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7/31/2019 Rational Use of Anitibiotic
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The Rational Use of
AntibioticsVictor Lim
International Medical UniversityKuala Lumpur, Malaysia
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Antibiotics
One of the most commonly usedgroup of drugs
In USA 23 million kg used annually;50% for medical reasons
May account for up to 50% of a
hospitals drug expenditure Studies worldwide has shown a high
incidence of inappropriate use
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Reasons for appropriate use
Avoid adverse effects on the patient
Avoid emergence of antibiotic
resistance - ecological or societalaspect of antibiotics
Avoid unnecessary increases in the
cost of health care
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Ecological/Societal Aspect
Antibiotics differ from other classes ofdrugs
The way in which a physician and otherprofessionals use an antibiotic can affectthe response of future patients
Responsibility to society
Antibiotic resistance can spread from bacteria to bacteria patient to patient animals to patients
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Prescribing an antibiotic
Is an antibiotic necessary ?
What is the most appropriate
antibiotic ?
What dose, frequency, route andduration ?
Is the treatment effective ?
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Is an antibiotic necessary ?
Useful only for the treatment ofbacterial 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 inpatients with viral infection
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Arroll and Kenealy, Antibiotics for the commoncold. Cochrane Database of Systematic Reviews.Issue 4, 2003
Meta-analysis of 9 randomised placebocontrolled trials involving 2249 patients
Conclusions: There is not enough evidence ofimportant benefits from the treatment of upperrespiratory tract infections with antibiotics andthere is a significant increase in adverseeffects associated with antibiotic use.
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Is an antibiotic necessary ?
Not all bacterial infections requireantibiotics
Consider other options :
antiseptics
surgery
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Choice of an antibiotic
Aetiological agent
Patient factors Antibiotic factors
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The aetiological agent
Clinical diagnosis
clinical acumen
the most likely site/source ofinfection
the most likely pathogens
empirical therapyuniversal data
local data
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Importance of local antibiotic
resistance data Resistance patterns vary
From country to country
From hospital to hospital in the samecountry
From unit to unit in the same hospital
Regional/Country data useful only forlooking at trends NOT guide empiricaltherapy
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The aetiological agent
Laboratory diagnosis
interpretation of the report
what is isolated is not necessarilythe pathogen
was the specimen properly
collected ? is it a contaminant or coloniser ?
sensitivity reports are at best a
guide
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Patient factors
Age
Physiological functions
Genetic factors
Pregnancy
Site and severity of infection Allergy
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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
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PK/PD Parameters
Increasing knowledge on theassociation between PK/PD parameters
on clinical efficacy and preventingemergence of resistance
Enabled doctors to optimise dosageregimens
Led to redefinition of interpretativebreakpoints in sensitivity testing
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Important PK/PD Parameters
Time above MIC :Proportion ofthe dosing
interval whenthe drugconcentrationexceeds the
MIC
Time above MIC
Time
An
tibioticconcentration(ug/ml)
2
Drug A
Drug B
A
B
4
6
8
0
Important PK/PD Parameters
Drug A
Drug B
B
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Important PK/PD Parameters
AUC/MICis theratio of the AUC
to MICPeak/MICis the
ratio of the peakconcentration toMIC
Antibiotic
concentration
MIC
Time
Area under the curveover MIC
PEAK
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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
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Goal of therapy based on PK/PDPattern of Activity Antimicrobials Goal of therapy
and relevant
PK/PD Parameter
Concentrationdependent killing
AMGs, Quinolones,Daptomycin, ketolides,Macrolides, azithro-
mycin, clindamycin,streptogramines,tetracyclines, glycopeptides,oxazolidinones
Maximiseconcentrations;AUC/MIC, peak/MIC
Use high doses;daily dosing forsome agents
Time dependent killing
with no persistenteffects
Betalactams Maximise duration
of exposure; T>MICUse more frequentdosing; longerinfusion timesincluding continuous
infusion
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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
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Choice of regimen
Oral vs parenteral Traditional view
serious = parenteral
previous lack of broad spectrum oralantibiotics with reliable bioavailability
Improved oral agents
higher and more persistent serum andtissue levels
for certain infections as good asparenteral
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Advantages of oral treatment
Eliminates risks of complicationsassociated with intravascular lines
Shorter duration of hospital stay
Savings in nursing time
Savings in overall costs
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Duration of treatment
In most instances the optimumduration is unknown
Duration varies from a single dose tomany months depending on theinfection
Shorter durations, higher doses
For certain infections a minimumduration is recommended
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Recommended minimum
durations of treatmentInfection Minimum duration
Tuberculosis 4 - 6 months
Empyema/lung abscess 4 - 6 weeksEndocarditis 4 weeks
Osteomyelitis 4 weeks
Atypical pneumonia 2 - 3 weeks
Pneumococcal meningitis 7 daysPneumococcal
pneumonia
5 days
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Monitoring efficacy
Early review of response
Routine early review
Increasing or decreasing the level oftreatment depending on response
change route
change dose
change spectrum of antibacterialactivity
stopping antibiotic
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Antimicrobial Resistance:
Key Prevention Strategies
OptimizeUse
Prevent
Transmission
Prevent
Infection
EffectiveDiagnosis& Treatment
PathogenAntimicrobial-ResistantPathogen
AntimicrobialResistance
Antimicrobial Use
Infection
Campaign to Prevent Antimicrobial Resistance in Healthcare Settings
Susceptible Pathogen
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12 Steps to PreventAntimicrobial Resistance
12 Break the chain11 Isolate the pathogen
10 Stop treatment when cured9 Know when to say no to vanco
8 Treat infection, not colonization7 Treat infection, not contamination
6 Use local data5 Practice antimicrobial control
4 Access the experts3 Target the pathogen
2 Get the catheters out1 Vaccinate
Prevent Transmission
Use Antimicrobials Wisely
Diagnose & Treat Effectively
Prevent Infections
Campaign to Prevent Antimicrobial Resistance in Healthcare Settings
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Conclusions
Antibiotic resistance is a majorproblem world-wide
Resistance is inevitable with use No new class of antibiotic introduced
over the last two decades
Appropriate use is the only way ofprolonging the useful life of anantibiotic