rational use of anitibiotic

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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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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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


Drug A

Drug B

B


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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

rational use of anitibiotic

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