WISELY USE OF ANTIBIOTIC

TARALAN TAMBUNAN
ARCP – RSCM, JAKARTA

Objective:
1. Understanding of AM global resistance problem
2. National strategy to combat the emergence and
spread AM resistance
- Prevent selection : Wisely use of AM
- Prevent transmission : General precaution
standard
3. The importance of Antimicrobial Stewardship
Program (ASP)
 The problem of AM/AB resistance
 AM/AB resistance: global thread & challenge
- S. penumonia
- Ps. aeruginosa
- MRSA, VRE, MDR Gram-negative bacilli
- Acinetobacter banmannii
Yeoh, SF. ACCP, Singapore 2010.

 Widespread use of AM/AB: correlated with increased incidence

of bacterial resistance
Follath et al. Eur J Clin Microbiol, 1987.

 Appropriate changes in AB use can lead to recovery of susceptibility

Ballow et al. Microbiol Infect Dis, 1992.
Reducing the use of antibiotics in animal husbandry
 MRSA DAN PAN-RESISTEN

Jan –Juni 2011 Juli – Des 2011 Jan-Juni 2012 Juli-Des 2012
jumlah % R Jumlah %R Jumlah % Jumlah %R
R
MRSA 26/ 136 19 36/163 22 242 19 35/192 18

Pan 7 12 60 178
resisten

Ref. Tonny Loho, RSCM 2014

Discovery of new classes of antibacterial drugs
(1930’s to 2000’s)
 Kecepatan
penemuan
antibiotik

Timbulnya
resistensi
kuman

- Post antibiotic era

- Kembali ke zaman
pra antibiotik
- Peningkatan kematian
karena penyakit infeksi
Bagan
Spekulatif
Waktu
7
 Kecepatan
GOAL PPRA
penemuan
antibiotik

Timbulnya
resistensi
kuman

prevalensi
AMR
Surveillance
• standar
• berkelanjutan
Bagan
Spekulatif Waktu
8
 Emergence of antimicrobial resistance

- Increase use - AM resistance

- Over use - Collateral damage
Inappropriate
- Misuse use
- Increase morbidity/
- Under use mortality
- Higher cost

Need AM policy to control

AM usage!

Ref. WHO policy perspective on medicines:

containing antimicrobial resistance.
WHO, Geneva, 2005
Prevent AM/AB resistance in health care settings

Prevent Wisely use

selection of AM/AB

Prevent General
transmission precaution
standard

* WHO report in infectious disease. WHO/CDS/2000.2

* CDC campaign to prevent AM resistance in health care
settings.
http://www.cdc.gov/drugresistance/healthcare/
ha/12steps_HA.htm
 GLOBAL ACTION PLAN
1. Improving awareness & understanding of antimicrobial resistance
through effective communication, education & training

2. Strengthening the knowledge & evidence base through surveillance &

research

3. Reducing the incidence of infection through effective sanitation, hygiene

and infection prevention measures

4. Optimizing the use or antimicrobial medicines in human & animal health

5. Developing the economic case for sustainable investment that takes

account of the needs of all countries & to increase investment in
new medicines, diagnostic tools, vaccines & other interventions

6. Strengthening International collaboration multidisciplinary to promote

research & implementation of antimicrobial resistance containment
 NATIONAL ACTION PLAN ON TACKLING
OF ANTIMICROBIAL IN INDONESIA (2017-2022)
(draft in human health)

1. Improving awareness & understanding of antimicrobial resistance

through effective communication, education & training

2. Strengthening the knowledge & evidence base through surveillance &

research

3. Reducing the incidence of infection through effective sanitation, hygiene

and infection prevention measures

4. Optimizing the use or antimicrobial medicines in human & animal health

5. Prepare the economic case for sustainable investment, international

collaboration & increase investment in new medicines, diagnostic
tools, vaccines & other interventions.
 National strategy to combat the emergence
and spread AM resistance

National-wide surveillance system

Pedoman umum penggunaan antibiotik

(Kemenkes RI 2011)

Hospital guidelines of AB use + SOP

(ARCP (PPRA))

