Rational antibiotic usage in

pediatrics
Irene Ratridewi

Division of Pediatric Infectious diseases and Tropical Medicine

Faculty of Medicine University of Brawijaya Malang
Outline
• Introduction  include resistance awareness
• Antibiotics classification, spectrum, and indication
• How to differentiate between bacterial and viral infection
• How to choose the proper antibiotics
• How to manage non responders
• Common pitfalls of antibiotics usage

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INTRODUCTION
• Antimicrobial agents  kills or inhibits the growth of
microorganism
• Antibacterial (antibiotics)
• Antifungi
• Antivirus
• Antiparasites
• Antibiotics  common terminology for antibacterial 
benefits or problem?

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Benefits (pearl) of antibiotic usage
• Control the bacterial infections
• Decrease morbidities and mortality in severe bacterial infections
• In animal welfare  healthy animal (cattle)  healthy food
• Agriculture  reduce bacterial infections in plants  increase the
crops and provide good food

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Why antibiotics usage
 problems?

Solution:
Proper use of antibiotics 
reduce resistance

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Antibiotics
invention

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 Kecepatan
penemuan
antibiotik
Timbulnya
resistensi
kuman

- Post antibiotic era

- Kembali ke zaman
pra antibiotik
- Peningkatan kematian
karena penyakit infeksi
Bagan
Spekulatif Waktu
12

Slides: courtesy by Hari Paraton: Antibiotics stewardship workshop Ministry of Health of Indonesia 7
 Kecepatan GOAL PPRA
penemuan
antibiotik
Timbulnya
resistensi
kuman

prevalensi
AMR

Bagan
Spekulatif Waktu
13

Slides: courtesy by Hari Paraton: Antibiotics stewardship workshop Ministry of Health of Indonesia 8
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 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 ( (% understanding of AMR, % antibiotic consumption,% in Health health, ministry of
( % number of Health Facility included) education Agriculture and
decreasing antibiotic OTC))
OUTPUT

(Medical Doctor, veterinary, 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
Collaboratio
Collaborat n between
Collaborati Collaborati
ion of institution
on among on of
Realization of AMR Information system base on ministry of that
Realization of AMR Information system base health medical
health facilities agriculture concern in
on community setting faculty / profession
and antibiotic
university collegium
veterinary use
Existing system of AMR control in Health facilities and community
HEALTH PROVIDER

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)

11
Hospital ARCP Pathway 2016
• standardization of
Hospital AMR Program
AMRCC of MoH training
• Training of the Trainer
• research: AMR, Antibiotic
use, sepsis, AMR related
infection cost
14 National and 20
Provincials Referral • National AB - AMR
Hospitals Surveillance

110 Regional Private and District Primary

Referral Hospitals Hospitals Health Care

12
Classification, spectrum, and mode of action of antibiotics

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Spectrum of antibiotics

15
Bliss J Chang. The ultimate medical school rotation guide. 2021 16
How to differentiate between bacterial and
viral infection

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 How to differentiate between bacterial
infection and viral/other infection

Bacterial Viral

- Fever  usually - Fever (mild or

gradually increase sudden high
- Clear focal grade fever)
infections (usually): Viral infection complicated by bacterial infection - Systemic
SBI and non SBI disease
- More toxic - Skin rash
appearance for SBI - Persistent fever - Leucopenia
- Leucocytosis/leuco - Usually occur in complicated with
penia with viral infection or in lymphocytosis
neutrophilia (exept immunocompromised patient
pertussis  - Associated with HAIs
lymphocytosis)
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- ANC good predictor
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 SERIOUS BACTERIAL INFECTIONS

Bacterial meningitis
Bakteriemia
Sepsis
Severe skin and soft tissue infection
Urinary tract infection
Pneumonia
Osteomyelitis, septic arthritis
Infected by MDRO
Bacterial enteritis
Etc.

