Rational use of antibiotics

in child infection
Marjan Nassiri-Asl
Pharm.D, Ph.D
Qazvin University of Medical Sciences
1

Key facts on
inappropriate use of
antibiotics

Inappropriate use of antibiotics

is a worldwide problem

More than 50% of all medicines are prescribed, dispensed or sold

inappropriately, and half of all patients fail to take medicines correctly.

The overuse, underuse or misuse of medicines harms people and

wastes resources.

More than 50% of all countries do not implement basic policies to

promote rational use of medicines.

In developing countries, less than 40% of patients in the public sector

and 30% in the private sector are treated according to clinical
guidelines.

Consequences of inappropriate
antibiotic use

Antimicrobial resistance

Adverse drug reactions and medication errors

Lost resources

Eroded patient confidence

Principles of antibiotic therapy

Antibacterial therapy in infants and children
presents many challenges:
1)

A daunting problem is the paucity of

pediatric data regarding pharmacokinetics
and optimal dosages
Pediatrics

recommendations are therefore

extrapolated from studies in adults
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Principles of antibiotic therapy

Antibacterial therapy in infants and children presents many
challenges:
2)

The need for the clinician to consider important

differences among various age groups with respect to the
pathogenic species responsible for pediatric bacterial
infections
Age-appropriate

antibiotic dosing and toxicities must also

be considered, taking into account the developmental
status and physiology of infants and children

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Principles of antibiotic therapy

Antibacterial therapy in infants and children
presents many challenges:
3)

The style of usage of antibiotics has some

important differences compared with usage in
adult patients

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Principles of antibiotic therapy

Specific

antibiotic therapy is optimally driven by a

microbiological diagnosis,
diagnosis predicted on isolation
of the pathogenic organism from a sterile body
site, and supported by antimicrobial susceptibility
testing

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Principles of antibiotic therapy

Given

the inherent difficulties that can arise in

collecting specimens from pediatric patients and
given the increased risk of serious bacterial
infection in young infants

Much

of pediatric infectious diseases practice is

based on a clinical diagnosis with empirical use of
antibacterial agents before or even without
eventual identification of the specific pathogen

14

Appropriate use of
antibiotics in children

15

Considerations before prescribing

1.

Is an antibiotic necessary?

2.

What is the most appropriate antibiotic?

3.

What dose, frequency, route and duration?

4.

How to improve the chances that the

tretament will be effective?

16

Choice of antimicrobial agent

Based on three main factors:
Etiological

agent

Patient-related

factors

Antibiotic-related

factors

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Antibiotic choice:
Etiological agent
Be

careful of the identification of the agent by the laboratory

Example:
How

UTI

was sample collected?

Contamination

of sample is frequent, even in the best

conditions
Consider

the symptoms

Consider

the urinalysis

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Antibiotic choice: Etiological agent

Most probable agents: based on epidemiology and clinical

experience

Importance of local antibiotic resistance data

Resistance patterns vary

From country to country

From hospital to hospital in the same country

From unit to unit in the same hospital

With time

Regional/country data useful only for following trends, NOT guide

empirical therapy

19

Examples of local sensitivity issues

E.

coli

Resistance

to ampicillin has increased

rapidly in the past ten years

Now

85% strains are resistant to ampicillin

20

Pediatrics 2011:128(3):595
www.pediatrics.org/cgi/doi/10.1542/peds.2011-1330

Urinary Tract Infection: Clinical Practice Guideline for the Diagnosis and Management of
the Initial UTI in Febrile Infants and Children 2 to 24 Months. Pediatrics 2011:128(3):595

Urinary Tract Infection: Clinical Practice Guideline for the Diagnosis and Management of the Initial UTI in
Febrile Infants and Children 2 to 24 Months. Pediatrics 2011:128(3):595
22

Antibiotic choice:
Patient-related factors

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Antibiotic choice:
Patient-related factors

Age

Physiological factors

Comorbidoties

Genetic factors

Pregnancy

Site and severity of infection

Allergies

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Antibiotic choice:
Antibiotic-related factors

