Penggunaan antimikroba

yang rasional

Anis Karuniawati
Department of Microbiology,
Medical Faculty-FKUI/RSCM
Founders of the modern era of antibiotics

Alexander Howard Ernst

Fleming Florey Chain

11/18/2019
 Alexander Fleming's
Nobel Prize Lecture

“It is not difficult to make microbes

resistant to penicillin ….

“The time may come when penicillin

can be bought by anyone in the
shops. Then there is the danger
that the ignorant man may easily
under-dose himself and by exposing
his microbes to nonlethal quantities
of the drug make them resistant.”

1929
Timeline of Antibiotic Resistance
 Geographic spread of MRSA

Tong SYC & Kearns AM. Lancet 2013;13:734-34; DeLeo F et al. Lancet 2010;375:1557-1568
 Increasing trends in the rates of Carbapenem Resistant
Organisms
Data from the Taiwan Nosocomial Infection Surveillance system, 2003-2009

S.-H. Tseng et al. Journal of Microbiology, Immunology and Infection (2011) 44, 157e165
Monitoring result of Antibiotics Prescribing at
Primary Health Care Centers, Indonesia

2010 2011 2012 2013

60.00 58.31 58.27

50.00 49.07 47.80 48.00

45.08 44.30
41.28
40.00

30.00

20.00

10.00

0.00
% AB prescribed for Upper % AB prescribed for Non
Respiratory Track Infection specified diarrhoea
7
 0.0
20.0
40.0
60.0
100.0
Gorontalo

80.0 74.7
NTT
NTB
Sulsel
Maluku
Sulut
Sulbar
Sulteng
Sultra
Jabar
Banten
Sumbar
Papua
Jatim
Sumsel
Pabar
Aceh
Malut
Indonesia
86.1

Babel
Sumut
Jateng
Bali
Kaltim
Kep.Riau
Jambi
DKI
Riau
Bengkulu
DIY
Without Prescription per Provinces

Kalbar
National Health Survey, 2013

Kalsel
Lampung
Proportion of Households Storing Antibiotics

Kalteng
93.4
Antibiotics: End of The Road?
 Global Action Plan against AMR: 2015
5 Strategic Objectives

1. Improve awareness and understanding of AMR through effective

communication, education and training.
2. Strengthen the knowledge and evidence base through research
and surveillance.
3. Reduce the incidence of infection through effective hygiene and
infection prevention measures.
4. Optimize the use of antimicrobial medicines in human and
animal health.
5. Develop the economic case for sustainable investment that takes
account of the needs of all countries, as well as the case for
investment in new medicines, diagnostic tools, vaccines and other
interventions.
We the health ministers…..
Regional Strategy on AMR and
Resolution of RC63

Goal: To minimise the

morbidity and mortality due
to antimicrobial resistant
infection and to preserve the
effectiveness of antimicrobial
agents in the treatment and
prevention of microbial
infections.
(simplified version of global
strategy)
 Role of Professional Bodies

• Developing guidelines

• Guidelines refer to specific

treatment of individual diseases
(therapy) or prophylaxis

• Professional bodies in
microbiology can play a leading
role in developing antibiotic
guidelines

• Ownership by all is required to

put these into practice
 Komite Pengendalian Resistensi
Antibiotik, Kemenkes RI

Dr. Hari
Parathon
Dr. Muchlis Dr. Kie
Dr. Masfar Dr. Anis Chen
Dr. Purnamawati

Prof. Djoko Widodo

Dr. Zunilda
Prof. Taralan Bu Qibty
 Strategic Plan of AMR Control in Indonesia 2015-2019

Increasing Public Health quality through

OUTCOME AMR Control Program
(Diagnostic, Antibiotik usage, Infection management, AMR Spreading,
Decreasing AMR Incidence )

Realization of Community Care toward AMR Global Update of AMR Collaboration

To Develop AMR Control Implementation in teaching material
Problem and control between Ministry of
Health Facilities ( in Health
(% understanding of AMR, % antibiotic consumption,% health, ministry of
( % number of Health Facility included) education Agriculture and
decreasing antibiotic OTC))
OUTPUT

(Medical Doctor, vetenerary, ministry of

Pharmacetical, education
Nurse, Midwife)
STRATEGIC IMPLEMENTATION PROCES

Realization Realization of

Avaibility of AMR control Program funds

Realization Realization
of AMR education Realization Realization

Implementation of AMR surveillance

Realization of AMR of AMR
Control system of antibiotic of
of AMR Control in Control in
collaboration of AMR selling collaboration
Control in Primary Private
within Problem and control and between gov.
Hospital Health Practice
profesional control in monitoring and NGO
Facilities setting
organization community
Collaborat
Collaboratio
ion of
Collaborati Collaborati n between
ministry of
on among on of institution
agriculture
Realization of AMR Information system base on Realization of AMR Information system base health medical that
and
health facilities on community setting faculty / profession concern in
vetenerer
university collegium antibiotic
y
use
Existing system of AMR control in Health facilities and community
SUMBER DAYA
KESEHATAN

Avalaible competent health provider in for Facilities support for AMR Control
AMR conrtol program: Gov. Regulation support
(Phycisian, Clinical Microbiologist, Clinical
program :
(National Policy, National
pharmacist, Clinical Pharmacologist, ICN) (Diagnostic, IC, Pharmaceutical
guideline, Clinical guideline)
fascilities)

17
 Infectious Diseases Expert Resources

Infectious Diseases
Specialists
Healthcare Infection Control
Epidemiologists Professionals

Clinical Optimal
Pharmacists Patient Care

Clinical Clinical
Microbiologists Pharmacologists
Surgical Infection
Experts
Campaign to Prevent Antimicrobial Resistance in Healthcare Settings, CDC
 Inappropriate Prescribing: Why?

