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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
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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
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Classification of Antimicrobial Drugs
Various themes used to classify The two used for this textbook:
Classification by susceptible organism Classification by mechanism of action
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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
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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
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Organisms With Microbial Drug Resistance
Enterococcus faecium, Staphylococcus aureus, Enterobacter species, Klebsiella species, Pseudomonas aeruginosa, Acinetobacter baumannii, Clostridium difficile
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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
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Mechanisms for Acquired Resistance
Spontaneous mutation Conjugation
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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)
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Delaying Emergence of Drug Resistance
Vaccinate Get the catheters out Target the pathogen Access the experts Practice antimicrobial control Use local data
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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
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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
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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
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Identifying the Infection Organism
Match the drug with the bug Gram-stained preparation Determining drug susceptibility
Disk diffusion test Broth dilution procedure
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Host Factors
Host defenses Site of infection Age Pregnancy and lactation Previous allergic reactions Genetic factors
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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
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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
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Prophylactic Use of Antimicrobials
Agents given to prevent infection rather than to treat an established infection Surgery Bacterial endocarditis Neutropenia Other indications
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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