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Chapter 83

Chapter 83. Basic Principles of Antimicrobial Therapy. Antimicrobials. Used to treat infectious diseases Up to 30% of all hospitalized patients receive antimicrobials Modern antimicrobials—1930s and 1940s Significantly reduced morbidity and mortality from infection.

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Chapter 83

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  1. Chapter 83 Basic Principles of Antimicrobial Therapy

  2. Antimicrobials • Used to treat infectious diseases • Up to 30% of all hospitalized patients receive antimicrobials • Modern antimicrobials—1930s and 1940s • Significantly reduced morbidity and mortality from infection

  3. Basic Principles of Antimicrobial Therapy • Chemotherapy • Use of chemicals against invading organisms • Antibiotic • Strictly speaking—a chemical that is produced by one microbe and has the ability to harm other microbes • Antimicrobial agent • Any agent that has the ability to kill or suppress microorganisms

  4. Selective Toxicity • Toxic to microbes—harmless to host • Disruption of bacterial cell wall • Inhibition of an enzyme unique to bacteria • Disruption of bacterial protein synthesis

  5. Classification of Antimicrobial Drugs • Various themes used to classify • The two used for this textbook: • Classification by susceptible organism • Classification by mechanism of action

  6. Classification of Antibiotics • Drugs work on: • Cell wall synthesis • Cell membrane permeability • Protein synthesis (lethal) • Nonlethal inhibitors of protein synthesis • Synthesis of nucleic acids • Antimetabolites • Viral enzyme inhibitors

  7. Acquired Resistance to Antimicrobial Drugs • Over time, organisms develop resistance • May have been highly responsive and then became less susceptible to one or more drugs

  8. Organisms With Microbial Drug Resistance • Enterococcus faecium, Staphylococcus aureus, Enterobacter species, Klebsiella species, Pseudomonas aeruginosa, Acinetobacter baumannii, Clostridium difficile

  9. Microbial Mechanisms of Drug Resistance • Four basic actions • Decrease the concentration of a drug at its site of action • Inactivate a drug • Alter the structure of drug target molecules • Produce a drug antagonist

  10. Mechanisms for Acquired Resistance • Spontaneous mutation • Conjugation

  11. Antibiotic Use and Drug-Resistant Microbe Emergence • How antibiotic use promotes resistance • Which antibiotics promote resistance • The amount of antibiotic impacts resistance • Nosocomial infections • Suprainfection (superinfection)

  12. Delaying Emergence of Drug Resistance • Vaccinate • Get the catheters out • Target the pathogen • Access the experts • Practice antimicrobial control • Use local data

  13. Delaying Emergence of Drug Resistance • Treat infection, not contamination • Treat infection, not colonization • Know when to say “No to vanco” • Stop treatment when infection is cured or unlikely • Isolate the pathogen • Break the chain of contagion

  14. Selection of Antibiotics • Identify organism • Drug sensitivity of organism • Host factors • Drug may be ruled out owing to • Allergy • Inability to penetrate the site of infection • Patient variables

  15. Empiric Therapy • Antibiotic therapy for patients before causative organism is positively identified • Drug selection based on • Clinical evaluation • Knowledge of microbes most likely to have caused infection

  16. Identifying the Infection Organism • Match the drug with the bug • Gram-stained preparation • Determining drug susceptibility • Disk diffusion test • Broth dilution procedure

  17. Host Factors • Host defenses • Site of infection • Age • Pregnancy and lactation • Previous allergic reactions • Genetic factors

  18. Dosage Size and Duration • Antibiotic must be present: • At the site of infection • For a sufficient length of time • Antibiotics must not be discontinued prematurely • Teach patients to complete full prescription

  19. Antibiotic Combinations • Antimicrobial effects of antibiotic combinations • Additive, potentiative, antagonistic • Indications • Mixed infections, prevention of resistance, decreased toxicity, and enhanced bacterial action • Disadvantages of combinations

  20. Prophylactic Use of Antimicrobials • Agents given to prevent infection rather than to treat an established infection • Surgery • Bacterial endocarditis • Neutropenia • Other indications

  21. Misuses of Antimicrobial Drugs • Attempted treatment of untreatable infections • Treatment of fever of unknown origin • Improper dosage • Treatment in the absence of adequate bacteriologic information • Omission of surgical drainage

  22. Monitoring of Antimicrobial Therapy • Monitor clinical responses and laboratory results • Frequency of monitoring should increase with severity of infection • Clinical indicators of success • Reduction of fever, resolution of signs/symptoms related to the affected organ • Serum drug levels for toxicity

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