Escalation with 1st line empirical therapy

Take microbiology sample

Escalation/de-escalation 22
How to choose the proper antibiotics?
Broad spectrum Normal flora spectrum

Empirical antibiotics antibiogram Prophylaxis antibiotics

- Reserved Broad spectrum
- Very narrow spectrum

First case Healthcare definitive antibiotics Pre-operative procedure  cefazolin

/community associated
acquired infections
Deescalation to
Mostly: Moderate – severe
1st beta lactam  infection:
Ampicillin combination with
Amoxicillin Gentamycin Not improved Re-asses the diagnosis Microbiology
Ampi-sulbact (when beta lactamase producing bacteria is specimens
suspected)
2nd line antibiotics:
Evaluate clinical appearance and complete blood count 3rd gen cephalosporin
Ceftriaxone, cefotaxime

Improved deescalation Combination with

gentamycin when necessary 23
Clues and cues how to choose proper antibiotics
• 1st line antibiotics for non CNS infections  beta lactams, may combine
with aminoglycosides:
• Ampicillin or ampicillin-sulbactam alone
• Ampicillin or ampicillin-sulbactam with gentamycin
• 1st line antibiotics for CNS infections  3rd gen cephalosporine:
• Ceftriaxone 80-100 mg/kgBW/day  once daily or divided into 2 doses
• Cefotaxime 100 mg/kgBW/day  divided into 3 doses
• SKIN TEST is NOT RECOMMENDED for any antibiotics
• Observe the symptoms, clinical appearance and complete blood count
within 3 days,
• better  continue antibiotics until 2 days of good clinical appearance and laboratory
exams (usually 7-10 days)
• No significant improvement or worse  reassess the diagnosis  still SBI 
escalation to 2nd line empirical therapy, wait for microbiology results

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• 2nd line antibiotics for empirical therapy:
• 3rd gen cephalosporine antibiotics (ceftriaxone, cefotaxime)
• Ceftazidime  limit as anti-pseudomonas
• Cefepime  definitive antibiotics (not 2nd line)
• Ceftaroline  very limited indication
• Cefixime  2nd line oral antibiotics  UTI, typhoid fever, pneumonia
• Criteria for empirical antibiotics  broad spectrum
• Deescalate as soon as possible to avoid the resistance of normal flora
to antibiotics
• Carbapenems  3rd line antibiotics as definitive therapy
• Evaluation for antibiotic usage: clinical appearance (number 1);
complete blood count (ANC, WBC count, sometimes platelet), CRP
(marker for inflammation), procalcitonin (more likely to bacterial
infection  bacteriemia)

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 PROCALCITONIN
• Procalcitonin synthesis in systemic inflammation that is caused by bacterial infection,
induced in nearly all tissues and released into the blood.
• Known triggers for synthesis include bacterial toxins, such as endotoxin and cytokines
including tumor necrosis factor (TNF)-α, IL-1ß, and IL-6
• Bacterial infections cause procalcitonin to rise, typical bacteria (Streptococcus
pneumoniae or Haemophilus influenzae), fungi (Pneumocystis jirovecii ), Candida and
parasites (malaria)
• Noninfectious causes of systemic inflammation, such as shock, trauma, surgery, burn injury,
and chronic kidney disease
• Serum procalcitonin levels rise within 2-4 hours in inflammatory stimulus, peaking within 24
to 48 hours, levels decline by about 50 percent every 1 to 1.5 days when the resolution of
inflammation

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 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
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PITFALLS ANTIBIOTICS USAGE
Route of administration 
ORAL or INTRAVENOUS
OVERUSE/MISUSE
Indication, frequency,
dose, and duration

Incorrect Drugs interaction

prescription
adverse effects
OFF LABEL antibiotics
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How to avoid pitfalls?
• Use local guidelines (local hospital antibiograms)
• Read the leaflets carefully (dose, drug interactions, route of
administration, reconstitution, effective time after reconstitution)
• For off label antibiotics  use while no other effective antibiotics due
to microbiology results  educate the parents (example: quinolones)

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Challenge due to antibiotics usage
• No significant changes towards new antibiotics invention
• Increase of MDROs
• Diagnostic tools limitation
• Antibiotics in renal impairment patients
• Myths in antibiotics

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Dose adjustment in renal impairment
• Reduce/adjust the dose which is excreted through kidney
• If the patient is on hemodialysis 
• give antibiotics after HD as soon as possible;
• dose adjustment is not needed (give full dose);
• Risk of dose adjustment  less efficacy, but consider less toxicity
• Supportive therapy is mandatory  fluid maintenance, nutrition, albumin
level, anemia

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Summary
• Beware of post antibiotic era  died due to MDRO
• Proper usage of AB  use local guideline
• Start the antibiotics with 1st line empirical therapy
• Use the carbapenems for 3rd line empirical therapy or definitive
therapy according to microbiology culture
• Do the proper Laboratory interpretation include leucocytosis and
procalcitonin

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