Rational use of antibiotics in child infection Marjan Nassiri-Asl Pharm.D, Ph.D Qazvin University of...

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Rational use of antibiotics in child

infection

Marjan Nassiri-Asl

Pharm.D, Ph.DQazvin University of Medical Sciences

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Key facts oninappropriate use of

antibiotics

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Inappropriate use of antibioticsis 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

• Antimicrobial resistance • Adverse drug reactions and medication errors• Lost resources• 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 ofantibiotics 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:• 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 laboratoryExample: UTI

How was sample collected?Contamination of sample is frequent,

even in the best conditionsConsider 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

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Examples of local sensitivity issues

E. coliResistance to ampicillin has increased

rapidly in the past ten yearsNow 85% strains are resistant to

ampicillin

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

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Urinary Tract Infection: Clinical Practice Guideline for the Diagnosis and Management of the Initial UTI inFebrile 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

• 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 Important parameter Dosage optimization

Dose-dependent Aminoglycosides, Quinolones

Cmax / MIC Prolonged

PAESingle daily dose

Time-dependent Penicillin, Cephalosporins

T > MIC No PAE

Multiple DD or continuous infusion

Cumulative-dose dependent Clarithromycin, Clindamycin

AUC / MIC Prolonged

PAE

Total dose and duration

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 oral agents

Higher and more persistent serum and tissue levels

For 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 or ceftazidim & aminoglycoside

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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

AmpicillinAminoglycoside 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 & vancomycin-insensitive 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 neonatesNarrow-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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