Antimicrobial dosing regimens historically have been based on the premise that serum
concentrations must be higher than the minimum inhibitory concentration (MIC) of the
antimicrobial against the pathogen. However, the relationship between serum concentrations
and bacterial eradication has only recently been clearly defined, and MICs of some
pathogens that are regarded as susceptible to some antimicrobial agents are actually
higher than peak serum concentrations of these agents. Although the MIC is an important
measure of antimicrobial activity, it does not take into account patient-, drug-,
and pathogen-related factors that influence the outcome of antimicrobial therapy.
Increasing pathogen resistance and documented treatment failures, particularly in
respiratory tract infections, indicate a need to reevaluate dosing strategies with
available agents to maximize antimicrobial effectiveness and limit the spread of resistance.
It is now understood that to achieve bacteriologic and clinical success, sufficient
concentrations of antimicrobial at the site of infection must be maintained for an
adequate period of time. These dynamics are determined by combining drug pharmacokinetic
and pharmacodynamic (PK/PD) data with MIC data. Different classes of antimicrobials
have different patterns of bactericidal action based on pharmacokinetic and pharmacodynamic
characteristics, and these patterns influence antimicrobial efficacy. PK/PD characteristics
of an antimicrobial need to be integrated with MIC data to guide dosing strategies
and predict bacteriologic and clinical outcomes. This approach not only improves antimicrobial
efficacy but also serves to limit development of further pathogen resistance.
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