Curriculum Vitae

Prof Dr dr Sri Rezeki S Hadinegoro Sp.A(K)

Staf pengajar
Departemen Ilmu Kes Anak FKUI/RSCM
Jakarta
• Pendidikan
– Dokter umum – FK.UNPAD 1972
– Spesialis anak – FK.UI 1983
– Doktor – FK.UI 1996
– Guru Besar – FK.UI 2000

• Organisasi
– Ketua Indonesian Technical Advisory Group on Immunization (ITAGI)
– Anggota Satuan Tugas Imunisasi IDAI
– Anggota KOMNAS PP KIPI – KEMKES
– Board member of Asian Society of Pediatric Infectious Disease (ASPID)
– Member of Asia-Pacific Dengue Prevention Board (APDPB)
– Member of Asia Dengue Vaccine Advocacy (ADVA)
– President Elect of International Society of Tropical Pediatrics (ISTP)
 General Principles of
Prudent Used of Antibiotics

Sri Rezeki Hadinegoro

Department of Child Health
Medical Faculty, University of Indonesia
Dr Cipto Mangunkusumo hospital Jakarta

Presented at PKB – IDAI Jawa Tengah, Semarang 8-9 January 2017

 Outlines
• Host-agent-drugs interaction
• Selecting an antibiotics
• Antibiotic stewardship
• Appropriate antibiotic usage (de-
escalating, switching, OPAT)
• Antibiotic failure
• Antibiotic resistance
• Summary
 The aims

• To strengthen global defenses against

infectious disease by ensuring access to
effective treatment and promoting
appropriate antibiotic use to contain
drug resistance
The Alliance for the Prudent Use of Antibiotics (APUA)
Facts about antibiotic use

The Alliance for the Prudent Use of Antibiotics (APUA)

The component of therapy in
Infectious Diseases
 Infant, elderly,
immunocompromized

Physician as the 1st author

need information & education

The role of
pharmacy Bacteria
identification
 General principles of the
treatment of infection
• Antimicrobial agents are among the most
commonly prescribed drugs.
• The major impact on control of most bacterial
infections
• Concerns that unnecessary use is compromising
their beneficial effect
• The choice of drug,
– Its dose, route, frequency of administration.
– Depend on the pharmacological & pharmacokinetic of
particular agent and adverse reactions of the drugs
Gallagher JC, Mac Douglall C. Antibiotics simplified, 2009
The benefit of
antibiotic
Cure for
bacterial
infection only! Correct
dose &
Bacterial duration
elimination &
Suppress eradication
the number
of
pathogen
Kill bacterial
pathogen
caused
disease
 Important questions to answer
routinely before selecting an antibiotic
(1)
• Is an antibiotic indicated?
• Have appropriate specimen been obtained,
examined, and cultured?
• What organisms are most likely?
• If several antibiotics are available, which is
best?
– Drug of choice, pharmacokinetics, toxicology, cost,
narrowness of spectrum, bactericidal compared
with bacteriostatic agents.
Gallagher JC, Mac Douglall C. Antibiotics simplified, 2009
 Important questions to answer
routinely before selecting an antibiotic
(2)
• Is an antibiotic combination appropriate?
• What are the important host factors?
• What is the best route of administration?
• What is the appropriate dose?
• Will initial therapy require modification after
culture data are returned?
• What is the optimal duration of treatment, and
is development of resistances during
prolonged therapy likely to occur?
Gallagher JC, Mac Douglall C. Antibiotics simplified, 2009
 Selecting the antibiotic
Any indication Dose,
Empirical or
for antibiotic frequency,
definitive
use? route, duration

What is the
Mono-therapy Tailoring or
microorganis
/combination? switching
m?

How to
choose the PK/PD? Side effect?
antibiotic?
How antibiotic kill bacteria?
 Clinical assessment
• Clinical evaluation should define the anatomical
location and severity of the infective process.
• Although such diseases may be caused by wide
variety of organisms, the range of pathogens are
usually limited.
• The pattern of susceptibility reasonably
predictable.
• Permits a rational selection of chemotherapy in
the initial management of such infections
Gallagher JC, Mac Douglall C. Antibiotics simplified, 2009
 Attention in
Antimicrobial
Use
Misdiagnosis
Emergence and re- Unavailable medical
emergence of infectious facilities
diseases
Improper diagnostic
Contributed to emergence of facilities
drug resistance
and laboratories

Not indicated,
Increased likelihood Inappropriate antibiotics
use,
of prescribing wrong
Antibiotics of poor quality
medication and potency,
Inappropriately low doses
Strategies of Antibiotic Use
• Cure the infection completely
• Avoid pathogen transmission in the ward
• Established the clinical diagnosis and look
for proven cause
• Effective therapy and prudent use
• Follow the antibiotic usage guidance
• Training of antibiotic use (certified)
• Build the Hospital Committee of Antibiotic
Use (physician, pharmacy, board of
hospital managers)
 Antibiotic Stewardship
• Explain the antibiotic resistance
• Increased hospital cost
Education • Follow the guidance
• Academic detailing to all
prescriber