Dept./Unit/Inst.
Guidelines of AB use
- Internal medicine
- Surgery
- Obs.-gyn
- Child health
- Etc.
2016
 ALUR SISTEM PENGENDALIAN
RESISTENSI ANTIMIKROBA

Panitia Farmasi dan Tim Mikrobiologi

Terapi Klinik

an
m
Ku
Ke tibi

ta
Pe
an
bi oti
jak k
an

PPRA Laporan
Tim PPRA + DIREKSI
s Da
i len Pokja PPRA ta
An
e
S urv ti bio
ta t ika
Da

Sub Komite PPIRS Tim Farmasi Klinik

 STRUKTUR ORGANISASI
DIREKTUR RS

Tim PPRA Pilar PPRA

Ketua 1. Klinisi/wakil SMF
Wakil Ketua 2. Keperawatan
Sekretaris 3. Instalasi farmasi
Anggota 4. Lab. Mikrobiologi klinik
5. Komite PPI
SMF/Bagian 6. KFT
 TUGAS TIM PPRA
 Membantu pimpinan dalam:
- Menerapkan kebijakan-kebijakan tentang pengendalian resistensi
antimikroba (integrasi dengan 4 Pilar)
- Menetapkan kebijakan pengendalian penggunaan antibiotik
- Menetapkan program pengendalian resistensi antimikroba (PPRA)
- Memonitor dan mengevaluasi PPRA
- Menyelenggarakan forum diskusi/kajian pengelolaan penderita
penyakit infeksi
- Menyebarluaskan dan meningkatkan pemahaman dan kesadaran
tentang prinsip-prinsip pengendalian resistensi antimikroba yang
terkait dengan penggunaan antibiotik secara bijak
- Mengembangkan penelitian yang terkait dengan PPRA

Ref. PPRA RSCM: SK Dirut RSCM no. 7139/TU.K/34/VII/2009

 KOMITE FARMASI DAN
TERAPI
 Pengendalian
pedoman
penggunaan antibiotik
 Kebijakan penggunaan antibiotik
(antibiotic policy)
 Pembuatan & revisi pedoman
penggunaan antibiotik (antibiotic
guideline)
 Surveillancepenggunaan
antibiotik Drug Use Study

Ref. Kuntaman & Paraton H. Workshop Pengampu PPRA, Denpasar 2011

 KOMITE PPI
 Pengendalian penyebaran mikroba
resisten
 Standar Precaution (kewaspadan standar)
 Isolasi penderita
 Penanganan unit kerja sumber mikroba
resisten (source control)
 Surveillance mikroba resisten
 Menyusun pedoman-pedoman terkait

Ref. Kuntaman & Paraton H. Workshop Pengampu PPRA, Denpasar 2011

 PELAYANAN MIKROBIOLOGI KLINIK
 Laboratorium Mikrobiologi
 Identifikasi dan uji sensitivitas
 Hasil pemeriksaan mikrobiologi

 Konsultasi / Visitasi / Patient care

 Bersama klinisi ikut terlibat merawat
pasien infeksi.
 Turn Around Time report

 Informasi Pola kuman

 Pengelolaan data mikroba
 menerbitkan informasi peta medan
secara berkala
Ref. Kuntaman & Paraton H. Workshop Pengampu PPRA, Denpasar 2011
 PELAYANAN FARMASI KLINIK
 Pengelolaan dan Penggunaan antibiotik
 Menjamin ketersediaan dan mutu antibiotik

 Konsultasi / Visitasi / Patient care

 Bersama Tim terlibat merawat pasien
infeksi ward pharmacist
 Mengkaji peresepan antibiotik
 Mengendalikan pemberian antibiotik
 Memonitor penggunaan antibiotik

 Informasi/konseling obat antibiotik

Ref. Kuntaman & Paraton H. Workshop Pengampu PPRA, Denpasar 2011

 THE CONCEPT OF
INFECTIOUS DISEASE INTEGRATED SERVICE TEAM

KLINISI PERAWAT/BIDAN

SKFT
DALIN

FARMASI MIKROBIOLOGI
Klinik Klinik

Ref. Kuntaman & Paraton H. Workshop Pengampu PPRA, Denpasar 2011

 Hospital Guidelines Antibiotic Use
1. Wisely use of AB
2. Surgical & non surgical prophylactic AB
3. Empirical treatment of AB
4. Definitive treatment of AB
5. Combination therapy
6. Antibiotic categories
7. Pharmaceutical aspect
8. Monitoring of effectivenes of AB
Ref. PPRA-RSCM, 2009
 OVERVIEW OF ANTIMICROBIAL THERAPY

