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Physician related
Lack of knowledge
Delayed lab results, fear of clinical failure
Inappropriate peer norms,
local medical culture
Economic incentives
Patient demand of quick fix
Determinants of irrational use of
antibiotics
Antimicrobial resistance
Time above
MIC
Time
Pharmacodynamic properties of
antibiotics
Type of bactericidal Important
Dosage optimization
profile parameter
Time-dependent Multiple DD or
T > MIC No PAE
Penicillin, cephalosporins continuous infusion
Cumulative-dose
dependent AUC / MIC Total dose and
Clarithromycin, Prolonged PAE duration
clindamycin
Dose-dependent Time-dependent
Aminoglycosides Beta-lactames
Fluoroqinolones Glycopeptides
Metronidazol Macrolides
Amphotericin B Linkozamides
General principles
Clinical assessment
Type of patient
Immune status
AIDS, hematological malignancies ; influence both
the likelihood of an infection and its likely etiology.
Host factors
Presence of prosthetic material
Rarely respond to antibiotic therapy
Usually require removal of device
Allergy
Determination of previous allergic drug reactions,
including antimicrobial agents.
Failure to do so can have catastrophic
consequences.
B) Likely infecting agent
Clinical assessment may allow a likely source
of infection.
Empirical treatment is aimed at these
organisms..
Laboratory investigations supports to establish
a definitive microbiological diagnosis.
Other considerations
Routes of administration:
Parenteral therapy:
Seriously ill patient, where effective drug concentrations are
required rapidly at the site of infection.
Drugs not orally absorbed e.g. aminoglycosides,
glycopeptides
Oral route is contraindicated
Patient usually switched to oral formulation after 48-72
hours.
Oral therapy
Topical
Superficial skin infections, mucosal candidiasis, middle ear
and superficial ocular infections
Dosage regimens
Lowest dose that is effective
Dose influenced by severity of infection, age and
weight of the patient.
Standard treatment guidelines should be followed.
Encouraging compliance
Less frequency improves compliance
Length of treatment
Depends upon site and severity of infections,
causative organisms and patients response to the
treatment.
Combination therapy
High risk of toxicity, interactions
High cost, Less compliance
Useful in
Empirical therapy to cover several pathogens
E.g. Severe community acquired pneumonia; combination
of beta lactam and macrolide is used.
Brain abscesses; ceftriaxone + metronidazole
Treatment of mixed infections
E.g. intra-abdominal infections
Gram negative agent (Ceftriaxone/aminoglycoside) +
Metronidazole (broad spectrum anaerobic) + Amoxycillin
(against enterococci)
Combination therapy
Synergy :
E.g. beta lactams + Aminoglycosides more effective
than penicillin alone in streptococcal endocarditis.
Broadening of antimicrobial activity
Combination of antibiotic + Enzyme inhibitor e.g.
amoxicillin + clavulanic acid.
Inhibitors against human enzymes, to reduce
metabolism of antibiotics. E.g imipenam + cilastin.
Avoiding drug resistance
E.g. quadruple therapy for tuberculosis.
Indifference Synergism Antagonism
Log of number if viable bacteria/mL
Drug A
Drug A
Drug C
Drug B
Drug B
A+ C
A+ B
II III
I A+ B Drug A
Panel discussion
Updates
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