Transcript urinary tract infection in children

Rational use of antibiotics
in child infection
Marjan Nassiri-Asl
Pharm.D, Ph.D
Qazvin University of Medical Sciences
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Key facts on
inappropriate use of
antibiotics
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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.
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Consequences of inappropriate
antibiotic use
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Antimicrobial resistance
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Adverse drug reactions and medication errors
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Lost resources
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Eroded patient confidence
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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, 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
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Appropriate use of
antibiotics in children
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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?
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Choice of antimicrobial agent
Based on three main factors:
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Etiological agent
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Patient-related factors
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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
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Most probable agents: based on epidemiology and clinical
experience
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Importance of local antibiotic resistance data
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Resistance patterns vary
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From country to country
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From hospital to hospital in the same country
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From unit to unit in the same hospital
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With time
Regional/country data useful only for following trends,
NOT guide empirical therapy
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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
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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
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Antibiotic choice:
Patient-related factors
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Antibiotic choice:
Patient-related factors
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Age
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Physiological factors
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Comorbidoties
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Genetic factors
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Pregnancy
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Site and severity of infection
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Allergies
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Antibiotic choice:
Antibiotic-related factors
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Antibiotic choice:
Antibiotic-related factors
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Pharmacokinetic/pharmacodynamic (PK/PD) profile
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Absorption
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Excretion
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Tissue levels, peak levels, AUC,
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Time above MIC
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Toxicity and other adverse effects
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Drug-drug interactions
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Cost
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PK/PD factors
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Increasing knowledge on the association between
PK/PD parameters on
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Clinical efficacy

Preventing emergence of resistance
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Enables optimization of dosage regimens
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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
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Not just the unit cost of the antibiotic
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Materials for administration of drug
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Labour costs
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Expected duration of stay in hospital
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Cost of monitoring drug levels
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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
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Eliminates risks of complications
associated with intravascular lines
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Shorter duration of hospital stay
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Savings in nursing time
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Savings in overall costs
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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 μg/ml
trough <2 μg/ml
 Vancomycin
Peak= 25-40 μg/ml
trough <10 μg/ml
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Gram negative enteric bacteria
 Ampicillin
 Aminoglycoside

3rd generation cephalosporin (Cefotaxime
or Ceftazidime)
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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 penetration into CNS
3)
Much 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
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It is an essential role of the pediatrician to ensure that
antibiotics are used appropriately
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This is easy! Ask simple questions before initiating any
antimicrobial treatment.
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Be systematic in your approach
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Consider alternatives
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Know the important facts about
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Best schedules and duration for specific infections
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New ways of using old antibiotics
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Availability of new agents and new treatment modalities
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