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Antibiotic choice:
Antibiotic-related factors

Pharmacokinetic/pharmacodynamic (PK/PD) profile

Absorption

Excretion

Tissue levels, peak levels, AUC,

Time above MIC

Toxicity and other adverse effects

Drug-drug interactions

Cost

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PK/PD factors

Increasing knowledge on the association between PK/PD parameters

on

Clinical efficacy

Preventing emergence of resistance

Enables optimization of dosage regimens

In some instances this has led to a redefinition of interpretative

breakpoints in sensitivity testing

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Pharmacodynamic properties of antibiotics

Type of bactericidal profile
Dose-dependent

Aminoglycosides, Quinolones

Time-dependent
Penicillin, Cephalosporins

Cumulative-dose dependent
Clarithromycin, Clindamycin

Important
parameter

Dosage optimization

Cmax / MIC
Prolonged
PAE

Single daily dose

T > MIC
No PAE

Multiple DD or
continuous infusion

AUC / MIC
Prolonged
PAE

Total dose and

duration

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PAE: Post-Antibiotic Effect

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Antibiotic choice:
Antibiotic-related factors: Cost

Not just the unit cost of the antibiotic

Materials for administration of drug

Labour costs

Expected duration of stay in hospital

Cost of monitoring drug levels

Expected compliance
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Choice of regimen

Oral vs parenteral
Traditional

view

serious

= parenteral

Previous

lack of broad spectrum oral antibiotics with

reliable bioavailability

Improved
Higher
For

oral agents
and more persistent serum and tissue levels

certain infections as good as parenteral

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Advantages of oral treatment

Eliminates risks of complications associated with

intravascular lines

Shorter duration of hospital stay

Savings in nursing time

Savings in overall costs

Greater patient satisfaction

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Necrotic skin lesions

Suggestion

of Pseudomonas infection

Piperacillin, Ticarcillin
aminoglycoside

or

ceftazidim

&

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Treatment
Some

experts
recommend
antifungal
prophylaxis with fluconazole for particulary
high risk newborns)

LBW<1 kg, low gestational age <27 wk

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Attention!!
Peak

and trough are useful to ensure

therapeutic levels and minimize toxicity if the
agent is administrated for more than 2-3 days

Gentamicin

Peak= 5-10 g/ml

trough <2 g/ml

Vancomycin

Peak= 25-40 g/ml

trough <10 g/ml

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Gram negative enteric bacteria

Ampicillin
Aminoglycoside

3rd generation cephalosporin (Cefotaxime

or Ceftazidime)

37

Treatment of enterocci
Penicillin

(Ampicillin or Piperacillin)+ Aminoglycoside

Synergy

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Treatment anaerobic infections

Clindamycin
Metronidazole

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Treatment of neonatal sepsis & meningitis

3rd generation of cephalosporins (Cefotaxime)
1)MIC

cephalosporins (g_ enteric bacilli)< Aminoglycoside

2)Excellent
3)Much

penetration into CNS

higher doses can be given

4)(However, inappropriate

for suspected sepsis in NICU

patients)

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Vancomycin
The

emergence of antibiotic resistance among

pathogens that infect newborns is of great concern

Vancomycin-resistant

enterococci & vancomycininsensitive S. aureus are worrisome

Guideline

to limit the use of vancomycin must be

followed

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Treatment
Methicillin-resistant S. aureus when endemic in neonatal units

Vancomycin (empirical therapy)

High suspicion of severe infection with coagulase-negative staphylocci

Blood culture negative

Discontinuing therapy

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Rational use of antibiotics in neonates

Narrow-spectrum

drugs when possible,

treating infection & not colonization, and
limiting the duration of therapy

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In conclusion

It is an essential role of the pediatrician to ensure that

antibiotics are used appropriately

This is easy! Ask simple questions before initiating any

antimicrobial treatment.

Be systematic in your approach

Consider alternatives

Know the important facts about

Best schedules and duration for specific infections

New ways of using old antibiotics

Availability of new agents and new treatment modalities

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