1. The Rational Use of Antibiotics
Victor Lim
International Medical University
Kuala Lumpur, Malaysia

2. 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

3. 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

4. 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

5. Prescribing an antibiotic
Is an antibiotic necessary ?
What is the most appropriate antibiotic ?
What dose, frequency, route and duration ?
Is the treatment effective ?

6. 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

7. Arroll and Kenealy, Antibiotics for the common cold
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.

8. Is an antibiotic necessary ?
Not all bacterial infections require antibiotics
Consider other options :
antiseptics
surgery

9. Choice of an antibiotic
Aetiological agent
Patient factors
Antibiotic factors

10. The aetiological agent
Clinical diagnosis
clinical acumen
the most likely site/source of infection
the most likely pathogens
empirical therapy
universal data
local data

11. 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

12. 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

13. Patient factors Age Physiological functions Genetic factors Pregnancy
Site and severity of infection
Allergy

14. 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

15. 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

16. Antibiotic concentration (ug/ml)
Important PK/PD Parameters
Important PK/PD Parameters
Time above MIC : Proportion of the dosing interval when the drug concentration exceeds the MIC 8 6
Drug A
Drug A 4
Drug B
Drug B
Antibiotic concentration (ug/ml) 2 B B A
Time
Time above MIC

17. Area under the curve over MIC Antibiotic concentration
Important PK/PD Parameters
Area under the curve over MIC
AUC/MIC is the ratio of the AUC to MIC
Peak/MIC is the ratio of the peak concentration to MIC
PEAK
Antibiotic concentration
MIC
Time

18. 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

19. Goal of therapy and relevant PK/PD Parameter
Goal of therapy based on PK/PD
Pattern of Activity
Antimicrobials
Goal of therapy and relevant PK/PD Parameter
Concentration dependent killing
AMGs, Quinolones, Daptomycin, ketolides, Macrolides, azithro-mycin, clindamycin, streptogramines,tetracyclines, glycopeptides, oxazolidinones
Maximise concentrations; AUC/MIC, peak/MIC
Use high doses; daily dosing for some agents
Time dependent killing with no persistent effects
Betalactams
Maximise duration of exposure; T>MIC
Use more frequent dosing; longer infusion times including continuous infusion

20. 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

21. 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

22. 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

23. 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

24. Recommended minimum durations of treatment

25. 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

26. Antimicrobial-Resistant Pathogen Antimicrobial Resistance
Campaign to Prevent Antimicrobial Resistance in Healthcare Settings
Antimicrobial Resistance: Key Prevention Strategies
Susceptible Pathogen
Antimicrobial-Resistant Pathogen
Pathogen
Infection
Prevent Transmission
Prevent
Infection
Antimicrobial Use
Antimicrobial Resistance
Effective
Diagnosis
& Treatment
Optimize Use

27. 12 Steps to Prevent Antimicrobial Resistance
Campaign to Prevent Antimicrobial Resistance in Healthcare Settings
12 Steps to Prevent Antimicrobial Resistance
12 Break the chain
11 Isolate the pathogen
10 Stop treatment when cured
9 Know when to say “no” to vanco
8 Treat infection, not colonization
7 Treat infection, not contamination
6 Use local data
5 Practice antimicrobial control
4 Access the experts
3 Target the pathogen
2 Get the catheters out
1 Vaccinate
Prevent Transmission
Use Antimicrobials Wisely
Diagnose & Treat Effectively
Prevent Infections

28. 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