Chapter 83

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


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


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


Classification of Antimicrobial Drugs

Various themes used to classify The two used for this textbook:

Classification by susceptible organism Classification by mechanism of action


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


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


Organisms With Microbial Drug Resistance

Enterococcus faecium, Staphylococcus aureus, Enterobacter species, Klebsiella species, Pseudomonas aeruginosa, Acinetobacter baumannii, Clostridium difficile


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


Mechanisms for Acquired Resistance

Spontaneous mutation Conjugation


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)


Delaying Emergence of Drug Resistance

Vaccinate Get the catheters out Target the pathogen Access the experts Practice antimicrobial control Use local data


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


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


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


Identifying the Infection Organism Match the drug with the bug Gram-stained preparation Determining drug susceptibility

Disk diffusion test Broth dilution procedure


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


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


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


Prophylactic Use of Antimicrobials Agents given to prevent infection rather than

to treat an established infection Surgery Bacterial endocarditis Neutropenia Other indications


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


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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Chapter 83

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