ANTIMICROBIAL AGENTS

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ANTIMICROBIAL AGENTS
By
Dr. Emad AbdElhameed Morad
Lecturer of Medical Microbiology and Immunology
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Definitions

• Antibiotic substance of microbial origin with
  antimicrobial activity against other organisms.
• Chemotherapeutic agents synthetic drugs with
  antimicrobial activity.
• Bactericidal agents drugs which kill and
  destroy the bacteria.
• Bacteriostatic agents drugs which inhibit the
  growth and multiplication of bacteria without
  killing them.

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Ideal antimicrobial agent

• Selective toxicity harmful to the bacteria and
  non toxic to the host cells.
• Broad spectrum affect a variety of bacteria
  both Gram positive and Gram negative.
• Bactericidal better than bacteriostatic.
• Diffusible to distant body areas with slow rate
  of excretion.
• Bacteria do not develop resistance to it.

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Mechanisms of action of antimicrobial agents

• Inhibition of cell wall synthesis penicillin
  and cephalosporin.
• Inhibition of cell membrane function
  polymyxins, amphotericin-B, nystatin and
  colistin.
• Inhibition of protein synthesis
  chloramphenicol, tetracycline and aminoglycosides
  (amikacin and gentamicin).
• Inhibition of nucleic acid synthesis
• DNA inhibition by inhibiting DNA gyrase enzyme
  quinolones.
• RNA inhibition by inhibiting RNA polymerase
  enzyme rifampicin.
• Competitive inhibition sulphonamides compete
  with para-amino-benzoic acid (PABA) for the
  active site of the enzyme involved in folic acid
  synthesis.

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Choice of antimicrobial agent

• Choice of the antimicrobial agent depends on

In-vitro tests of bacterial sensitivity to
antibiotics
Empirical use of antibiotics
OR
Using antibiotics without in-vitro tests
Disc diffusion method
Dilution method
Closed lesions with no available sample such as
brain abscess
While waiting for the in-vitro sensitivity result
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Disc diffusion method

• Culture medium is inoculated with the organism.
• Discs impregnated with different antibiotics are
  placed on the medium.
• The plate is incubated at 37 degree for 24
  hours.
• The bacterial sensitivity to different
  antibiotics is determined by measuring the
  diameter of the zone of inhibition around each
  antibiotic disc.

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Steps of disc diffusion method
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Tube dilution method

• Serial dilutions of the antibiotic are
  inoculated with the organism to determine the
  minimal inhibitory concentration (MIC).
• MIC is the lowest concentration of the
  antibiotic that inhibits the bacterial growth.

Recently, MIC could be determined by 1- E test
(rectangular strip containing gradually
increasing concentration of the antibiotic) 2-
Automated system
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Tube dilution method
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E test
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Antimicrobial drug combination

• In severe infections.
• To avoid development of resistant strains.
• Synergism the combined effect of a pair of
  antimicrobial agents is greater than the sum of
  the two drugs acting separately such as use of
  penicillin and gentamicin (11gt2).

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Complications of antimicrobial agents

• Drug toxicity
• Chloramphenicol cause bone marrow inhibition.
• Aminoglycosides are nephrotoxic.
• Streptomycin is ototoxic.
• Tetracycline causes teeth deformity and liver
  damage.
• Hypersensitivity
• Some antimicrobials act as haptens.
• When they bind to host tissue proteins, they
  become antigenic and stimulate exaggerated immune
  response leading to tissue damage.

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• Superinfection
• During treatment with a broad spectrum
  antibiotic, susceptible members of normal flora
  at different body sites are killed.
• This will result in biological imbalance.
• Bacteria resistant to the antibiotic used will
  cause superinfection
• Candida may cause oral thrush.
• Clostridium defficile and staphylococci cause
  enterocolitis.
• Development of drug resistance
• The emergence of resistant mutants is encouraged
  by
• Abuse of antibiotics without in-vitro sensitivity
  testing.
• Inadequate dosage or duration of chemotherapy.

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Mechanisms of antimicrobial resistance

• Bacteria produce enzymes that inactivate the
  drug.
• Beta-lactamase enzymes cleaves the ß-lactam ring
  in penicillins and cephalosporins.
• Bacteria decrease their permeability to the
  drug.
• Streptococci resist aminoglycosides by this
  mechanism.
• Bacteria alter the target site for drug action.
• Resistance to aminoglycosides is associated with
  alteration in 30S subunit of the bacterial
  ribosome.

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• Development of alternative pathway to bypass the
  pathway inhibited by the drug.
• Bacteria resistant to sulphonamides utilize the
  folic acid with no need for PABA.
• Bacteria actively pump the drug out using efflux
  pump.

• Note that
• Genes mediating resistance of bacteria to
  antibiotics are frequently carried on plasmids.
• Plasmids could be transmitted between bacterial
  cells by three methods spreading the resistance
  between bacteria
• Transformation uptake of free DNA liberated
  from lysed bacterial cells.
• Conjugation transfer is mediated through sex
  pilus.
• Transduction transfer is done by
  bacteriophages.

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