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Rational Antibiotic Use and Resistance

This document discusses the rational use of antibiotics. It notes that antibiotics are commonly used drugs that account for a large portion of healthcare expenditures. However, studies show high rates of inappropriate antibiotic use. The document emphasizes the need for appropriate use to avoid adverse effects, emergence of antibiotic resistance, and unnecessary healthcare costs. It provides guidance on determining if an antibiotic is necessary, choosing the most appropriate antibiotic based on the pathogen, patient factors, and antibiotic properties. It also discusses optimal dosing and treatment duration based on pharmacokinetic and pharmacodynamic principles. The overall message is that judicious antibiotic use is needed to prolong the effectiveness of our current antibiotics.

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daniela
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122 views28 pages

Rational Antibiotic Use and Resistance

This document discusses the rational use of antibiotics. It notes that antibiotics are commonly used drugs that account for a large portion of healthcare expenditures. However, studies show high rates of inappropriate antibiotic use. The document emphasizes the need for appropriate use to avoid adverse effects, emergence of antibiotic resistance, and unnecessary healthcare costs. It provides guidance on determining if an antibiotic is necessary, choosing the most appropriate antibiotic based on the pathogen, patient factors, and antibiotic properties. It also discusses optimal dosing and treatment duration based on pharmacokinetic and pharmacodynamic principles. The overall message is that judicious antibiotic use is needed to prolong the effectiveness of our current antibiotics.

Uploaded by

daniela
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd

The Rational Use of

Antibiotics
Victor Lim
International Medical University
Kuala Lumpur, Malaysia
Antibiotics
 One of the most commonly used
group of drugs
 In USA 23 million kg used annually;
50% for medical reasons
 May account for up to 50% of a
hospital’s drug expenditure
 Studies worldwide has shown a high
incidence of inappropriate use
Reasons for appropriate use
 Avoid adverse effects on the patient
 Avoid emergence of antibiotic
resistance - ecological or societal
aspect of antibiotics
 Avoid unnecessary increases in the
cost of health care
Ecological/Societal Aspect
 Antibiotics differ from other classes of
drugs
 The way in which a physician and other
professionals use an antibiotic can affect
the response of future patients
 Responsibility to society
 Antibiotic resistance can spread from
 bacteria to bacteria
 patient to patient
 animals to patients
Prescribing an antibiotic
 Is an antibiotic necessary ?
 What is the most appropriate
antibiotic ?
 What dose, frequency, route and
duration ?
 Is the treatment effective ?
Is an antibiotic necessary ?
 Useful only for the treatment of
bacterial infections
 Not all fevers are due to infection
 Not all infections are due to bacteria
 There is no evidence that antibiotics will
prevent secondary bacterial infection in
patients with viral infection
Arroll and Kenealy, Antibiotics for the common
cold. Cochrane Database of Systematic Reviews.
Issue 4, 2003

Meta-analysis of 9 randomised placebo


controlled trials involving 2249 patients

Conclusions: There is not enough evidence of


important benefits from the treatment of upper
respiratory tract infections with antibiotics and
there is a significant increase in adverse
effects associated with antibiotic use.
Is an antibiotic necessary ?
 Not all bacterial infections require
antibiotics
 Consider other options :
 antiseptics
 surgery
Choice of an antibiotic

 Aetiological agent
 Patient factors
 Antibiotic factors
The aetiological agent
 Clinical diagnosis
 clinical acumen
 the most likely site/source of
infection
 the most likely pathogens
 empirical therapy
 universal data
 local data
Importance of local antibiotic
resistance data
 Resistance patterns vary
 From country to country
 From hospital to hospital in the same
country
 From unit to unit in the same hospital
 Regional/Country data useful only for
looking at trends NOT guide empirical
therapy
The aetiological agent
 Laboratory diagnosis
 interpretation of the report
 what is isolated is not necessarily
the pathogen
 was the specimen properly
collected ?
 is it a contaminant or coloniser ?
 sensitivity reports are at best a
guide
Patient factors
 Age
 Physiological functions
 Genetic factors
 Pregnancy
 Site and severity of infection
 Allergy
Antibiotic factors
 Pharmacokinetic/pharmacodynamic
(PK/PD) profile
 absorption
 excretion
 tissue levels
 peak levels, AUC, Time above MIC
 Toxicity and other adverse effects
 Drug-drug interactions
 Cost
PK/PD Parameters
 Increasing knowledge on the
association between PK/PD parameters
on clinical efficacy and preventing
emergence of resistance
 Enabled doctors to optimise dosage
regimens
 Led to redefinition of interpretative
breakpoints in sensitivity testing
Important
Important PK/PD Parameters
PK/PD Parameters
Time above MIC : 8

