Dr. NAFRIALDI, PhD, SpPD, SpFK

Lahir: Bukittinggi, 30 Oktober 1961.

Pendidikan

Dokter Umum: FKUI, 1986

S2 Farmakologi: Universite Claude Bernard, Lyon, Perancis, 1991

S3 Farmakologi: Universite Montpellier, Perancis, 1994

Spesialis Penyakit Dalam: FKUI, 2005

Pekerjaan

Staf Pengajar Departemen Farmakologi FKUI

Deputy Chief Editor Medical Journal of Indonesia

Editorial Board Member, Acta Medica Indonesiana

Sekretaris Komite Etik Penelitian FKUI-RSCM 1

Principles of Rational Antibiotic Use

Dr. NAFRIALDI, SpPD, PhD, SpFK

Departemen Farmakologi FKUI, Jakarta

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Antibiotics are the most important weapons for the treatment of many infectious diseases caused by bacteria.

However, irrational use will lead to: Selection of drug resistant organism Interference of normal flora Increased incidence of side effects Increased cost

Introduction

Rational Use of Medicine

Patients receive medications:

appropriate to their clinical needs

INDICATION,

in doses that meet their own individual requirements proper DOSAGE,

for an adequate period of time proper

DURATION,

and at the lowest cost to them and their community

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Rational Use of Antibiotic

Proper Indication

Proper dosage

Proper duration

Lowest cost

Other considerations:

Proper drug choice

Proper route of administration

Proper timing of administration

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There is no clear cut between rational and irrational drug use

IRR

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TIO

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Using AB without clear indication

AB for viral infection (mumps, faringitis, acute diarrhea, dengue fever)

Reliance of AB use on laboratory results, without adequate clinical background:

AB use based on Widal test

AB use for reactive leukocytosis (colic pain, MCI, stroke)

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Exemples of Irrational AB Use

Neglecting other factors

Foreign body, pus, necrotic tissue

AB combinations or broad spectra as a cover for diagnostic imprecision

Inappropriate AB combination

Early AB treatment for FUO

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Exemples of Irrational AB use

Types of AB use

Empirical

Without microbiolgic data

Definitive

Based on culture and sensitivity test

Prophylaxis:

Surgical

Non surgical

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Empirical AB Use

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Use of AB without microbiology and sensitivity data

The most commonly used

The most common misused

Needs local updated sensitivity pattern

Important in severe condition Live saving

AB combination may be needed

It is important to take culture specimen before AB administration.

1. Is an AB really indicated?

2. What is the most appropriate AB?

3. What dose, frequency, route and duration ?

4. What is the aim of AB treatment ?

Empirical, definitive, prophylaxis

5. When to use antibiotic combination

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Considerations in Using AB

Antibiotic is useful only for the treatment of bacterial infections

Fever is commonly use as indicator Not all fevers are due to infection Not all infections are due to bacteria Not all bacterial infections require

antibiotics In patients with viral infection, there is

no evidence that AB will prevent secondary infection

1. Is an AB really indicated?

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Depends on: Etiologic agent Identification Sensitivity

Patient factors Immune status Comorbid, organ dysfunction

Drug factors PK-PD

2. What is the most appropriate AB?

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Etiologic Agent

What organism are most likely ? Gram staining may give rapid clue Bacterial culture should give definitive answer

What organ system involve URTI: mostly gram positive Pulmonary: H. influenzae, S. pneumoniae Skin, cellulitis: mostly gram positive Urinary and GI: usually gram negative

Hospital or Community acquired ? Hospital acquired: gram negative, MRSA, VRE,

pseudomonas, highly resistant microbe

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Importance of local 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

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Etiologic Agent

Laboratory results

Was the specimen properly collected ?

How to interpret the result?

The isolated microbial is not necessarily the causative pathogen

Is it a contaminant/coloniser or is it the causative agent?

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Etiologic Agent

Physiological factors

Age: Neonates, children,young adult, elderly

Immune status

Immuno competent

Immuno compromized: DM, HIV, long-term steroid treatments

Comorbid

liver disease, kidney dysfunction

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Patient factors

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Other factors

Local factors may affect the AB activity

Pus, can bind drugs or inhibit drug action

Low pH in infected sites and anaerobic condition

Foreign body

Prosthetic materials promotes a bacterial biofilm favor bacterial persistence

frequent relapses

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3. What dose, frequency, route and

duration ?

Depends on:

PK-PD of AB

Killing pattern

Concentration dependent

Time dependent

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Pharmacokinetic-Pharmacodynamic

(PK-PD) Parameters

MIC

Time

CONC. Cmax

Area Under the Curve

Time above MIC

• Concentration-dependent killing

Cmax/MIC required > 10 x

•Time-dependent killing

Time above MIC required: > 40%

Concentration-dependent killing High Cmax/MIC ratio is important

High single dose may be better than

devided doses

Exp: aminoglycoside, quinolones

Time-dependent killing Duration of exposure (T > MIC and

AUC24/MIC ratio) are important

Prolonged infusion is better

Exp: penicillins, cephalosporins21

Killing patterns of AB

Antimicrobial Combination

Aims:

To have synergistic effect in specific infection (endocarditis, Ps aeruginosa, H influenzae).

To retard the emergence of resistant microorganism (in TB, H. pylori infection)

Indications

Empirical therapy in severe infection HAP due to P. aeruginosa

Meningitis

Febrile neutropenia, sepsis

Intra-abdominal abcess

Polymicrobial infection22

Considerations in AB combination

Different mechanisms of action B-lactam + aminoglycoside B-lactam + macrolide or quinolone

Different spectrum (gr+, gr -, anaerobic) Sinergistic AB combination may have additive toxicity

(Vanco + aminoglycoside) Avoid long-term combination for empirical

treatment Be cost sensitive

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Etiologic Agent

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Disadvantages of AB Combination

Increase risk of toxicity

Selection of multiple-drug resistant microorganisms

Eradication of normal host flora with subsequent superinfection

Increase cost to patients

Possibility of antagonistic effect

AB PROPHYLAXIS

Non-surgical Streptococcal infection in patient with a history

of RHD

Before dental extraction in patients with implanted prosthetic devices

Prophylaxis of TB, PCP, in HIV-infected patients

In patients with viral infection, there is no evidence that AB will prevent secondary infection

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AB prophylaxis

Surgical Clean-contaminated prophylaxis

Contaminated treatment

Selected surgical cases (cardiac, ophtalmic, brain) prophylaxis

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AB prophylaxis

Use 1st or 2nd generation cepalosporins.

If anaerobic bacteria is suspected, metronidazole may be added

The use of 3rd and 4th generation cephalosporin, carbapenem, and quinolones, is not recomanded.

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Surgical AB Prophylaxis

AB must be present at wound site at the time of its closure

The drug must be given IV within 30-60 minutes before incision

Another one dose for prolong procedure (> 3h) or if bleeding > 1500 ml.

The AB must be active against the most likely contaminating microorganisms

Use beyond 24 hour is unnecessary

GYSSEN CRITERIA FOR QUALITY of AB USE

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Gyssen’s algorythm

Gyssens’ category for Quality of AB Use

VI. Insufficient information stop

V. Unjustified Indication stop

IV. Inappropriate AB choice due to availability of: More effective alternative (IV a)

Less toxic alternative (IV b)

Less expensive alternative (IV c)

Narrower spectrumalternative (IV d)

III. Inappropriate duration (too long (IIIa); too

short (IIIb)

II. Improper dosage (IIa), interval (IIb), route (IIc)

I. Improper timing

0. Appropriate use of AB therapy/prophylaxis 31

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