● Antimicrobial therapy: to prevent/control infection

● Prescribing errors are common

- treatment of colonization
- suboptimal empiric therapy
- inappropriate combination therapy
- dosing and duration errors
- mismanagement of AB failure

● Inadequate consideration of
- AB resist,
- tissue penetration LIMIT THE EFFECTIVENESESS
- drug interaction OF AB THERAPY
- side effect

Ref. Cunha BA. Antibiotic essentials, 2012.

GENERAL PRINCIPLES OF
ANTIMICROBIAL THERAPY
1. Selecting and initiating antibiotic
regimen
2. Consideration for continuing AB
therapy
3. Special situations in infections disease
therapy
4. Judicious use of antimicrobial agents
Leekha S, Terrel CL, Edson RS:Mayo Clin Proc 2011;86:156-157
EMPIRIC VS DEFIVITIVE AB
THERAPY

 Initial empiric therapy

- guided by clinical presentation
- the most likely organism

 Definitive Therapy :
- use the narrow spectrum AB
SELECTING AND INITIATING AN AB REGIMEN
Accurate diagnosis
- defining the host : immunocompr, diabetes, age
- the site of infection
- clinical presentation  the most likely microbiological
etiology
- diagnostic specimen
- microbiological diagnosis
- detailed exposure history
- non infections condition for DD/

Leekha S, Terrel CL, Edson RS

Mayo Clin Proc 2011;86:156-157
Varley A J et al. Brit J Dnesth 2009;9:184-188
 Prudent use of AB
- Adequate data for diagnosis of infection(s)
- Right indication: treat infection not colonization
- AB selection: . efficacy
. safety
. suitability
. cost
- Right . dose
. interval
. route of administration
. duration
. Time of initiation
- Anaphylactic reaction?
- Patient education
Ref. - Gyssens 2005
- de Vries et al. Guide to good prescribing. WHO 1994
 IDEAL ANTIBIOTICS
 Provides empiric coverage for all community and nosocomial
pathogens
 Capable of tissue penetration
 Resistant to inactivation by bacterial enzymes
 High affinity for site target
 Must not readily stimulate bacterial resistance
 Minimum side effect
 Proven clinical efficacy

Blumer J,ICAAC 40th,September 2001

 Fundamentals of Empiric Therapy

- Epidemologic data/local data of AB profile & sensitivity

- Clinical condition:
Serious inf. :. brood spectum AB
. timeliness
. appropriateness
. duration of therapy
Mild inf. : Oral/parenteral

Ref. - Lawrence KL et al. Am J Respir-Crit Care Med. 2009;179:434-8.

- Peterson LR. CRIDTRHOPHID-ARCP. Faculty of Medicine Univ. of Indon.
March 10, 2012
 STRATEGY FOR EMPIRICAL
TREATMENT
Patient

Outpatient Hospitalized

Stable condition Severe or high risk

Escalation Deescalation

Antibiotic selection based on susceptibility and resistance pattern

Immunity status, co morbidity and organ dysfunction

Antibiotic monotherapy or combination

Pohan HT, 2005
 Initial Appropriate Therapy
 Empiric broad-spectrum therapy initiated at the first
suspicion of serious infection (HAP, VAP, Sepsis)
 Selection of antibiotic to ensure adequate coverage of
all likely pathogens
 Factors to consider when defining appropriate therapy:
- microbiologic data
- monotherapy vs combination therapy
- dose and dosing frequency
- penetration
- timing
- toxicity
- risk of influencing resistance
- prior antibiotic use
Kollef MH, et al. Chest 1999;115:462-474
Kollef MH. Clin infect dis 2000;31(suppl 4):S131-S138.
 CLASSIFICATION OF
ANTIBIOTICS
Class A Class B Class C
Aminoglicoside Cephalosporine gen III Teicoplanin
Penicillin Fluoroquinolone Linezolide
Cephalosporin gen.I,II gen III-IV Cefepime
Chloramphenicol Cefpirome
Fucidic acid Carbapenem
Lincosamide Tygecycline
Macrolide Ceftazidime
Nitroimidazol Pip-Tazo
Fluoroquinolone gen.I.II Vancomycin
Tetracyline Aztreonam
TMP-SMX
Fosfomicin
Polypeptide
 FACTORS IN ANTIBIOTIC SELECTION
A. Spectrum: - the basic for empiric therapy
- concentration-dependent kinetics
- time-dependent kinetics

