Chemotherapy antibiotics



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CHEMOTHERAPY


ANTIBIOTICS (DEFINITIONS)

  • Antibiotics (anti-against, bios-life) are the substances able to inhibit microorganisms.

  • Antibacterial agents are any compounds natural, synthetic, or semi-synthetic that are clinically useful in the treatment of bacterial infections.



ANTIBIOTICS

  • Bacteriostatic agents (sulfonamides, chloramphenicol) inhibit bacterial growth

  • Bacteriocidal agents (penicillin, streptomycin) significantly reduce the number of viable bacteria in the culture. Bactericidal agents generally kill only growing organisms



ANTIBIOTICS

  • Narrow spectrum antibacterial agents are preferentially active against other Gram + or Gram- bacteria

  • Broad-spectrum antibacterial agents are active against Gr+ and Gr- bacteria



THE ACTIVITY OF ANTIBIOTICS

  • The activity of antibiotics is expressed in international unit (IU). IU of penicillin (oxford unit) is the smallest amount of preparation inhibiting the growth of a standard S. aureus strain.

  • One unit of activity (A.U.) corresponds to the activity of 0.6 micrograms (mg) of the chemically pure crystalline sodium salt of benzylpenicillin.



Classification of antibacterial agents

  • 1. According to origin

  • Antibiotics produced by:

    • Fungi - Penicillins
    • Actinomycetes – Streptomycin, Erythromycin, Tetracycline
    • Bacteria - Gramicidins
  • Semisynthetic antibiotics: Ampicillin, Oxicillin

  • Sulfonamides

  • Derivatives of imidazoles: Metronidazole

  • Quinolones: Norfloxacin, Abactal, Ofloxacin

  • Derivative of pyrimidine: Trimethoprim

  • Derivatives of Arsenic (As), Bismuth (Bi), Mercury (Ar), Acridine.



Classification of antibacterial agents

  • 2. On the of chemical composition

  • Beta-lactams: Penicillins, Cephalosporins

  • Derivatives of dioxiaminophenilpropan: Levomycetin (Chloramphenicol)

  • Tetracyclines

  • Aminoglycosides: Gentamicin

  • Macrolides: Erythromycin

  • Acyclic antibiotics: Nistatin

  • Lincosamides: Lincomycin



Classification of antibacterial agents

  • A. Inhibitors cell wall synthesis

  • B-lactams (Penicillins, Cephalosporins)

  • Other inhibitors of bacterial cell wall synthesis: Cycloserine, Vancomycin, Bacitracin

  • B. Inhibitors nucleotide synthesis

  • Sulfonamides: Trimethoprim, Sulfa-methoxazole-trimethoprim.



Classification of antibacterial agents

  • C. Inhibitors nucleic acid synthesis

  • DNA synthesis inhibitors: Novobiocin, Quinolones, Nitroimidazoles (Metronidazole)

  • RNA synthesis inhibitors: Rifampin

  • D. Inhibitors protein synthesis

  • Inhibitors of the 30 s ribosomal unit: Aminoglycosides, Tetracyclines

  • Inhibitors of the 50 s ribosomal unit: Chloramphenicol, Macrolide (Erythromycin, Clarithromycin), Lincomycin



General principles of effective antibacterial therapy

  • The choice of antibacterial agent should be based on susceptibility

  • When the infection is life-threatening or when early treatment is extremely important, treatment is initiated with broad-spectrum antibiotics without detection susceptibility



General principles of effective antibacterial therapy

  • 3. Early treatment usually involves short-term therapy, which has the advantage of reducing the possibility of superinfection.

  • 4. Infections of poorly vascularized tissues (e.g. Endocarditis, Osteomyelitis) should be treated with bactericidal antibiotics.



Antibiotic susceptibility testing

  • Antibiotic susceptibility testing allows the choice of the best antibiotic with the narrowest spectrum and highest effectiveness against the isolated bacteria

    • Tube dilution test
    • The agar diffusion test (Bauer-Kirby test)
    • E-test method
    • Automated tests


Definition of MIC by Tube Dilution Test

  • Minimal inhibitory concentration (MIC) is the lowest concentration of an antibiotic that will inhibit the growth of a microorganism.



