Implementing Antibiogram and

Antimicrobial Stewardship in Hospital

Tri Wibawa
Department of Microbiology
Faculty of Medicine – Public Health & Nursing
Universitas Gadjah Mada
 AMR: An increasing global threat
requiring global action
• Not a new issue, several previous
initiatives
• Increasingly a global threat to public
health
• Untreatable infections; multiple-drug
resistance
• Desperation over "dry pipeline"
• Growing awareness and commitment
• Political, professional, public
• Global problem requiring a global solution
Growing Awareness & Political
Commitment
Deaths attributable to AMR every year by 2050
Mortality & Economic
impact
• By 2050, lead to 10 million
deaths/year
• Reduction of 2 to 3.5 percent in
GDP
• Costing the world up to $100
trillion

J. O'Neil, 2014. Antimicrobial Resistance: Tackling a crisis for the health and wealth of nations.
Robin McKie
Sunday 8
October
2017
05.59 BST

• “Scientists attending a recent meeting of the American

Society for Microbiology reported they had uncovered a
highly disturbing trend. They revealed that bacteria
containing a gene known as mcr-1 – which confers
resistance to the antibiotic colistin – had spread round the
world at an alarming rate since its original discovery 18
months earlier. In one area of China, it was found that 25%
of hospital patients now carried the gene.”
Genetics Aspects of AMR
• Intrinsics
• Acquired
• Exogenous gene:
• Plasmid
• Transposon
• Integron
• Bakteriophages
• Mutation
• Spontan (growth-dependent mutations)
• Hypermutable
• Adaptive mutagenesis
• Horizontal gene trasfer: conjugation, transduction, transformation
• Combination of various mechanisms
 Bakteri secara random mengalami
Mutasi → resisten terhadap AB
Model
•Terapi tidak efektif
Penularan Seleksi •Non-compliance

Bakteri
Resisten Penularan

Bakteri Mutan tumbuh Bakteri Mutan tumbuh

Di dalam host pertama Pada host berikutnya
• the development of
colistin-dependent
and -resistant
mutants from the
colistin-susceptible
wild-type (WT)
strain, H08-391 of
Acinetobacter
baumannii.

(Lee et al., 2017;

www.nature.com/scientificr
eports)
Prevalence of ESBL in 6 Referal Hospital (Jan – Oct 2013)
 Antibiotics Susceptibility Pattern
Dr. Soeradji Tirtonegoro Hospital (1st Sem 2017)
Gram (+) Gram (-)
Antibiotics isolates %S %R 95%C.I. Antibiotics Isolates %S %R 95%C.I.
Penicillin G 95 20 70.3-87.2 Ampicillin 306 8.5 87.7-94.3
Ampicillin 22 95.5 0.2-24.8 Amoxicillin/Clavulanic acid 289 49.1 45.0-56.8
Cefazolin 2 100 0.0-80.2 Ampicillin/Sulbactam 49 75.5 13.8-39.2
Ceftriaxone 5 100 0.0-53.7 Piperacillin/Tazobactam 448 84.2 12.6-19.6
Cefotaxime 4 100 0.0-60.4 Cefazolin 284 26.4 68.0-78.6
Cefoxitin 75 80 12.0-31.1 Cefuroxime 307 45.3 48.9-60.3
Gentamicin 9 22.2 40.2-96.1 Ceftazidime 148 60.1 32.0-48.3
Ceftriaxone 350 45.1 49.5-60.2
Ciprofloxacin 72 65.3 24.1-46.9
Aztreonam 46 45.7 39.1-68.8
Levofloxacin 4 75 1.3-78.1 Meropenem 449 90.9 6.7-12.2
Trimethoprim/Sulfamet 67 94 1.9-15.4
Amikacin 448 85.3 11.6-18.4
Clindamycin 71 84.5 8.4-26.5 Gentamicin 445 62.5 33.0-42.2
Erythromycin 71 78.9 12.7-32.7 Tobramycin 448 60.7 34.8-44.0
Nitrofurantoin 7 85.7 0.8-58.0 Ciprofloxacin 244 57.4 36.4-49.1
Linezolid 85 100 0.0-5.4 Levofloxacin 453 68.7 27.1-35.8
Vancomycin 21 61.9 19.0-61.3 Trimethoprim/Sulfamethox 367 52 42.8-53.2
Fosfomycin 26 65.4 17.9-55.6
Chloramphenicol 52 76.9 13.0-37.2
Nitrofurantoin 21 61.9 19.0-61.3
Tetracycline 79 48.1 40.4-63.2 Tetracycline 49 40.8 44.3-72.7

Courtesy of Dr Hesty Lusinta, SpMK

Rekomendasi untuk
Memperpanjang Usia Kebergunaan
Antibiotik
• Penggunaan antibiotik secara optimal
• Mengontrol / melarang
penggunaan antibiotik atau golongan
antibiotik secara selektif
• Penggunaan antibiotik secara bergiliran
dengan pola tertentu
• Penggunaan kombinasi antibiotik untuk
mencegah resistensi
Schlaes, D.M. et al. Clin. Infect. Dis.,1997
Walsh, Nature, 2000
 • An antibiogram is an overall profile of
antimicrobial susceptibility testing results of
a specific microorganism to a battery of
antimicrobial drugs
What is an
Antibiogram?
 Antibiogram Uses
• Help guide the clinician and pharmacist in
selecting the best empiric antimicrobial
treatment in the event of pending microbiology
culture and susceptibility results.

