Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 83 Basic Principles of Antimicrobial Therapy
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
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
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
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
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
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
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
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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.10 Mechanisms for Acquired Resistance Spontaneous mutation Conjugation
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)
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
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
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
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
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
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
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
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
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
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
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