--- module: 037-01 language: en chapter: 37 title: "Antibacterial, Antiviral, Antifungal, and Antiparasitic Therapy" module_title: "Foundations" source_sha256: 6cfa4e98fe87a63183a6a19c5105f88c7043a39e3cfa6e123c288ed6e4ab10c3 --- # Antimicrobial therapy foundations ## Orientation ### Success: active drug at site, vulnerable pathogen #### Plus source control and host clearance ### Choice integrates syndrome, organisms, resistance #### Allergy, organ function, pregnancy, interactions ### Empirical breadth saves life but selects resistance ## Selective toxicity and exposure ### Targets: walls, ribosomes, viral enzymes, ergosterol ### Selectivity is relative #### Mitochondria, eukaryotic fungi, shared parasite pathways ### Pharmacokinetics: concentration over time ### Pharmacodynamics: exposure related to killing #### Time above MIC, peak to MIC, or area under curve ### Bactericidal versus bacteriostatic #### Does not automatically rank clinical effectiveness ### Difficult sites need penetration and source control ## Cell-wall-active antibacterials ### Beta-lactams bind penicillin-binding proteins #### Disrupt peptidoglycan cross-linking, time-dependent ### Allergy labels often inaccurate #### Testing restores safer narrow options ### Resistance: beta-lactamases, altered targets, efflux #### Inhibitors do not block every enzyme #### ESBL, AmpC, carbapenemases differ ### Glycopeptides bind wall precursors, Gram-positive #### Vancomycin monitored for efficacy and kidney toxicity #### Oral vancomycin acts only within gut ## Protein-synthesis inhibitors ### Aminoglycosides: thirty-S, mistranslation #### Concentration-dependent killing of aerobic Gram-negatives #### Anaerobes lack oxygen-dependent uptake #### Kidney, vestibular, auditory toxicity ### Tetracyclines block aminoacyl transfer-RNA binding ### Macrolides inhibit fifty-S translocation #### QT prolongation and interactions ### Clindamycin suppresses toxin production #### Strong Clostridioides difficile risk ### Linezolid blocks initiation #### Prolonged use: cytopenias, neuropathy, lactic acidosis ## Nucleic-acid and metabolic inhibitors ### Fluoroquinolones inhibit gyrase and topoisomerase #### Tendon, nerve, glucose, QT, C. difficile harms #### Resistance readily, so not for convenience ### Rifamycins inhibit RNA polymerase #### Monotherapy for tuberculosis breeds resistance #### Enzyme induction alters many drugs ### Sulfonamide and trimethoprim block folate sequence #### Hyperkalaemia, marrow, haemolysis in G6PD deficiency ### Metronidazole: toxic intermediates in low oxygen ## Membrane-active and specialised agents ### Daptomycin inactivated by surfactant #### Cannot treat pneumonia ### Nitrofurantoin concentrates only in urine ### Tuberculosis uses multiple drugs #### Large heterogeneous populations select resistance ## Resistance mechanisms ### Destroy drug, alter target, reduce entry, efflux ### Intrinsic or acquired by mutation and transfer ### Biofilm and persisters give tolerance ### Combination: breadth, synergy, resistance prevention #### Costs: toxicity, antagonism, ecological pressure #### De-escalate once cultures clarify need ## Antiviral therapy ### Replication peaks early, so timing matters ### Latent genomes persist despite suppression ### Nucleoside analogues corrupt genome synthesis #### Herpes resistance rises with immune impairment ### Neuraminidase inhibitors work best early ### HIV combination prevents resistance and transmission ### Hepatitis B suppressed, hepatitis C curable ## Antifungal therapy ### Polyenes bind ergosterol #### Amphotericin: infusion, kidney, potassium loss ### Azoles inhibit ergosterol synthesis #### Differ in QT, liver, cytochrome interactions ### Echinocandins inhibit beta-glucan synthesis ### Flucytosine combined as resistance emerges fast ### Outcome depends on immune recovery, device removal ### Colonisation is not invasion ## Antiparasitic therapy and safe prescribing ### Malaria: species, geography, severity #### Dormant liver forms need G6PD check ### Killing helminths can provoke inflammation ### Treat Strongyloides before immunosuppression #### Hyperinfection can be fatal ### Failure: pus, obstruction, device, wrong diagnosis #### Longer is not automatically better ### Switch intravenous to oral when conditions permit