• Restriction in class & number of

antibiotics
Restriction • Restriction in antibiotic use
• Follow the antibiotic use
guidance
• Antibiotic recycling
 Benefits and Challenges
• Increase patient’s survival rate
• Decrease hospital cost
Benefits • Increase the level of community
health

• Limited of diagnostic laboratory

facilities
Challenges • Close team work (clinician,
clinical microbiologist, clinical
pharmacy)
• Improvement of hospital policy
Empirical therapy
Empirical
based on clinical Definitive therapy
diagnostic and
suspected
& Based on positive
microorganism Definitive result of culture &
sensitivity test
Drug of choice and
alternative drugs Therapy

Clinical indication : treatment of the

disease and etiology organisms
Site of infection (penetration of drugs)
Dosages of antibiotic
Renal impairment
Administration
 Empirical antibiotic Therapy
(proportional therapy)
• Use of broad spectrum antibiotic which do not
know yet the bacteria as a cause of infection

• Pro & contra

– Pro: to decrease the risk of complication or severity
of the disease
– Contra: patient do not suffer from bacterial infection
or no proven cause

El-Radhi. 2009. Clinical manual of fever in children

Burke A, Cunha. Antibiotic Essentials, 2010
 Indication of Empirical Therapy
Clinical & laboratory results supported infection, but
no proven cause by microbiology examination

Selection
Depend on Extended Clinical
epidemiology empirical judgement
Susceptibility therapy No bacterial
test
Prolonged culture
No more than 72 empirical therapy
hours Negative
after 72 hours bacterial culture
but clinal support
to infection
 Laboratory Assessment
• Few infective condition present a typical
picture with a definitive clinical &
microbiological diagnosis without laboratory
examination
• Whenever possible a clinical diagnosis
should be supported by laboratory
confirmation.
• Strong clinical suspected, therapy should be
given as soon as possible; while lab
assessment should be taken
• Burke
Serological test is important to antigen
A, Cunha. Antibiotic Essentials, 2010
detection
Bacterial identification is needed
Suspected
bacterial
infection

Definitive therapy Empirical therapy by

Narrow spectrum of guessing the cause of
antibiotic and match to pathogen & susceptible
susceptibility test to antibiotic

Pathogen Lab examination

identification & Blood culture, urine,
susceptibility test lCS, sputum
 Definitive therapy
Example
• Clinical Indication: typhoid fever cause by
Salmonella typhi
• Site of infection: small bowel, bile; penetration of
drugs is good
• Dose: chloramphenicol 100 mg/kg/day q 6 h (IV
push over 3-5 min or IV infusion over 15-30 min), for
10 days
• Renal impairment: creatinine clearance 10-30
ml/min: administer every 6 -12 hrs; Clcr <10 ml/min:
every 12 hrs
• Preparations: injection 125 mg, 500 mg and 1 g per
vial
• Administration: IM or IV
Gatchalian B. Handbook of PID. 2007
24
Supporting therapy
• Adequate rehydration
• Improve oxygenation
• Correction of acid-base imbalance
• Correction of electrolytes
disturbances
• Keep in good nutrition state
 Appropriate Antibiotic Use
• De-escalation therapy
• Switching antibiotic
• Outpatient Parenteral Antibiotic Therapy
(OPAT)
 Key point of
Streamlining/De-escalation Therapy
Decrease antimicrobial exposure by replacing
excessively broad empirical antimicrobial therapy with
more targeted therapy once culture results become
available

• Empirical therapy may allow for more targeted

therapy1
• Discontinuation of empirical antibiotic therapy if culture
results and clinical signs indicate absence or
eradication
Kollef of infection1
MH. Drugs. 2003;63:2157-2168.
 Streamlining/De-escalation
Therapy
• Advantages
– Decreases antimicrobial exposure
– Reduces risk of antibiotic resistance
– Contains cost
– Potential decrease in toxicity and super-infection
• Disadvantages
– Time delay for culture results
– Perceived difficulty in switching from broad-
spectrum antibiotics to narrow-spectrum
antibiotics
Kollef MH. Drugs. 2003;63:2157-2168.
Streamlining/De-escalation Therapy
Serious Infection Suspected

Begin empirical antibiotic (Abx) treatment with a

combination of agents targeting the most common
pathogens based on local data

Yes No
Pathogen identified?

Deescalate antimicrobial based on results Continue initial treatment

of clinical microbiology data

Reassess after appropriate time frame

Significant clinical improvement after Yes
48-96 hours of antibacterial treatment?
No
Search for superinfection, abscess Discontinue Abx after 7-14 days based on
formation, noninfectious cause of site of infection and clinical response
symptoms, inadequate tissue penetration
of Abx
Kollef MH. Drugs. 2003;63:2157-2168.
 Clinically
unstable
Switching therapy
A
Point of clinical stability

