CAM102 Lecture Notes - Lecture 16: Multiple Drug Resistance, Antibiotics, Critical Resistance
Lecture 2
Learning Concepts
• What principles govern the use of antibiotics?
• What methods are used to measure the activity of antibiotics?
• How does resistance to antibiotics occur?
• Does infection control help in managing antibiotic resistance?
• What new drugs are under development for the treatment of multi-drug resistant
tuberculosis?
Principles of Antimicrobial Use
The Antimicrobial Creed
M
Microbiology guides therapy wherever possible
I
Indications should be evidence-based
N
Narrowest spectrum therapy required
D
Dosage individualised to the patient and appropriate to the site and type of infection
M
Minimise duration of therapy
E
Ensure oral therapy is used where clinically appropriate
Antibiotic Therapies
Prophylactic Therapy
Aims to prevent infection when there is a significant clinical risk of infection developing
• Restrict to when evidence of efficacy or when consequences of infection would be associated
with significant morbidity or mortality
• Base antimicrobial choice on the likely pathogen
• Use a single perioperative dose sufficient to achieve adequate intraoperative tissue
concentration at the time contamination is most likely
Empirical Therapy
Treats an established infection when the causative agent has not been identified
• Restrict to when clear indication for therapy and likely clinical benefit
• Obtain specimens for laboratory diagnosis
• Base antimicrobial choice on the likely pathogen and antimicrobial susceptibility
• Review empirical therapy at 48 to 72 hours
• Obtain laboratory diagnostic and antimicrobial susceptibility information
Directed Therapy
Treats an established infection when the pathogen has been identified
• Critically evaluate laboratory results to distinguish infection from colonisation or
contamination
• Direct therapy in accordance with clinical guidelines using the most effective, least toxic and
narrowest spectrum drug available
• Use a single drug unless combination therapy is required for efficacy
• Optimise antimicrobial dosage, and monitor blood concentrations for drugs with a narrow
therapeutic index
• Use oral therapy when clinically appropriate
• Keep duration of therapy as short as possible
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Disk-Diffusion Method
For determining the activity of antibiotics against bacterial pathogens
• Culture of bacterial species to be tested is spread onto agar plates
• A disk of filter paper impregnated with a specific antibiotic is placed on the agar plate
• Sensitivity of the bacterial species to the antibiotic is seen as a zone of growth inhibition, the
diameter of which can be measured
Broth-Dilution Assay
For determining the Minimum Inhibitory Concentration (MIC) of antibiotics
• A series of increasing concentration of antibiotic is prepared in the culture medium
• Each tube is inoculated with the test organism and the tubes are incubated at the appropriate
growth conditions
• Growth (seen as turbidity) occurs in the tubes with antibiotic concentrations below the MIC
• The MIC is defined as the lowest concentrations of an antibiotic that completely inhibits the
growth of the test organism under a particular culture condition
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Etest (Epsilometer Test)
For determining the MIC of antibiotics
• A pre-defined gradient method of determining the antimicrobial susceptibility of antibiotics
involving a "ready-to-use" strip
• The Etest strip is placed on an agar surface which has been inoculated with the test bacterium
and the antibiotic gradient on the strip transfers to the agar
• Bacterial growth becomes visible after incubation and inhibition is seen as a symmetrical
ellipse centred along the strip
• The MIC value in µg/mL is read directly from the scale on the Etest strip at the point where the
ellipse edge intersects the strip
European Committee on Antimicrobial Susceptibility Testing
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Document Summary
Dosage individualised to the patient and appropriate to the site and type of infection. Ensure oral therapy is used where clinically appropriate. For determining the activity of antibiotics against bacterial pathogens: culture of bacterial species to be tested is spread onto agar plates, a disk of filter paper impregnated with a specific antibiotic is placed on the agar plate. Sensitivity of the bacterial species to the antibiotic is seen as a zone of growth inhibition, the diameter of which can be measured. Alexander fleming in his nobel lecture in 1945 warned that bacteria could become resistant to penicillin with little difficulty. Fleming"s concern was justified when within a few years of the clinical introduction of penicillin, streptomycin and other antibiotics, bacterial strains resistant to them began to emerge. What happens when the antibiotics stop working: there is a multitude of antibiotic-resistant pathogens such as methicillin-resistant.