• Lack of awareness
• Prescription purely on demand by the patients
(lack of doctor-patient communication)
• Knowledge of antibiotic usage
• Infectious diseases involve multiple organ system
need integrated patient management
• Antibiotic Guideline is not available
• Antibiotic Guideline is available, but:
– not based on local data
– for common conditions in different settings
– over-reliance on guidelines
 The Use of Antibiotics

• Prophylaxis
– Medical
– Surgical

• Therapy:
– Empiric: before microbiological confirmed
– Definitive: after microbiological confirmed
 Prescribing

• do not copy the prescribing behavior of your

clinical teachers, or existing standard
treatment guidelines, without explanation
“why certain treatments are chosen”

• bad prescribing habits lead

– ineffective and unsafe treatment
– exacerbation or prolongation of illness
– distress and harm to the patient
– higher costs
Guide to Good Prescribing. WHO
 Steps in Prescribing

i. Define the diagnosis

ii. Specify the therapeutic objective
iii. Make an inventory of effective groups of
drugs
iv. Choose an effective group according to
criteria
v. Choose a P-drug
P-drugs are the drugs you have chosen to prescribe
regularly, and with which you have become familiar. They
are your priority choice for given indications.
Guide to Good Prescribing. WHO
 Diagnosis

• Infectious disease?

• The possible cause?

Epidemiology, Local pattern
Bacteria?
Which?  body site

Other microbes?
 Antibiotic Prescribing

AIMED Model
Intensive Care Unit Empirical Antimicrobial Treatment Guidelines. New South Wales. 2010
 Antibiotics Selection

• Efficacy
• Safety
• Suitability
• Cost
• “Availability”
 Antibiotic Choices:
Likely Infecting Pathogens

Solomkin JD, et al. Clin Inf Dis. 2003;37:997-1005

Niedermen MS, et al. Am J Respir Crit Care Med. 2005;171:388-416
Stevens DL, et al. Clin Inf Dis. 2005;41:1373-406
 Empirical Antibiotic Therapy

• spectrum of microorganisms to be covered

• should be based on
– severity of the infection
– any available epidemiological data of the
bacteria pattern and its susceptibility
– results or current Gram-stained smear findings

• duration of treatment: 3-5 days

 Empirical Antibiotic Therapy

• Mild-moderate
– relatively narrow spectrum

• severe infections/more-extensive, chronic

moderate infections:
– broad-spectrum agent: have activity against
gram-positive cocci , gram-negative and (if
necessary) anaerobic
 Day 3 Assessment of an AB Care

• Was there an AB plan? (name, dose,

route, interval of administration, planned
duration)
• Was there a review of the diagnosis?
• If positive microbiological results were
available, was there any adaptation of AB
treatment? Streamlining/discontinuation
• Documentation of any changes
 Eradication of organisms

• The antibiotic must bind to its target site(s) in the bacterium

– Penetrate the outer membrane
– Avoid being pumped out of the membrane
– Remain intact as a molecule (eg, avoid hydrolysis of ß-
lactamase)

• Antibiotics must occupy an adequate number of binding sites 

related to its concentration within the microorganism

• Antibiotic should remain at the binding site for a sufficient

period to adequately inhibit the metabolic processes of the
bacterium
 Antimicrobials Pattern

1.Concentration Dependent
Antibiotics

2.Time Dependent Antibiotics

3.Persistent Effect
 Pattern of Activity Antibiotics Goal of Therapy PK/PD Parameter

Type I Aminoglycosides Maximize 24h-AUC/MIC

Concentration-dependent killing Daptomycin concentrations Peak/MIC
and Fluoroquinolones
Prolonged persistent effects Ketolides

Type II Carbapenems Maximize duration T>MIC

Time-dependent killing and Cephalosporins of exposure
Minimal persistent effects Erythromycin
Linezolid
Penicillins
Type III Azithromycin Maximize amount 24h-AUC/MIC
Time-dependent killing and Clindamycin of drug
Moderate to prolonged persistent Oxazolidinones
effects. Tetracyclines
Vancomycin
 Other PD Concepts

• Volume of distribution
• Clearance
The intrinsic ability of the body to remove drug
• Half-life and steady state
The longer the T½ of a drug, the longer it takes to
achieve a steady state-concentration
• Post antibiotic effect
The persistent suppression of bacterial growth after
exposure of a microorganism to an antibiotic
• Bioavaibility
Degree of absorption of an antibiotic
Interpretasi Hasil Uji Kepekaan Antibiotik

• Mengenali hasil yang tidak biasa

• Kenali bakteri yang memiliki kemungkinan

sifat intrinsik resisten terhadap jenis
antibiotik tertentu

• Antibiotik sebagai indikator

DM.Livermore, TG Winstanley, KP Shannon. J.of
Antimicrobial Chemotherapy (2001) 48, Suppl.S1
 Mengenali hasil resisten yang tidak biasa
(Exceptional Resistance Phenotypes)
• Sifat resisten secara fenotip beberapa spesies bakteri terhadap antibiotika
yang hampir tidak pernah atau sangat jarang ditemukan.

