--- module: 037-02 language: en chapter: 37 title: "Antibacterial, Antiviral, Antifungal, and Antiparasitic Therapy" module_title: "Exposure-targeted antimicrobial treatment and resistance-aware prescribing" source_sha256: 2e8ac568fe5450e70521bf2251441a0796b01559e624b2b97822e74e15d5342e --- # Exposure-targeted, resistance-aware prescribing ## Prescription as a quantitative hypothesis ### Free-drug exposure at site, without unacceptable harm ### Susceptible cannot fix undrained abscess #### Or obstructed kidney, infected prosthesis ### Review diagnosis, organism, site, source, host ## Pharmacodynamic targets ### Beta-lactams: time above inhibitory concentration #### Shorter interval or extended infusion ### Aminoglycosides: high peak, post-antibiotic effect #### Large separated doses in suitable patients ### Vancomycin, fluoroquinolones: area under curve ### Indices are population models, not guarantees ## Critical illness and dose individualisation ### Capillary leak expands hydrophilic distribution #### Lower initial concentration ### Clearance reduced or augmented ### Dialysis and circuits remove or sequester drug ### Loading dose follows distribution #### Still needed in renal failure #### Maintenance follows clearance ### Body weight types not interchangeable ### Renal equations fail during acute change ### Mistimed levels cannot be interpreted #### Levels update a patient-specific model ## Tissue penetration ### Free drug, lipid solubility, ionisation, barriers ### Inflamed meninges admit some beta-lactams #### Cerebrospinal targets stricter than serum ### Nitrofurantoin: high urine, low tissue levels ### Daptomycin neutralised by surfactant ### Aminoglycosides poor in acidic anaerobic abscess ### Match the infected compartment ## Beta-lactam allergy ### History: drug, timing, symptoms, later tolerance ### Gastrointestinal upset is intolerance ### Mild remote rash versus immediate or severe reaction ### Challenge or testing removes inaccurate labels #### Planned, not in unstable acute infection ### Desensitisation gives temporary tolerance #### Lost when the drug is interrupted ### Severe reactions: avoid re-exposure ## Resistance and toxicity monitoring ### Beta-lactamases differ in substrate and inhibitor #### Inducible AmpC may emerge on therapy #### Carbapenemases compromise last-line drugs ### Altered binding proteins: methicillin resistance ### Molecular markers need phenotypic confirmation ### Aminoglycosides: kidney, vestibular, cochlear toxicity #### Tinnitus or imbalance may precede creatinine ### Vancomycin targets calculated exposure #### Infusion flushing is not IgE anaphylaxis ### Monitoring also secures minimum exposure ## Class-specific antibacterial choices ### Macrolides, tetracyclines enter cells #### Cover atypical respiratory organisms ### Linezolid: oral, lung penetration #### Prolonged use harms marrow, nerves, mitochondria ### Fluoroquinolones powerful but ecologically costly #### Chelation by metals reduces absorption ### Rifampicin alone breeds resistance #### Enzyme induction causes drug failures ## Combination therapy ### Four purposes: breadth, polymicrobial, synergy #### And suppressing single-step resistance ### Stop overlap once microbiology is clear ### Double Gram-negative cover rarely helps later ### Tuberculosis and HIV justify combinations ## Antiviral, antifungal, antiparasitic exposure ### Herpes drugs need phosphorylation first ### Late influenza treatment in severe disease #### Pneumonia can worsen from inflammation ### Interrupted antiretrovirals select resistance ### Azole exposure varies with food, acid, interactions ### Echinocandins poor in urine, eye, brain ### Reverse the fungal ecological advantage #### Respiratory Candida is usually colonisation #### Blood Candida needs systemic therapy ### Severe malaria needs urgent parenteral therapy ### Hypnozoite eradication after G6PD assessment ## Failure review and ending therapy ### Structured review, not reflexive broadening #### Pus, obstruction, necrosis, foreign material ### Timeout: continue, narrow, oralise, or stop ### Toxicity monitoring continues during improvement ### Duration from syndrome and evidence, not habit ### Intravenous route not inherently stronger ### Least harmful regimen that completes cure