• Embryotoxic action
• Formation of the drug resistance

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Resistance to antimicrobial drugs

• Natural
• Acquired (mutation and genetic recombination)

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