• Useful tools for detecting and monitoring

trends in antimicrobial resistance.

• Help the antibiotic formulary and

procurement.

(CLSI M39-A4)
• Analyse and present a cumulative
antibiogram report at least annually
• Include only final, verified test results.
• Include only species with testing data for ≥ Recommendations
30 isolates for Antibiogram
• Include only diagnostic (not surveillance) Report (1)
isolates

(CLSI M39-A4)
• Eliminate duplicate by reporting only the
first isolate of a species/patients/periods
irrespective body sites and AST profile
• Include only antimicrobial agents routinely Recommendations
tested.
for Antibiogram
• Do not reported supplemented agents
Report (2)
• Report %S and not include %I

(CLSI M39-A4)
• Streptococcus pneumoniae and
cefotaxime/ceftriaxone/penicillin: %S use
meningitis and non-mengitis break point. For
Penicillin: Consider %S using oral break point
Recommendations
• Stretococcus Viridans and peniciliin : List
both %S and %I for Antibiogram
• S. aureus: list the %S for all isolates and the Report (3)
MRSA subsets
(CLSI M39-A4)
Factor May Affect Cumulative
Antibiogram Data

• Patient population
• Culturing practice
• Laboratory antimicrobial
susceptibility testing and
reporting policy
• Temporal outbreaks
Antibiogram Limitations
• It should not be relied upon as the sole tool
for guiding therapy
• Minimum inhibitory concentrations (MICs) are
not included → “MIC creep” will not be
detected
• Data do not take into account patient factors:
• History of antimicrobial use
• Ages
• Underlying medical condition
Antibiogram
Limitations
• Data are the result of single organism-
antimicrobial combinations, therefore
do not show trends in cross-resistance
of an organism to other drugs, nor do
they reveal synergistic properties of
antimicrobials used in combination
• Data may not be generalizable to
specific patient populations or locations
of a healthcare facility if the antibiogram
is compiled using hospital- or healthcare
system-wide data
PPRA : Program
Pengendalian
Resistensi
Antimikroba di
Rumah Sakit
PMK no.8/2015: Pasal 6
1. Setiap rumah sakit HARUS melaksanakan Program Pengendalian
Resistensi Antimikroba secara optimal.
2. Pelaksanaan Program Pengendalian Resistensi Antimikroba
sebagaimana dimaksud pada ayat (1) dilakukan melalui:
a. Pembentukan tim pelaksana Program Pengendalian Resistensi
Antimikroba;
b. Penyusunan kebijakan dan panduan penggunaan antibiotik;
c. Melaksanakan penggunaan antibiotik secara bijak
d. Melaksanakan prinsip pencegahan pengendalian infeksi
Pembentukan
Tim PPRA

• Klinisi perwakilan
SMF/bagian
• Keperawatan
• Instalasi farmasi
• Laboratorium mikrobiologi
klinik
• Komite/tim pencegahan
pengendalian infeksi (PPI)
• Komite/tim farmasi dan
terapi (KFT).
Tugas Pokok Tim PPRA
• Membantu Kepala/Direktur rumah sakit dalam:
• menyusun kebijakan tentang pengendalian resistensi antimikroba;
• menyusun kebijakan dan panduan penggunaan antibiotik rumah sakit;
• melaksanakan program pengendalian resistensi antimikroba di rumah
sakit;
• mengawasi dan mengevaluasi pelaksanaan pengendalian resistensi
antimikoba di rumah sakit;
• Menyelenggarakan forum kajian kasus pengelolaan penyakit infeksi
terintegrasi;
• Melakukan surveilans pola penggunaan antibiotik;
• Melakukan surveilans pola mikroba penyebab infeksi dan kepekaannya
terhadap antibiotik;
• Menyebarluaskan serta meningkatkan pemahaman dan kesadaran tentang
prinsip pengendalian resistensi antimikroba, penggunaan antibiotik secara
bijak, dan ketaatan terhadap pencegahan pengendalian infeksi melalui
kegiatan pendidikan dan pelatihan;
• Mengembangkan penelitian di bidang pengendalian resistensi antimikroba;
• Melaporkan pelaksanaan program pengendalian resistensi antimikroba
kepada Kepala/Direktur rumah sakit.
Tugas Lab/dokter Mikrobiologi Klinik
Melakukan pelayanan pemeriksaan
mikrobiologi

Memberi konsultasi dan terlibat dalam tata

laksana pasien infeksi melalui visite ke
bangsal pasien bersama tim

Memberi informasi pola mikroba dan pola

kepekaan/resistensi secara berkala setiap
tahun
Tugas SMF/Bagian
Menerapkan prinsip penggunaan antibiotik secara
bijak dan menerapkan kewaspadaan standar.

