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  <head>
    <title>037-02 Exposure-targeted antimicrobial treatment and resistance-aware prescribing</title>
    <ownerName>Integrated Medical Foundations</ownerName>
  </head>
  <body>
    <outline text="Exposure-targeted, resistance-aware prescribing">
      <outline text="Prescription as a quantitative hypothesis">
        <outline text="Free-drug exposure at site, without unacceptable harm"/>
        <outline text="Susceptible cannot fix undrained abscess">
          <outline text="Or obstructed kidney, infected prosthesis"/>
        </outline>
        <outline text="Review diagnosis, organism, site, source, host"/>
      </outline>
      <outline text="Pharmacodynamic targets">
        <outline text="Beta-lactams: time above inhibitory concentration">
          <outline text="Shorter interval or extended infusion"/>
        </outline>
        <outline text="Aminoglycosides: high peak, post-antibiotic effect">
          <outline text="Large separated doses in suitable patients"/>
        </outline>
        <outline text="Vancomycin, fluoroquinolones: area under curve"/>
        <outline text="Indices are population models, not guarantees"/>
      </outline>
      <outline text="Critical illness and dose individualisation">
        <outline text="Capillary leak expands hydrophilic distribution">
          <outline text="Lower initial concentration"/>
        </outline>
        <outline text="Clearance reduced or augmented"/>
        <outline text="Dialysis and circuits remove or sequester drug"/>
        <outline text="Loading dose follows distribution">
          <outline text="Still needed in renal failure"/>
          <outline text="Maintenance follows clearance"/>
        </outline>
        <outline text="Body weight types not interchangeable"/>
        <outline text="Renal equations fail during acute change"/>
        <outline text="Mistimed levels cannot be interpreted">
          <outline text="Levels update a patient-specific model"/>
        </outline>
      </outline>
      <outline text="Tissue penetration">
        <outline text="Free drug, lipid solubility, ionisation, barriers"/>
        <outline text="Inflamed meninges admit some beta-lactams">
          <outline text="Cerebrospinal targets stricter than serum"/>
        </outline>
        <outline text="Nitrofurantoin: high urine, low tissue levels"/>
        <outline text="Daptomycin neutralised by surfactant"/>
        <outline text="Aminoglycosides poor in acidic anaerobic abscess"/>
        <outline text="Match the infected compartment"/>
      </outline>
      <outline text="Beta-lactam allergy">
        <outline text="History: drug, timing, symptoms, later tolerance"/>
        <outline text="Gastrointestinal upset is intolerance"/>
        <outline text="Mild remote rash versus immediate or severe reaction"/>
        <outline text="Challenge or testing removes inaccurate labels">
          <outline text="Planned, not in unstable acute infection"/>
        </outline>
        <outline text="Desensitisation gives temporary tolerance">
          <outline text="Lost when the drug is interrupted"/>
        </outline>
        <outline text="Severe reactions: avoid re-exposure"/>
      </outline>
      <outline text="Resistance and toxicity monitoring">
        <outline text="Beta-lactamases differ in substrate and inhibitor">
          <outline text="Inducible AmpC may emerge on therapy"/>
          <outline text="Carbapenemases compromise last-line drugs"/>
        </outline>
        <outline text="Altered binding proteins: methicillin resistance"/>
        <outline text="Molecular markers need phenotypic confirmation"/>
        <outline text="Aminoglycosides: kidney, vestibular, cochlear toxicity">
          <outline text="Tinnitus or imbalance may precede creatinine"/>
        </outline>
        <outline text="Vancomycin targets calculated exposure">
          <outline text="Infusion flushing is not IgE anaphylaxis"/>
        </outline>
        <outline text="Monitoring also secures minimum exposure"/>
      </outline>
      <outline text="Class-specific antibacterial choices">
        <outline text="Macrolides, tetracyclines enter cells">
          <outline text="Cover atypical respiratory organisms"/>
        </outline>
        <outline text="Linezolid: oral, lung penetration">
          <outline text="Prolonged use harms marrow, nerves, mitochondria"/>
        </outline>
        <outline text="Fluoroquinolones powerful but ecologically costly">
          <outline text="Chelation by metals reduces absorption"/>
        </outline>
        <outline text="Rifampicin alone breeds resistance">
          <outline text="Enzyme induction causes drug failures"/>
        </outline>
      </outline>
      <outline text="Combination therapy">
        <outline text="Four purposes: breadth, polymicrobial, synergy">
          <outline text="And suppressing single-step resistance"/>
        </outline>
        <outline text="Stop overlap once microbiology is clear"/>
        <outline text="Double Gram-negative cover rarely helps later"/>
        <outline text="Tuberculosis and HIV justify combinations"/>
      </outline>
      <outline text="Antiviral, antifungal, antiparasitic exposure">
        <outline text="Herpes drugs need phosphorylation first"/>
        <outline text="Late influenza treatment in severe disease">
          <outline text="Pneumonia can worsen from inflammation"/>
        </outline>
        <outline text="Interrupted antiretrovirals select resistance"/>
        <outline text="Azole exposure varies with food, acid, interactions"/>
        <outline text="Echinocandins poor in urine, eye, brain"/>
        <outline text="Reverse the fungal ecological advantage">
          <outline text="Respiratory Candida is usually colonisation"/>
          <outline text="Blood Candida needs systemic therapy"/>
        </outline>
        <outline text="Severe malaria needs urgent parenteral therapy"/>
        <outline text="Hypnozoite eradication after G6PD assessment"/>
      </outline>
      <outline text="Failure review and ending therapy">
        <outline text="Structured review, not reflexive broadening">
          <outline text="Pus, obstruction, necrosis, foreign material"/>
        </outline>
        <outline text="Timeout: continue, narrow, oralise, or stop"/>
        <outline text="Toxicity monitoring continues during improvement"/>
        <outline text="Duration from syndrome and evidence, not habit"/>
        <outline text="Intravenous route not inherently stronger"/>
        <outline text="Least harmful regimen that completes cure"/>
      </outline>
    </outline>
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