1. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 83 Basic Principles of Antimicrobial Therapy

2. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.8 Organisms With Microbial Drug Resistance  Enterococcus faecium, Staphylococcus aureus, Enterobacter species, Klebsiella species, Pseudomonas aeruginosa, Acinetobacter baumannii, Clostridium difficile

9. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.10 Mechanisms for Acquired Resistance  Spontaneous mutation  Conjugation

11. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.12 Delaying Emergence of Drug Resistance  Vaccinate  Get the catheters out  Target the pathogen  Access the experts  Practice antimicrobial control  Use local data

13. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.16 Identifying the Infection Organism  Match the drug with the bug  Gram-stained preparation  Determining drug susceptibility  Disk diffusion test  Broth dilution procedure

17. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.17 Host Factors  Host defenses  Site of infection  Age  Pregnancy and lactation  Previous allergic reactions  Genetic factors

18. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.20 Prophylactic Use of Antimicrobials  Agents given to prevent infection rather than to treat an established infection  Surgery  Bacterial endocarditis  Neutropenia  Other indications

21. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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