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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
AT
ION
AL
RA
TIO
NA
L
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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