B. Tissue penetration: - lipid solubility

- molecular size and tissue
- adequacy of blood supply
- presence of inflammation

C. Antibiotic resistance: - natural/intrinsic or acquired

- relative or absolute

D. Safety profile: avoid AB with serious/frequent side effect

E. Cost

Ref. Cunka BA. Antibiotic essential, 2012

 FACTORS IN ANTIBIOTIC DOSING

- Usual antibiotic dose: assumes normal renal &

hepatic function

- Dosing strategies: based on formula derived estimate

creatinine clearance

- For pediatric use Schwartzs formula

- Drug dose in infants/children are generally based on weight

Ref. Cunka BA. Antibiotic essential, 2012

DOSING STRATEGIES IN HEPATIC/RENAL INSUFFICIENCY

Hepatic insufficiency
- problematic: no hepatic counterpart to the serum creatinine to asses
liver function
- Severe liver disease: - decrease dose of hepatically-limited AB by 50%
- use AB eliminated by renal route

Renal insufficiency
- Cr. clearance 40-60 ml/min: decreased dose of renally eliminated AB
by 50% with normal usual dosing interval
- Cr. clearance 10-40 ml/min: 50% normal dose with double dosing interval
- Use AB eliminated by hepatic route in usual dose

Ref. Cunka BA. Antibiotic essential, 2012

DURATION OF AB THERAPY
Anecdotal record and expert opinion
 Prolonged course :

- adverse reaction
- problems of adherence
- resistant organism
- high cost
 Optimal duration :
- uncompl UTI: 3 days
- CAP 5 days
- VAP 8 days (?)
DURATION OF AB THERAPY (CONTD.)

Endocarditis

Osteomyelitis 4 – 6 weeks
Intra
abd. abscess
Fungal infection : weeks – month

 Individualized : based on clinicals and radiologic

response
 Need an expert in infections disease

Leekha S, Terrel CL, Edson RS

Mayo Clin Proc 2011;86:156-157
ANTIBIOTIC PROPHYLAXIS

Three principles for Succesful AB prophylaxis

1. Patient should be at high risk of infection.

2. The likely infecting organism and their susceptibility

should be known.

3. AB prop. only be administered at time of risk.

Varley AJ, Sule J, Absalom A.R.

Brit J. Anesth 2009;9:184-188
FACTORS FOR USE OF AB PROPH:
High risk groups :
 very young or very old age
 poor nutrition

 obesity

 diabetes

 smoking/history of smoking

 existing infection

 recent surgery

 extended hospital stay before the procedure

 certain congenital heart condition

Singh R, Singla P, Chandhany U Antibiotic Prophilaxis :

https://www.healthline.com/health/prophylactic-antibiotic-premedication.
 ANTIMICROBIAL PROPHYLAXIS
Recommended for various surgical procedure to prevent SSI.
 Should be :

- bactericidal
- non toxic
- in expensive
- active against the typical phatogen that can cause SSI
 Administered IV : 30-60 min. before surgical incision.

 Short duration  decreased toxicity

Enzler MJ, Berbari E, Osmon DR Mayo Clin Proc. 2011;86:686-701

WOUNDS CLASSIFICATION AND
RISK OF ENQUIRING SSI
 1. clean wounds : SSI rate :<2 %
- no inflammation
- elective, not emergency
- primarily closed
- Proph AB is not recommended
exept: clean surgery involving
the placement of a prothesis or implant

Singh R, Singla P, Chandhary u.