Melakukan koordinasi program pengendalian

resistensi antimikroba di SMF/bagian

Melakukan koordinasi dalam penyusunan panduan

penggunaan antibiotik di SMF/bagian.

Melakukan evaluasi penggunaan antibiotik

bersama tim.
Tugas Instalasi Farmasi
Mengelola serta menjamin mutu dan ketersediaan antibiotik
yang tercantum dalam formularium.

Memberikan rekomendasi dan konsultasi serta terlibat dalam tata

laksana pasien infeksi, melalui: pengkajian peresepan, pengendalian dan
monitoring penggunaan antibiotik, visite ke bangsal pasien bersama tim.

Memberikan informasi dan edukasi tentang penggunaan

antibiotik yang tepat dan benar

Melakukan evaluasi penggunaan antibiotik bersama tim

Tugas Bidang Keperawatan
Menerapkan kewaspadaan standar dalam
upaya mencegah penyebaran mikroba
resisten.

Terlibat dalam cara pemberian antibiotik

yang benar

Terlibat dalam pengambilan spesimen

mikrobiologi secara teknik aseptik.
Tugas Komite/tim farmasi dan terapi (KFT)
Berperanan dalam menyusun kebijakan dan
panduan penggunaan antibiotik di rumah
sakit

Memantau kepatuhan penggunaan antibiotik

terhadap kebijakan dan panduan di rumah
sakit

Melakukan evaluasi penggunaan antibiotik

bersama tim
Tugas Komite/tim pencegahan pengendalian
infeksi (KPPI)
Penerapan kewaspadaan standar

Surveilans kasus infeksi yang disebabkan

mikroba multiresisten

Cohorting/isolasi bagi pasien infeksi yang disebabkan

mikroba multiresisten

Menyusun pedoman penanganan kejadian luar biasa mikroba

multiresisten
Indikator Mutu PPRA
• Perbaikan kuantitas penggunaan antibiotik
• Perbaikan kualitas penggunaan antibiotik
• Perbaikan pola kepekaan antibiotik dan penurunan
pola resistensi antimikroba
• Penurunan angka kejadian infeksi di rumah sakit
yang disebabkan oleh mikroba multiresisten
• Peningkatan mutu penanganan kasus infeksi secara
multidisiplin, melalui forum kajian kasus infeksi
terintegrasi.
Empiric therapy vs directed therapy

Empiric therapy approach (85%) Directed therapy approach (15%)

• Infection not well defined • Infection well defined
(“best guess”) • Narrow spectrum
• Broad spectrum • One, seldom two drugs
• Multiple drugs • Evidence usually stronger
• Evidence weeker • Less adverse reactions
• More adverse reactions • Less expensive
• More expensive
Empiric Antibiotic Therapy
Empiric prescribing guidelines are appropriate for most patients, but they do not replace clinical judgment.

Clinicians should always consider patient-specific information (e.g., prior culture results, recent antimicrobial therapy
and immune status) when selecting therapy

They should also reassess their initial treatment choice (continue, modify, de-escalate, discontinue) once cultures are
available.

An efficient way to develop local empiric antibiotic regimens is to use established national or provincial guidelines,
and/or guidelines from other institutions.

It is important to ensure other guidelines are adapted for the institution.

Local guidelines should also be updated regularly as new information becomes available.
Choice of Empiric Antibiotic
Therapy is Based on:
• The site of infection.
• Common pathogens encountered.
• Local epidemiology and resistance
patterns.
• Evidence and clinician consensus.
• Antimicrobial stewardship principles.
• Formulary availability.
• Antimicrobial costs.
De-escalation of Antibiotic Prescription

Diagnosis of bacterial
infection Microbiological
Examination
Empiric Antibiotic
treatment Microbiological
Examination
Result:
Definitive Antibiotic Identification
treatment and AST
Definitive Antibiotic Treatment

Microbiological
culture and AST

Pathogenic
Colonization
/Infection

No Antibiotic Sensitives Resistant/MDRO

Treatment

Prescript recommended Optimization Antibiotics

Antibiotics PK/PD Combination
Summary
• Antimicrobial Resistant is a global
threat
• Antibiogram is a powerful tool to
develop guideline of antibiotic
empiric therapy
• Antimicrobial stewardship in
hospitals as a massive
multidiscipline approach should
be implemented in every hospital