Chapter 83
Basic Principles of Antimicrobial
Therapy
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Antimicrobials
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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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Basic Principles of
Antimicrobial Therapy
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Chemotherapy
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Antibiotic
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Use of chemicals against invading organisms
Strictly speaking—a chemical that is produced by
one microbe and has the ability to harm other
microbes
Antimicrobial agent
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Any agent that has the ability to kill or suppress
microorganisms
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Selective Toxicity
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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
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Various themes used to classify
The two used for this textbook:
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Classification by susceptible organism
Classification by mechanism of action
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Classification of Antibiotics
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Drugs work on:
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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
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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
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Enterococcus faecium, Staphylococcus
aureus, Enterobacter species, Klebsiella
species, Pseudomonas aeruginosa,
Acinetobacter baumannii, Clostridium difficile
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Microbial Mechanisms of
Drug Resistance
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Four basic actions
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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.
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Mechanisms for
Acquired Resistance
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Spontaneous mutation
Conjugation
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Antibiotic Use and DrugResistant Microbe Emergence
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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.
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Delaying Emergence of
Drug Resistance
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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.
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Delaying Emergence of
Drug Resistance
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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.
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Selection of Antibiotics
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Identify organism
Drug sensitivity of organism
Host factors
Drug may be ruled out owing to
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Allergy
Inability to penetrate the site of infection
Patient variables
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Empiric Therapy
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Antibiotic therapy for patients before
causative organism is positively identified
Drug selection based on
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Clinical evaluation
Knowledge of microbes most likely to have caused
infection
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Identifying the Infection Organism
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Match the drug with the bug
Gram-stained preparation
Determining drug susceptibility
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Disk diffusion test
Broth dilution procedure
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Host Factors
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Host defenses
Site of infection
Age
Pregnancy and lactation
Previous allergic reactions
Genetic factors
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Dosage Size and Duration
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Antibiotic must be present:
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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
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Antimicrobial effects of antibiotic
combinations
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Indications
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Additive, potentiative, antagonistic
Mixed infections, prevention of resistance,
decreased toxicity, and enhanced bacterial action
Disadvantages of combinations
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Prophylactic Use of Antimicrobials
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Agents given to prevent infection rather than
to treat an established infection
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Surgery
Bacterial endocarditis
Neutropenia
Other indications
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Misuses of Antimicrobial Drugs
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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
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Monitoring of Antimicrobial Therapy
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Monitor clinical responses and laboratory
results
Frequency of monitoring should increase with
severity of infection
Clinical indicators of success
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Reduction of fever, resolution of signs/symptoms
related to the affected organ
Serum drug levels for toxicity
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