Transcript Appropriate use of antimicrobial agents

Appropriate use of
antimicrobial agents
Dr Olga Perovic,
CMID/NHLS/WITS
2009
Introduction
• Since evolution of antimicrobials
large number of agents are
available.
• But their administration may be
create unnecessary effects:
– Antimicrobial overuse
– Antimicrobial resistance
– Inappropriate use
• No organism identification
• No susceptibility testing
• No host factors taken in consideration
when antimicrobials chosen.
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How to choose the appropriate antimicrobial
agents?
1. The right antibiotic for disease.
2. Antibiotic should have the most narrow
spectrum of activity for particular disease.
3. Administration of antibiotics according to
severity of disease and host factors.
4. To consider the ways that body handles a
drug?
5. To avoid unwanted effects of the drugs?
6. Duration of the treatment.
7. Antibiotic that is less likely to select for
resistance.
8. Antibiotic that cure the patient.
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1. The right antibiotic for disease
• What is needed?
– Consider mechanism of activity.
• Bactricidal activity,
• Bacteriosatic activity.
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What is right direction?
•Bacteriocidal
–Mechanism of action
•Antibiotics break down
cell wall.
•Antibiotics that prevent
DNA synthesis.
•Bacteristatic
–Mechanism of action
•Antibiotics that inhibit
protein synthesis.
•Antibiotics that inhibit
nucleotide synthesis.
•Antibiotics that replace
essential metabolites.
Organisms that are causes of severe disease
such as meningitis, endocarditis should be
treated with bactericicdal agents.
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2. The most narrow activity of
selected antibiotic for disease
• Can we determine right
agent?
– Laboratory testing
• Submit specimen from correct
site of infection.
• Isolate an infectious organism
• Identify and perform.
susceptibility.
• Show serological rising of titer for
disease.
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MIC/MBC and
correlation with disk
diffusion method
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3. How to administer antibiotic?
•Route of
administration
–Oral
–IM
–IV
–Subcutaneus
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•Penetration of
antibiotics at site of
infection in high
concentration.
•Host factors
–Age
–Pregnancy
–Genetic abnormalities
–Renal and hepatic
dysfunction
–Site of infection.
4. What are the ways that body handles a
drug?
•
•
•
•
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Absorption
Distribution
Metabolism
Excretion
Example of absorption of antibiotics from the
gastrointestinal tract
Well absorbed
Poorly absorbed
Not absorbed
Penicillin V
Penicillin G
Aminoglycosides
Amoxicillin
Ampicillin
Vancimycin
Cloxacillin
Methicillin
Carbapenems
Oral cephalosporins:
Cephalexin,
Cefuroxime Cefixime
Cefpodoxime
Quinolone
Chloramphenicol
Azithromycin
Clarithomycin
Erythromycin
Doxicycline
Tetracycline
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5. Duration of treatment
• Short
– To treat as long as is clinically indicated.
Once patient is better to stop treatment.
• Long
– Until organism is eradicated.
– Certain conditions that need long duration:
• Endocarditis
• Cystic fibrosis
• Bone and joint infections.
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6. Unwanted effects
• Special attention for patients
with
– Renal failure.
– Hepatic failure.
– Neutropenic patients.
– Allergy.
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7. Characterization of bacterial resistance to
antibiotics
• Genetics versus parental strain.
• Biochemical (presence or absence of a
resistance mechanism).
• Microbiologic (elevated MIC).
• Clinical (therapeutic outcome).
• Intrinsic (present in all members of a given
genus or species).
• Acquired (present only in certain isolates of
a genus or species).
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Resistance to
antibiotics
ß-lactamases
in gram-negative
ß-lactamases in gram-positive
ß-lactam
PBPs and altered PBP
Efflux pump
Porins
50
30
Permeability
Methylation of the
23S rRNA changes
50S rRNA result is no
binding of macrolides
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Linezolid-mutation
of 23S rRNA gene
specific for S. aureus
and E. faecalis
7. Antibiotics that most likely select for
resistance!
• Antibiotics that causes “collateral
damage”
– Cephalosporins
– Quinolones
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8. What drug does to the body?
• Pharmacodynamic feature of antibiotics.
– An antimicrobial agent may inhibit growth and
replication (static effect) or cause bacterial
cell death (cidal).
– Concentration is important (one antibiotic
may be bacteriosatic at low concentration but
bactericicdal in high concentrations.
• Pharmacodynamics relationships
– Concentration-dependent killing agents
– Time-dependent killing agents
– Activity of antibiotics measured by MIC
(minimum inhibitory concentration).
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AUC/MIC ratio
•Cmax/MIC ratio-the maximum serum
concentration of the drug (Cmax)
divided by the MIC. Predict efficacy and
development of resistance.
AUIC is AUC/MIC ratio- the area
under the 24-hour serum
concentration curve (AUC)
divided by the MIC. A predictor of
bacterial/clinical success.
Cmax and AUC are
covariant: when Cmax
increases, AUC increase
also.
•Time above MIC
(T>MIC). The time
that serum drug
concentrations stay
higher than the MIC
for the organism.
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The pharmacodynamic properties of major
antibiotic groups
Pd
ß-lactams
aminoglycosides
macrolides
fluoroquinolones
Timedependent
killing
+++
+/-
+++
+
Concentration
dependent
killing
+/-
+++
+
+++
Best predictor
of response
Time above
MIC
Cmax/MIC
?
AUIC
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Summary-kill the bug!
• Facts: appropriate therapy saves lives!
• Actions:
– Diagnose and identify the etiologic agent
– Culture the patient’s specimen(s).
– Target EMPIRIC therapy to likely pathogens
based on hospital antibiogram.
– Target DEFINITIVE therapy based to accurate
identification of organism/s and susceptibility
(MIC) RESULTS.
– Monitor therapy outcome.
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