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Rational Usage of

Antibiotics
Prudential Use of Antibiotic in Adult

dr. Rizky
Perdana,SpPD,KPTI,FINASIM

Division of Tropical and Infectious Diseases


Department of Internal Medicine
Faculty of Medicine University of Sriwijaya
Moh. Hoesin Hospital

Apa itu Prudential Use of


Antibiotic in Adult ???
Untuk memahami nya, mari kita
simak kasus-kasus pada slide berikut
ini
Silahkan baca baik-baik

Facta di Klinik

Curhat pasien tentang


antibiotika
"Kira kira 2 bulan yang lalu saya sakit tenggorokan. Lalu
saya ke dokter umum diberi antibiotik Fixef 100 untuk 4
hari (8 biji). Setelah abis, tenggorok masih sakit saya ke
dokter umum yang lain lagi dan mendapat volequin
untuk 5 hari dan ternyata tidak juga hilang, masih saja
terasa sakit terutama menelan. Saya kembali ke dokter
umum pertama, dan mendapat Mezatrin selama 3 hari.
Lagi2 juga masih sakit setelah Mezatrinnya abis. Saya
pindahke dokter lain dan diberi Capsinat 500 untuk 5
hari (15 biji). Setelah obat itu abis ternyata masih aja
sakit lagi

Akhirnya saya ke THT. Kali ini obatnya Claneksi 500 (15


biji) untuk 5 hari, setelah abis lagi-lagi masih sakit dikit,
ditambah lagi Claneksi 500 (15 biji) untuk 5 hari lagi. Terus
sakitnya sudah banyak berkurang saya kembali lagi dan
dokter THT melihat masih ada merah dikit terus ditambah
lagi Claneksi 500 (10 biji). Selain antibiotik ada juga obat2
anti alergi dan anti radang.
Bersamaan dengan habisnya obat itu saya harus
menjalani laparoskopi diagnostik untuk kandungan. Terus
dokter kandungan memberi Claneksi 500 lagi 15 biji lagi.
Waktu itu tenggorokan saya juga luka akibat selang bius
sehingga sakit buat nelan. Jadi total saya menghabiskan
Claneksi 500 sebanyak 55 biji dalam waktu sekitar 20 hari.

Tetapi setelah obat habis beberapa hari kemudian


sakitnya muncul lagi Dok..
Malah setelah 2 minggu saya minum obat itu kok malah
merasakan sering sakit perut bagian bawah dan saya
pun sering mengalami diare. Saat ini saya tidak hanya
mengalami sakit tenggorok yang tidak kunjung reda,
malah sakit saya bertambah lagi seperti perut saya
sering kram dan diare. Apakah ini efek samping obat
antibiotik yang saya minum itu? dan apakah saya
sudah kebal dengan antibiotik? Bolehkah minum
antibiotik jangka panjang seperti saya itu? Saya takut
pergi ke dokter lagi untuk sakit perut dan diare yang
saya alami karena pasti mendapat antibiotika lagi.
Mohon sarannya dok. Terima kasih

Antibiotic Resistance
A worldwide problem1
Associated with
increased morbidity,
mortality, and
hospital costs1
Occurs in both
hospitals and the
community2
1: R. A. Kulkarni et al. Indian J Surg. 2005: Volume 67(6): 308-315.
2 Ben-David D, Rubenstein E. Curr Opin Infect Dis 2002;15:151-156.

Current Problems of
Bacterial Resistance
Policy & Advocacy of IDSA; July 2004
B AD B UGS , N O D RUGS
As Antibiotic Discovery Stagnates A Public Health Crisis
Brews

Native
Organisms

Perl TM. Gram Negative Bacterial Resistance in Healthcare: The Brave New World Healthcare

Campaign to Prevent Antimicrobial Resistance in Healthcare Settings

Antimicrobial Resistance:

