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I - Selection of Antimicrobial Chemotherapy, III - Determinants of…
I - Selection of Antimicrobial Chemotherapy
A) Identification of the Organism
B) Empiric Antimicrobial Therapy
timing
selecting a drug
C) Determination of antimicrobial susceptibility
Bactericidal vs bacteriostatic
Minimum inhibitory concentration (MIC)
Minimum bactericidal concentration (MBC)
D) Site of infection - BBB
lipid solubility
- Chloramphenicol & Metronidazole are lipid soluble
Beta lactams are ionized at physiological pH & do not cross BBB unless it is inflamed
Molecular weight
- vancomycin has high molecular weight & does not penetrate even inflamed meninges
Protein binding
Efflux pumps & transporters
E) Patient Factors
Immune system
Renal dysfunction
: vancomycin & aminoglycosides are nephrotoxic
Hepatic dysfunction
: erythromycin & doxycycline must be used with caution in liver damage
Poor perfusion
: Eg. diabetic foot
Age
: neonates are vulnerable to toxicity from chloramphenicol, sulfonamides
Pregnancy & lactation
: Eg. tetracyclines, aminoglycosides, FQs are teratogenic
Risk for MDR organism
: prior antimicrobial therapy or hospitalization in preceding 90 days, current hospitalization > 5 days, resistance in local antibiograms, immunosuppression
G) Safety of the agent
H) Cost of therapy
III - Determinants of Rational Dosing
Concentration dependent killing
significant increase in the rate of bacterial killing as the concentration of antibiotic increases from 4- to 64-fold the MIC of the drug for the infecting organism
Eg. aminoglycosides, FQs, metronidazole, daptomycin
TIme dependent killing
clinical efficacy is predicted by the percentage of time that blood concentrations of the antimicrobial remains above the MIC.
Eg. beta lactams, macrolides
Post Antibiotic effect
persistent suppression of microbial growth that occurs after levels of antibiotic have fallen below the MIC
Eg. FQs, aminoglycosides
AUC24/MIC
combination of concentration & time
Eg. FQs, vancomycin
IV - Chemotherapeutic Spectra
Narrow Spectrum
Extended Spectrum
Broad Spectrum
II - Route of Administration
V - Combinations of Antimicrobials
VI - Antimicrobial Resistance