Quartz 5

Resistant Bacteria

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Antibiotics (Etiotropic Agents)

Resistant Bacteria are selected when the dose of the Antibiotics is in the MSW Mutant Selection Window (Between MIC and MPC)
Here the dose is strong enough to kill sensitive bacteria, but to weak to kill Resistant Bacteria > Selection of the Resistant Bacteria

Resistance genes encoding:

  • Chromosomal: Frequently vertical transmission (through the bacterial clone growth)
  • Plasmid: Both vertical (clone growth) and horizontal (DNA exchange between two bacteria) transmission
    • ex: Colistin Resistance mcr-1 gene in Escherichia Coli and Salmonellae

Horizontal gene transmission:

  1. Conjugation: Sex fimbria of bacteria allow for direct plasmid DNA exchange between two bacteria
  2. Transduction: Indirect DNA exchange from a bacteria to multiple bacteria through a virus (Bacteriophage)
    1. The bacteriophage integrates parts of the donor bacteria’s DNA in its own genome when it replicates and injects it when it infects other bacteria
  3. Transformation: Minor significance, dead bacteria DNA is absorbed and integrated by neighbor bacteria

Resistance mechanisms:

  1. Antibiotics degrading enzyme:
    1. ex: β-Lactamase: degrading β-Lactams Antibiotics
      1. Most frequent resistance mechanism in Staphylococcus and Gr- bacteria
      2. ESBL Extended Spectrum β-Lactamase producing bacteria resist to all 4 generations of Cephalosporins (Resistant Bacteria)
        • The important ESBL enzymes are named (CTX-M, SHV, TEM)
        • Only Carbapenems and Monobactams (Last resort Antibiotics for Humans only) work against ESBL producing bacteria
  2. Antibiotics transforming enzymes:
    1. ex: Acetylation, Adenylation degrading Aminoglycosides
  3. Increasing integrity of the cell wall:
    1. Alteration of the Porin channels preventing Antibiotics entrance
  4. Increased efflux pump expression:
    1. Reduction of the Antibiotics IC concentration
  5. Modification of the binding sites:
    1. Enzymes / targets modifications: Antibiotics can’t act
      1. ex: Reduced binding of Fluoroquinolones to DNA topoisomerase
      2. ex: Mutated PBP enzymes in MRSA can’t be bound by β-Lactams Antibiotics
        1. The Antibiotics used in MRSA/MRSP infections are Rifampicin (AMEG A) and Amikacin, Florfenicol (AMEG C)
          1. Also: Mupirocin, Fusidic Acid, Nitrofurantoine (UTI only)

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