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  <head>
    <title>037-01 Foundations</title>
    <ownerName>Integrated Medical Foundations</ownerName>
  </head>
  <body>
    <outline text="Antimicrobial therapy foundations">
      <outline text="Orientation">
        <outline text="Success: active drug at site, vulnerable pathogen">
          <outline text="Plus source control and host clearance"/>
        </outline>
        <outline text="Choice integrates syndrome, organisms, resistance">
          <outline text="Allergy, organ function, pregnancy, interactions"/>
        </outline>
        <outline text="Empirical breadth saves life but selects resistance"/>
      </outline>
      <outline text="Selective toxicity and exposure">
        <outline text="Targets: walls, ribosomes, viral enzymes, ergosterol"/>
        <outline text="Selectivity is relative">
          <outline text="Mitochondria, eukaryotic fungi, shared parasite pathways"/>
        </outline>
        <outline text="Pharmacokinetics: concentration over time"/>
        <outline text="Pharmacodynamics: exposure related to killing">
          <outline text="Time above MIC, peak to MIC, or area under curve"/>
        </outline>
        <outline text="Bactericidal versus bacteriostatic">
          <outline text="Does not automatically rank clinical effectiveness"/>
        </outline>
        <outline text="Difficult sites need penetration and source control"/>
      </outline>
      <outline text="Cell-wall-active antibacterials">
        <outline text="Beta-lactams bind penicillin-binding proteins">
          <outline text="Disrupt peptidoglycan cross-linking, time-dependent"/>
        </outline>
        <outline text="Allergy labels often inaccurate">
          <outline text="Testing restores safer narrow options"/>
        </outline>
        <outline text="Resistance: beta-lactamases, altered targets, efflux">
          <outline text="Inhibitors do not block every enzyme"/>
          <outline text="ESBL, AmpC, carbapenemases differ"/>
        </outline>
        <outline text="Glycopeptides bind wall precursors, Gram-positive">
          <outline text="Vancomycin monitored for efficacy and kidney toxicity"/>
          <outline text="Oral vancomycin acts only within gut"/>
        </outline>
      </outline>
      <outline text="Protein-synthesis inhibitors">
        <outline text="Aminoglycosides: thirty-S, mistranslation">
          <outline text="Concentration-dependent killing of aerobic Gram-negatives"/>
          <outline text="Anaerobes lack oxygen-dependent uptake"/>
          <outline text="Kidney, vestibular, auditory toxicity"/>
        </outline>
        <outline text="Tetracyclines block aminoacyl transfer-RNA binding"/>
        <outline text="Macrolides inhibit fifty-S translocation">
          <outline text="QT prolongation and interactions"/>
        </outline>
        <outline text="Clindamycin suppresses toxin production">
          <outline text="Strong Clostridioides difficile risk"/>
        </outline>
        <outline text="Linezolid blocks initiation">
          <outline text="Prolonged use: cytopenias, neuropathy, lactic acidosis"/>
        </outline>
      </outline>
      <outline text="Nucleic-acid and metabolic inhibitors">
        <outline text="Fluoroquinolones inhibit gyrase and topoisomerase">
          <outline text="Tendon, nerve, glucose, QT, C. difficile harms"/>
          <outline text="Resistance readily, so not for convenience"/>
        </outline>
        <outline text="Rifamycins inhibit RNA polymerase">
          <outline text="Monotherapy for tuberculosis breeds resistance"/>
          <outline text="Enzyme induction alters many drugs"/>
        </outline>
        <outline text="Sulfonamide and trimethoprim block folate sequence">
          <outline text="Hyperkalaemia, marrow, haemolysis in G6PD deficiency"/>
        </outline>
        <outline text="Metronidazole: toxic intermediates in low oxygen"/>
      </outline>
      <outline text="Membrane-active and specialised agents">
        <outline text="Daptomycin inactivated by surfactant">
          <outline text="Cannot treat pneumonia"/>
        </outline>
        <outline text="Nitrofurantoin concentrates only in urine"/>
        <outline text="Tuberculosis uses multiple drugs">
          <outline text="Large heterogeneous populations select resistance"/>
        </outline>
      </outline>
      <outline text="Resistance mechanisms">
        <outline text="Destroy drug, alter target, reduce entry, efflux"/>
        <outline text="Intrinsic or acquired by mutation and transfer"/>
        <outline text="Biofilm and persisters give tolerance"/>
        <outline text="Combination: breadth, synergy, resistance prevention">
          <outline text="Costs: toxicity, antagonism, ecological pressure"/>
          <outline text="De-escalate once cultures clarify need"/>
        </outline>
      </outline>
      <outline text="Antiviral therapy">
        <outline text="Replication peaks early, so timing matters"/>
        <outline text="Latent genomes persist despite suppression"/>
        <outline text="Nucleoside analogues corrupt genome synthesis">
          <outline text="Herpes resistance rises with immune impairment"/>
        </outline>
        <outline text="Neuraminidase inhibitors work best early"/>
        <outline text="HIV combination prevents resistance and transmission"/>
        <outline text="Hepatitis B suppressed, hepatitis C curable"/>
      </outline>
      <outline text="Antifungal therapy">
        <outline text="Polyenes bind ergosterol">
          <outline text="Amphotericin: infusion, kidney, potassium loss"/>
        </outline>
        <outline text="Azoles inhibit ergosterol synthesis">
          <outline text="Differ in QT, liver, cytochrome interactions"/>
        </outline>
        <outline text="Echinocandins inhibit beta-glucan synthesis"/>
        <outline text="Flucytosine combined as resistance emerges fast"/>
        <outline text="Outcome depends on immune recovery, device removal"/>
        <outline text="Colonisation is not invasion"/>
      </outline>
      <outline text="Antiparasitic therapy and safe prescribing">
        <outline text="Malaria: species, geography, severity">
          <outline text="Dormant liver forms need G6PD check"/>
        </outline>
        <outline text="Killing helminths can provoke inflammation"/>
        <outline text="Treat Strongyloides before immunosuppression">
          <outline text="Hyperinfection can be fatal"/>
        </outline>
        <outline text="Failure: pus, obstruction, device, wrong diagnosis">
          <outline text="Longer is not automatically better"/>
        </outline>
        <outline text="Switch intravenous to oral when conditions permit"/>
      </outline>
    </outline>
  </body>
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