Transcript The Rational Use of Antibiotics

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
PK/PD Parameters
Parameters
8
Antibiotic concentration (ug/ml)
Time above MIC :
Proportion of
the dosing
interval when
the drug
concentration
exceeds the
MIC
6
4
Drug A
Drug A
Drug B
Drug B
2
B
B
0
A
Time above MIC
Time
AUC/MIC is the
ratio of the AUC
to MIC
Peak/MIC is the
ratio of the peak
concentration to
MIC
Antibiotic
concentration
Important PK/PD Parameters
Area under the curve
over MIC
PEAK
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
Concentration
dependent killing
Antimicrobials
Goal of therapy
and relevant
PK/PD Parameter
AMGs, Quinolones,
Daptomycin, ketolides,
Macrolides, azithromycin, clindamycin,
streptogramines,tetracyc
lines, glycopeptides,
oxazolidinones
Maximise
concentrations;
AUC/MIC, peak/MIC
Use high doses;
daily dosing for
some agents
Time dependent killing Betalactams
with no persistent
effects
Maximise duration
of exposure; T>MIC
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
Tuberculosis
Empyema/lung abscess
Endocarditis
Osteomyelitis
Atypical pneumonia
Pneumococcal meningitis
Pneumococcal
pneumonia
Minimum duration
4 - 6 months
4 - 6 weeks
4 weeks
4 weeks
2 - 3 weeks
7 days
5 days
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
Pathogen
Antimicrobial-Resistant
Pathogen
Prevent
Infection
Prevent
Transmission
Infection
Antimicrobial
Resistance
Effective
Diagnosis
& Treatment
Optimize
Use
Antimicrobial Use
Campaign to Prevent Antimicrobial Resistance in Healthcare Settings
12 Steps to Prevent
Antimicrobial Resistance
12 Break the chain
Prevent Transmission
11 Isolate the pathogen
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
Prevent Infections
1 Vaccinate
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