Key Prevention Strategies


Pathogen
Antimicrobial-Resistant
Pathogen
Susceptible
Pathogen
Prevent
Infection

Prevent
Transmission

Infection

Antimicrobial
Resistance

Effective
Diagnosis
& Treatment

Optimize &
Rational
Use

Antimicrobial Use

Consideration When Choosing


an Antibacterial Agent
Outcome

Microbiology
Antibacterial spectrum

Drug
PK
Absorption
Distribution
Metabolism
Excretion
Optimal dosing
regimen

(Scaglione,
2002)

Clinical efficacy
Bacterial eradication
Compliance with
dosing regimen
Tolerability
Rate of resolution
Prevention of resistance

Mechanism of action

Concentration
at infection site

Pathogen MIC
PD

Time vs. concentration


dependent killing
Bactericidal vs. bacteriostatic
activity
Tissue penetration
Persistence of antibacterial effect

Rational Antimicrobial
Therapy
Clinician

Drug

Patient

Microorganism
Microbiologist

Factors in Choices of Antibiotics:


Drug Interactions
IV fluids:
incompatible
drug mixtures

Kidney:
Effect on passive
readsorbtion &
active secretion

Bowel:
Other drug or food
modifies absorbtion

Drug interaction

Plasma:
Competitition for
protein binding
sites

Liver:
Receptor sites:
Induction of liver enzymes -Drugs may compete
modified excretion
at binding site

Examples of
Antibiotics-Drugs Interactions
Site

Antimicrobial Interacting drug/effects

IV fluids

Many

Many - Do not mix IV fluids

GI tract

Tetracyclines
Quinolones

Absorbtion by food
Absorbtion reduced by iron

Warfarin (antiocoagulant), SulphoProtein bindingChloramphenicol


Co-trimoxazole ureas effects
Liver enzyme Rifampicin
induction
Kidney

Aminoglycosides

Oral contraceptive, warfarin, antidia


betics, cyclosporin, etc, metabolism
, i.e., effect
Loop diuretics (frusemide)
ototoxicity

Antibiotic Usage in
Clinical Practice

Step in Infectious Diseases


Management
Microbiological specimen

Microbiological result

Empirical Initial Antibiotics


Depends on :
Presumed site of infection
Suspected or known pathogens
Grams stain results
Previously have been documented to colonize
or infect the patient
Local resistance patterns
Limited spectrum of antibiotics available
Allergies
Cost
Host factor

Who is the Host ?


1. Immunocompetence
2. Immunodeficiency / immunocompromized
:
Neutropenia
Indwelling medical devices
Hospitalized patients, esp. ICU patients
Neoplasm
Corticosteroid/ Cytotoxic agent
Burn
Diabetes
Trauma
Drugs user, Alcoholic
Elderly, neonatal, pregnancy and

Factors Involved in
Optimal Initial Antibiotic
Therapy

Increased

Antimicrobial Combination:
When we need?
Unknown focus of infection
Polymicrobial infection, eg: abscess caused
by multiple aerob and anaerob organisms
Decrease resistance rate, eg: Tb treatment
Decrease dose related toxicity
Increase antimicrobial potency

Chambers HF. Antimicrobial agents. 2001

Strategy for Empirical


Treatment
Patien
t
Hospitaliz
ed

Outpatie
nt
Stable
condition
Escalatio
n

Severe/ high
risk
Deescalation

Antibiotic selection based on


susceptibility and resistance pattern,
immunity status, comorbidity,
organ dysfunction
Pohan HT, 2005

Antibiotic monotherapy or
combination

Choosing The Right Strategy


Escalation: not life threatening infection
De-escalation:

Ventilator-associated pneumonia
Nosocomial pneumonia
Blood stream infection
Severe community-acquired pneumonia
Meningitis
Sepsis
ICU patient

De-escalation Approach to
Antimicrobial Utilization
Obtain appropriate microbial sample
for culture and special stain

Follow up: temp, WBC, CXR, PaO2/FiO2,


haemodynamic, organ function

Search for
superinfection,
abscess
formation,
non-infectious
caused of
fever

No
Yes

Kollef, Drugs 2003;63 (20): 2157

Antibiotics in De-escalation:
Combining Rapid and Appropriate

iv antibiotics as early as possible, within the


first hour
Broadspectrum active against likely
bacterial/fungal pathogens, good penetration
into presumed source
Reassess antimicrobial regimens daily
Combination therapy should be considered in
Pseudomonas infections, neutropenic patients
de-escalate
Stop antimicrobial therapy if cause is found to
be non-infectious

Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al. Crit Care Med 2008; 36(1): 296-327

Kumar A. et.al. Crit Care Med 2006;34:1589-96

Impact of the appropriateness of antibiotics


therapy on mortality of Gram-negative
bacteremia
NS

P<0.001
P<0.001

P<0.001

Bochud PY. Intensive Care Med 2001;27:s33-8

De-escalation Approach to
Antimicrobial Utilization
Obtain appropriate microbial sample
for culture and special stain

Follow up: temp, WBC, CXR, PaO2/FiO2,


haemodynamic, organ function

Search for
superinfection,
abscess
formation,
non-infectious
caused of
fever

No
Yes

Kollef, Drugs 2003;63 (20): 2157

Antimicrobial Treatment based on


Microbiological Culture Results
Microbiological culture results

Colonization
No treat

Optimized

Pathogen
Sensitive

Resistant

Treat with

Antibiotics

Recommended
Antibiotics

Combination

PKPD

Strategy in Managing MDR


Treat pathogen not colonization
Based on local susceptibility data
Monotherapy or combination
Optimalization PK/PD
Considered comorbidities, organ
function
Prevent transmission

Control of Antibiotic Usage


Avoid antibiotic homogeneity
Promote appropriate use of multiple drug
class
Apply formulary control and restrict of
specific agent or drug class that resistant
Consider antibiotic cycling, rotation or
mixed use of antibiotic classes
Develop and promote antibiotic guidelines
and protocol based on local data

Antibiotic Policy
Classification of antibiotics
Class A : Not restricted
Class B : Not restricted, under
supervision
Class C : Restricted
Implementation
Evaluation and surveillance
Auditing

Classification of Antibiotics
Class A
Aminoglicoside
Penicillin
Cephalosporin
gen.I,II
Chloramphenicol
Fucidic acid
Lincosamide
Macrolide
Nitroimidazol
Fluoroquinolone
gen.I,II
Tetracyline
TMP-SMX
Fosfomicin
Polypeptide

Class B
Cephalosporin
e
gen III
Fluoroquinolo
ne
gen III-IV
Ertapenem

Vancomycin

Class C
Teicoplanin
Linezolide
Cefepime
Cefpirome
Ceftazidime
Pip-Tazo
Carbapenem
Tygecicline

Implementation of
Antimicrobial Policy in Hospital
Outpatient

Community

Hospital

Class A

Class A

Class B

Class C

Class B/C

Class C

Inpatient
WAR
D
ICU

Mild
Moderat
e Severe

Evaluation and Surveillance


1

Evaluate the quantity of


antibiotic usage

Retrospectively from the medical


record
From medical prescription

Evaluate the quality of antibiotic


usage

Using classification by Gyssens

Evaluation category of
Antibiotics Usage by Gyssens
I.
II.

Correct Usage
Incorrect due to:
a) Incorrect dose b) Incorrect interval c) Incorrect route

III.

Incorrect due to:


a) duration too long b) duration too short

IV.

Incorrect due to: Alternative drug that is


a) more effective b) less toxic c) cheaper d) more specific

V.
VI.

No Indication
Medical record is insufficient to be
evaluated

Evaluation and Surveillance


Surveillance of every inpatient ward,
intensive care ward, and surgery
room periodically, e.g. monthly
surveillance in internal medicine
ward
Report of surveillance periodically,
e.g. report of surveillance in internal
medicine ward every 6 months

Auditing
Periodically done by antibiotic team
(multi department), commissioned
by management of hospital
Audit of medical records, copy of
prescriptions
Percentage of compliance to
antibiotic guideline
Reward and punishment

Conclusions
Types of antibiotic usage: empirical,
definite, prophylaxis, pre-emptive
Rational antibiotic therapy: rapid,
appropriate, cost effective
The implementation of antibiotic policy to
promote:
rational use of antibiotics,
cost-effective therapy,
prevent collateral damage