• Hasil resisten kemungkinan karena:

– Kesalahan identifikasi
– Kesalahan AST

• Jika resistenkirimkan isolat ke Lab Rujukan (konfirmasi)

• Exceptional Resitence Phenotype dapat berubah seiring waktu

• Terdapat kemungkinan perbedaan secara Regional, maupun Nasional, bahkan

antar Rumah Sakit
Mengenali hasil resisten yang tidak biasa
(Exceptional Resistance Phenotypes)
 Resisten Intrinsik
• kemampuan alamiah dari spesies bakteri untuk bertahan
terhadap antimikroba tertentu melalui struktur atau fungsi
yang diturunkan, sehingga menyebabkan toleran terhadap
golongan antibiotik tertentu (=insensitivity)

• Penyebab:
 Berkurangnya ikatan Antibiotik pada target bakteri
 Antibiotik tidak mampu masuk ke dalam sel bakteri
 Pengeluaran antibiotika oleh sistem efflux aktif yang di kode oleh kromosom
 Bakteri memproduksi enzim yang dapat menginaktifasi obat

http://amrls.cvm.msu.edu/microbiology/molecular-basis-for-antimicrobial
 Resisten Intrinsik

• Aktifitas antimikroba tertentu menjadi tidak efektif pada spesies

tertentu

• Sebaiknya tidak diujikan secara in vitro

• Walaupun secara in vitro ditemukan susceptiblekemungkinan

kesalahan teknisjangan digunakan

• Jika tidak ada pilihan antimikroba lain  mungkin bisa

dipertimbangkan untuk digunakan sebagai pilihan terapi
(komunikasi antara klinisi dan SpMK)
Leclercq et al. EUCAST expert rules in antimicrobial susceptibility testing. Clin Microbiol Infect. 2011.
Antibiotik sebagai indikator resisten

Contoh
• MRSA: resisten thd semua β-lactams

• ESBL (ceftazidime, cefpodoxime, cefotaxime,

ceftriaxone): hindari semua cephalosporin

• N.gonorrhoeae (nalidixic acid): indikasi

penurunan kepekaan terhadap
fluoroquinolones
 Antibiotic Stewardship

A process to assist and support clinician with

decision regarding the optimal selection, dose
and duration of an antimicrobial agent  to
ensure the best clinical outcome for the
treatment or prevention of infection, with:
 minimal toxicity to the patient
 minimal impact on subsequent resistance
development
 Decrease drug acquisition costs
 Antibiotic Stewardship

• Ensure prudent, effective, appropriate, safe, and

(ideally) evidence-based antimicrobial use

• It may encompass features including:

– Education
– Feedback
– Restriction
– Electronic prescribing systems
 Benefits of AM Stewardship

• Improve clinical care by ensuring that the most appropriate

antimicrobial agents are given for the appropriate duration by
the appropriate route

• Reduce pressure for the emergence and spread of multiply

resistant organisms due to inappropriate broad spectrum
antimicrobial use

• Reduce drug acquisition costs

• Better education of prescribers, and encouragement for units to develop

and submit evidence-based antimicrobial use protocols
 Two Core AMS Strategies

• Prospective audit of AB use with

intervention and feedback to the prescriber

• Formulary restriction and preauthorization

requirements for specific agents

Dellit TH, et al. Clin Inf Dis. 2007;44:159-77

Jacob JT, et al. Expert Rev Anti Infect The, 2010;893-902
Classification of AB
Evaluation by Gyssens

I: Agree with the use of AM

II: AB prescription is inappropriate due to
– Improper dosage, dosage interval, route
III: AB prescription is inappropriate due to
– Excessive length or duration to short
IV: AB prescription is inappropriate due to
– More effective alternative
– Less toxic alternative
– Less expensive alternative
– Less broad spectrum alternative
V: AB prescription is unjustified
VI: information insufficient for categorization
Efforts to Control Resistance

Develop New
Drugs and
Vaccines
Improved
Diagnostics
Reduce
Resistance
Reservoirs
Antimicrobial
Stewardship
Infection
Control

Research &
Public Policy
Education
Efforts to Control Resistance

Develop New
Drugs and
Vaccines
Improved
Reduce Diagnostics
Resistance
Reservoirs

Antimicrobial
Stewardship
Infection
Control
Research &
Public
Policy
Education
Antibiotics are
a precious
resource
We need to
preserve this
resource by
working together