Antibiotic concentration (ug/ml)


Proportion of
6 Drug A
the dosing Drug A
interval when Drug B
4 Drug B
the drug
concentration 2
exceeds the B
B
MIC
0
A Time

Time above MIC


Important PK/PD Parameters

Area under the curve


AUC/MIC is the over MIC

concentration
Antibiotic
ratio of the AUC
PEAK
to MIC
Peak/MIC is the
ratio of the peak MIC

concentration to
MIC
Time
PK/PD and Antimicrobial Efficacy
 2 main patterns of bacterial killing
 Concentration dependent
 Aminoglycosides, quinolones, macrolides, azalides,
clindamycin, tetracyclines, glycopeptides,
oxazolidinones
 Correlated with AUC/MIC , Peak/MIC

 Time dependent with no persistent effect


 Betalactams
 Correlated with Time above MIC (T>MIC)

Craig, 4th ISAAR, Seoul 2003


Goal of therapy based on PK/PD
Pattern of Activity Antimicrobials Goal of therapy
and relevant
PK/PD Parameter

Concentration AMGs, Quinolones, Maximise


dependent killing Daptomycin, ketolides, concentrations;
Macrolides, azithro- AUC/MIC, peak/MIC
mycin, clindamycin, Use high doses;
streptogramines,tetracyc daily dosing for
lines, glycopeptides, some agents
oxazolidinones
Time dependent killing Betalactams Maximise duration
with no persistent of exposure; T>MIC
effects Use more frequent
dosing; longer
infusion times
including continuous
infusion
Cost of antibiotic
 Not just the unit cost of the antibiotic
 Materials for administration of drug
 Labour costs
 Expected duration of stay in hospital
 Cost of monitoring levels
 Expected compliance
Choice of regimen
 Oral vs parenteral
 Traditional view
 “serious = parenteral”
 previous lack of broad spectrum oral
antibiotics with reliable bioavailability
 Improved oral agents
 higher and more persistent serum and
tissue levels
 for certain infections as good as
parenteral
Advantages of oral treatment
 Eliminates risks of complications
associated with intravascular lines
 Shorter duration of hospital stay
 Savings in nursing time
 Savings in overall costs
Duration of treatment
 In most instances the optimum
duration is unknown
 Duration varies from a single dose to
many months depending on the
infection
 Shorter durations, higher doses
 For certain infections a minimum
duration is recommended
Recommended minimum
durations of treatment
Infection Minimum duration
Tuberculosis 4 - 6 months
Empyema/lung abscess 4 - 6 weeks
Endocarditis 4 weeks
Osteomyelitis 4 weeks
Atypical pneumonia 2 - 3 weeks
Pneumococcal meningitis 7 days
Pneumococcal 5 days
pneumonia
Monitoring efficacy
 Early review of response
 Routine early review
 Increasing or decreasing the level of
treatment depending on response
 change route
 change dose
 change spectrum of antibacterial
activity
 stopping antibiotic
Campaign to Prevent Antimicrobial Resistance in Healthcare Settings

Antimicrobial Resistance:
Key Prevention Strategies
Susceptible Pathogen
Antimicrobial-Resistant
Pathogen Pathogen
Prevent Prevent
Transmission Infection

Infection
Antimicrobial
Resistance
Effective
Optimize Diagnosis
& Treatment
Use

Antimicrobial Use
Campaign to Prevent Antimicrobial Resistance in Healthcare Settings

12 Steps to Prevent
Antimicrobial Resistance

12 Break the chain


11 Isolate the pathogen Prevent Transmission
10 Stop treatment when cured
9 Know when to say “no” to vanco
8 Treat infection, not colonization Use Antimicrobials Wisely
7 Treat infection, not contamination
6 Use local data
5 Practice antimicrobial control
4 Access the experts Diagnose & Treat Effectively
3 Target the pathogen
2 Get the catheters out
1 Vaccinate Prevent Infections
Conclusions
 Antibiotic resistance is a major
problem world-wide
 Resistance is inevitable with use
 No new class of antibiotic introduced
over the last two decades
 Appropriate use is the only way of
prolonging the useful life of an
antibiotic

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