Interpretation of Tube Dilution Test

  • A bacterium is considered clinically susceptible to a given antibiotic if a blood level 2-4 times the MIC can be attained with the usual dosages and no appreciable side effects



Kirby - Bauer technique

  • Broth culture of an isolated bacterium is spread into an agar plate and paper disks impregnated with known concentration of different antibio-tics are dropped on the surface of the seeded plate



Antibiotic susceptibility testing plate

  • You should measure the diameter of zones of inhibition in millimeters. The zone seen here measures 20 mm in diameter



Interpretation of Disc Diffusion Test



E-test method

  • Applying the plastic strip impregnated with different concentrations of antibiotic onto the surface of the agar plate

  • Incubating plates. Plates should be read as early as possible after 24 hours incubation and results recorded in the susceptibility book.

  • Measure MIC of antibiotic as shown in Figure.



E-test method



Automated tests

  • These tests measure the inhibitory effect of the antimicrobial agents in a liquid medium by using light scattering to determine growth of the test organism. Results can be obtained within a few hours.



Bacterial Resistance

  • The two basic mechanisms of bacterial resistance

  • Mutation

  • Transfer of resistance genes through plasmids



MECHANISMS OF RESISTANCE TO ANTIBIOTICS

  • Intrinsic resistance

  • Alteration in the transport system, cell wall, or cell membrane

  • Enzymatic inactivation of the drug

  • Target alteration



Why has antibiotic resistance occurred?

  • Pressure on doctors, by patients, to prescribe antibiotics even when they are not needed.

  • Patients being prescribed antibiotics without the doctor knowing the cause of the infection.

  • Use of antibiotics in animals for growth promotion and prophylaxis, which allows them to enter the human food chain.



MECHANISMS OF RESISTANCE TO ANTIBIOTICS



MECHANISMS OF RESISTANCE TO ANTIBIOTICS



MECHANISMS OF RESISTANCE TO ANTIBIOTICS



MECHANISMS OF RESISTANCE TO ANTIBIOTICS



SIDE EFFECTS OF ANTIBIOTICS

  • 1. Organotoxic action: neurotoxic (Streptomycin); toxic action on the haematopoietic system (Tetracyclines).

  • 2. Allergic reactions: angioneurotic oedema, anaphylactic shock, allergic asthma, contact dermatitis (Penicillin).



SIDE EFFECTS OF ANTIBIOTICS

  • 3. Development of resistant strains of microorganisms which cause various complications

  • 4. Dysbacteriosis - disorders of normal flora of intestine and appears of infections.

  • 5. Immunosupression action.



INTERFERONS

  • Interferons - are natural substances that have anti-viral properties. Interferons are synthesized by cells infected an virus.

  • Type I

  • -Interferon-α (IFN-α) has maximal antiviral activity

  • -Interferon-β (IFN-β) has intermediate antiviral activity.

  • Mechanism of action IFN-α and IFN-β:

  • 1. Inhibit viral protein synthesis.

  • 2. May block other stages of viral replication, including budding.





INTERFERONS

  • Type II

  • -Interferon-α (IFN-α) is more active as a lymphokyne than as an antiviral agents.

  • Type III

  • Mechanism of action Interferon-γ (IFN γ)

  • 1. Inhibits viral replication by increasing intracellular nitric oxide levels;

  • 2. Activates cytotoxic T cells, monocytes, macrophages, and natural killer cells, which are able to kill virus-infected cells.

  • IFN-α is used in the treatment of Hepatitis B, C Herpes simplex virus, cytomegalovirus, AIDS - associated Kaposi’s sarcoma.

  • IFN-γ is used as an immunostimulant in the treatment of oncologic disorders and some immunodeficiency diseases.



Synthetic Antiviral Agents



Synthetic Antiviral Agents



Synthetic Antiviral Agents




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