B Early Switch
Clinical Iv to oral
Severity of disease

Improvemen
Intravena t
antibiotic
Clearly Clinical Improvement
C

Oral
Out patient
administration

Time of illness
Ramirez JA., 2002
Evaluation of
antibiotic use
by Gyssen
 Quality of Antibiotic Use
assessment by Gyssens Criteria
Category
I No indication for giving the antibiotic
II Correct indication but incorrect dose, interval and
route of antibiotic use
III Correct indication with correct dose, interval, route but
not incorrect in duration of antibiotic use
IV Correct indication with correct dose, interval, route but
and duration of antibiotic use, but incorrect of
selecting the antibiotic
Outpatient Parenteral Antibiotic
Therapy (OPAT)
• Assessment before starting therapy
– patient’s general medical condition,
– the infectious process,
– the home situation is necessary
• These responsibilities
– include establishing a diagnosis,
– prescribing treatment,
– determining the appropriate site of
care,
– monitoring during therapy,
– assuring the overall quality of care
 Outpatient Parenteral Antibiotic
Therapy (OPAT)

• Antimicrobial selection for OPAT is

– different from that for therapy in the hospital.
– once-daily drug administration has many advantages.

• Regular clinical and laboratory monitoring of

patients receiving OPAT is essential and varies
with the antimicrobial chosen
Infections treated with OPAT
Antimicobial ranked used for OPAT
 Antibiotic Failure
• Microbiologic factors
– In vitro susceptibility but
ineffective in vivo
– Antibiotic tolerance with gram-
positive cocci
– Treating colonization (not
infection)
• Antibiotic factors
– Inadequate of:
coverage/spectrum, antibiotic
blood levels, antibiotic tissue
levels, antibiotic activity in
tissue
– Drug-drug interaction:
antibiotic inactivation,
antibiotic antagonism
Burke A, Cunha. Antibiotic Essentials, 2010
• Antibiotic penetration
problems
– Undrained abscess
– Foreign body-related infection
– Protected focus (e.g. cerebrospinal
fluid)
– Organ hypoperfusion /diminished
blood supply: chronic osteomyelitis,
chronic pyelonephritis
• Non infectious diseases
– Medical disorders mimicking (e.g.
SLE)
– Drug fever
• Antibiotic unresponsive
infectious diseases
– Viral infections
– Fungal infections
 Evaluation of Therapy
• Compliance
• Complications
Empirical • Other focal

Temp o C
therapy  infections
• Ab resistance
• Wrong D/
Failed

37.50 C

Evaluation
 Clinical
 Lab/CXR Cured
 LP, etc

1 2 3 4 5 6 7 8 9 10
Day of illness
 Antibiotic Failure
Suhu 0C
Antibiotic th/ Adjusted therapy

Fever persist

?
37,5

WBC Complications
Conciousness Transaminase Other focal inf
Complications CXR Ab resistance
Other signs/symptoms LP, CT-scan, etc Suboptimal dose
Wrong D/
Drug fever

0 1 2 3 4 5 6 7 8
Hari rawat
 Inappropriate use of
antibiotics
Increase in
antibiotic use Increase in
resistant strains
Limited treatment
alternatives
• more antibiotics
• increased Ineffective empiric
mortality therapy
• increased morbidity
• more antibiotics
Increased
use of Increased
healthcare hospitalization
resources • more antibiotics
The Alliance for the Prudent Use of Antibiotics (APUA)
 The CDC 4 Strategies Campaign to Prevent
Antimicrobial Resistance in Healthcare settings
Prevent infection
Preventing infections and complications
will decrease antimicrobial use

Dx and Treat Infection

Appropriate antimicrobial therapy save
lives

Use Antimicrobials Wisely

:Programs to improve antimicrobial use are
effective.

Prevent transmission
Health care personnel can prevent the
spread infections from patient to patient.
Campaign to Prevent Antimicrobial Resistance in Healthcare Settings:
42
http://www.cdc.gov/drugresistance/healthcare/identitypiece.htm
12 Steps to Prevent Antimicrobial
Resistance Among Hospitalized
Children

1. Prevent Infection
– Step 1. Vaccinate hospitalized children and
staff
– Step 2. Get the devices out

2. Diagnose and Treat Infection Effectively

– Step 3. Use appropriate methods for
diagnosis
– Step 4. Target the pathogen
– Step 5. Access the experts
43
 12 Steps to Prevent Antimicrobial
Resistance Among Hospitalized
Children
3. Use Antimicrobials Wisely
– Step 6. Practice antimicrobial control
– Step 7. Use local data
– Step 8. Treat infection, not contamination or colonization
– Step 9. Know when to say “no”
– Step 10. Stop treatment

4. Prevent transmission
– Step 11. Practice infection control
– Step 12. Practice hand hygiene

44
 Multi disciplinary Approach
• Collected data based and identifies the problems
• The strategy of antibiotic use
• Drug formularium
• Antibiotic use guidelines
• Restricted the use of antibiotic, prior approval for
certain antibiotic
• Use and follow the clinical pathways
• Post prescribing evaluation
• Switching-intravenous to oral conversion
• Prescriber education- academic detailing

Paskovaty, Pflomm,Myke, Seo,2005

 Summary
• Antibiotic use should depend on indication
either clinical or lab result
• Guideline of indication and selecting
antibiotic is mandatory
• Antibiotic use in each patient should be
evaluated
• Supporting therapy needed to get a maximal
result
• Prudent antibiotic use will give better patient
care beside prevented the antibiotic
resistance