International J Pharma Reasearch and Health Siciences 2014;22:203-2014
2. Clean contaminated wounds : SSI rate :3-11%
- operation procedure enters into a colonized
viscus/cavity

- minimal spillage

- Prophylaxis AB is recommended
3. Contaminated wounds : SSI > 10 %
- major breaks in sterile technique
- gross spillage from GI tract
- the presence of infected bile/urine
- prophylaxis converted to treatment regimen

4. Dirty wounds : SSI rate > 20 %

- active infection +
- Empirical AB treatment is recommended

Singh R, Singla P, Chandhary u.

International J Pharma Reasearch and Health Siciences 2014;22:203-2014
 DURATION OF PROPHYLACTIC AB
 Aimed ; to reduce the incedence of SSI
 Tendency toward the use of shorter course
- In most surgery:single pre operative
- Caradiac surgery : - controversial area
- 48 hrs ?
- 56 hrs  32 hrs:NS
- Tunneled HD cath insertion : not recommended
- Extruded TDC insertion: Single pre op
- PD cath replacement : Single pre op

1. Kappeller R, at al J. Antimicrobial chemotherapy 2012;67:521-522

2. Hamonda K, at al J. Cardiothorasic surg. 2015:10:25
3. Salman L, Asif H : Semin Dial. 209;22:297-299
DURATION OF PROPHYLACTIC AB
(CONTD.)
 Renal transplantation : - single preop.
 Vascular intervention : - routine no AB

- special consideration
single preop.
 Non vascular Fluoroscopy:single preop.

1. Orlando G et al Transplan Proc. 2010;42:1118-1119

2. Venkatesan AM et al J. Vasc Interv Radiol 2010;21:1611-1630
Antibiotic Stewardship Program (ASP)

Background
- Increasing prevalence of resistant bacteria
MDRO: MRSA, VRE, VRSA, ESBL, etc
- Increased antimicrobial expenditures
- Increased morbidity & mortality
- Decreased in market research and development
- Focus on national quality organization
. Institute of health improvement
. National patient safety goal

Ref. - Yeoh SF. AACP Singapore, 2010

- Di Pentima MC. Pediatrics 2011;128:1062-70
ASP Core Elements
 Leadership commitment
 Accountability: physician
 Drug expertise: single pharmacist
 Action: implementing recommended action
(ex. Systemic evaluation of on-going treatment)
 Tracking: monitoring AB prescribing
 Reporting: regular: AB use, AB resistant
 Education: resistance, good prescribing

Ref. Central for Disease Control and Prevention, CDC 24/7

www.cac.gov.getsneart/healthcare/implementation/core-element/html
7 Nov 2014
 ASP STRATEGIC PLANNING
A. Main strategies
STRATEGY METHOD PIC ADVANTAGE(S)
Prospective 1. Qualitative + 1. Med. doctors 1. Improving quality
auditing quantitative (specialist in 2. Reduce cost
auditing inf.)
2. AM resistancy 2. Clin. Pharm
monitoring 3. Clin. Microb.

Formulary - AM/AB monitoring - Doctors in Direct control of

restriction card charge AM/AB usage
On AM/AB - Licensed prescribers - Supervisors  Reduce misuse
use - AM/AB
committee
- Clin. Pharm.

Ref. - Pedoman umum penggunaan AB. Kemenkes RI, 2011

- Mc Dongall C, Polk RE. Clin Microb Rev. 2005;18:636-56
 EVALUATION CATEGORY OF
ANTIBIOTICS USAGE BY GYSSENS
I. Correct Usage
II. 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 No Indication
VI Medical record is insufficient to be evaluated
 SUMMARY

 AM/AB resistance: major problem across the world

 Widespread use of AM/AB  increased incidence

of AM resistance

 Appropriate changes in AM/AB use can lead

to recovery of susceptibility

 Two strategies to prevent AM/AB resistance

- prevent selection: wisely use of AB
- prevent transmission: general precaution
standard
ARCP: Coordinating with 4 pillars
. Drug & therapeutic committee
. Clin. Pharm. Team
. Clin. Microbiology team
. Inf. Control committee

Integated service team  to control AB usage

. Hospital guidelines AB use

. Standard operating procedure
. Antibiotic stewardship program
 preventing antimicrobial resistance