Review article| Volume 24, ISSUE 2, P477-502, June 2004

Application of pharmacokinetics and pharmacodynamics to antimicrobial therapy of respiratory tract infections

      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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