HOW TO ASSURE THE MOST APPROPRIATE DOSAGE OF ANTIMICROBIAL DRUGS
Abstract
Background. The final response of a patient to
antimicrobial treatment depends on a number of different
variables. The use of susceptibility endpoints with respect to
the antibiotic concentrations achievable in vivo represents the
conventional approach to clinical dosing of antimicrobial
agents, i.e. by maintaining concentrations above the minimum
inhibitory concentration (MIC). Results from animal and clinical
studies have shown that it is not necessary to fulfil this
condition.
Clinical experience has shown that the success of antimicrobial
drugs which inhibit the synthesis of cell wall (betalactams),
depends on time when concentrations of drugs exceed MIC. In
drugs which inhibit the synthesis of proteins (aminoglycosides),
it is more important to achieve as high peak concentrations
in plasma as possible. Fluoroquinolones inhibit the synthesis
of nucleic acids and may show both types of kinetics.
Conclusions. Considering the microbiological and pharmacokinetic
criteria we can predict which antimicrobial drug
and what dosage regimen is the most appropriate. On the
basis of the literature data we proposed markers to enhance
the prediction of clinical outcomes, e.g. time for which
drug plasma concentration exceeds MIC (t > MIC), ratio between
peak plasma concentration of antimicrobial drug and MIC
(Cmax /MIC) and area under the inhibitory curve (AUIC).
With proper employment of markers for the prediction of the
effect of an antimicrobial drug we contribute to more successful
and rational use and, probably, to a slower development of
resistant organisms.
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