Clinical Use Of Pharmacokinetics And Pharmacodynamics

Knowledge of pharmacodynamics has had a remarkable impact on the clinical use and regulatory development of antimicrobials. For example, the ability to predict efficacy against both drug-susceptible and -resistant pathogens based on achieving a defined pharmacodynamic target has been useful in the design of treatment strategies in the face of emerging antimicrobial drug resistance. This impact has been most evident in prediction of treatment outcome against increasing multidrug-resistant S. pneumoniae (6,13,14,16,41,51). Although there are numerous beta-lactam antibiotics approved for the treatment of pneumococcal respiratory tract infections, in the face of resistant pneumococci, pharmacodynamic analysis would predict treatment failure for many of the antibiotics included in this group. The elevation in MIC reduces the %T>MIC for all available oral cephalosporins well below the 40% target, and treatment failure would be anticipated (13,16,51). These predictions have been confirmed in studies of patients with both community-acquired pneumonia and upper respiratory tract infection (12,35-37,41). This type of pharmacodynamic knowledge has been used to develop treatment guidelines for otitis media, sinusitis, and community-acquired pneumonia, and these differences in pharmacodynamic potency are reflected in recent recommendations (13,14,16). In addition, these approaches to understanding antimicrobial efficacy have been used to determine the MIC levels for which organisms should be labeled susceptible or resistant, termed susceptibility breakpoints (10,52).

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