In vitro and in vivo pharmacokinetic/pharmacodynamic activity of clofoctol.

The aim of the study was to examine the In vitro susceptibility of clinical isolates of respiratory pathogens to clofoctol compared with amoxicillin and erythromycin, and to characterize the pharmacokinetic/pharmacodynamic (PK/PD) relationships of clofoctol using a murine pneumonia infection model. Strains clinically isolated from patients between 2005 and 2009 were used to examine susceptibility: penicillin-susceptible Streptococcus pneumoniae, penicillin-resistant S. pneumoniae, Streptococcus pyogenes, methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus, and Haemophilus influenzae. The In vitro activity of clofoctol against clinical isolates has essentially remained unchanged over recent years. The MIC50 and MIC90 of clofoctol against penicillin-resistant S. pneumoniae are lower than that of amoxicillin and erythromycin. The area under curve/minimum inhibitory concentration (AUC/MIC) ratio is the PK/PD parameter that best correlates with in vivo clofoctol efficacy; the value of AUC/MIC required to achieve the maximum effect in this study was 75.5.

Pharmacokinetics/pharmacodynamics of antibacterials in the Intensive Care Unit: setting appropriate dosing regimens.

Patients admitted to Intensive Care Units (ICUs) are at very high risk of developing severe nosocomial infections. Consequently, antimicrobials are among the most important and commonly prescribed drugs in the management of these patients. Critically ill patients in ICUs include representatives of all age groups with a range of organ dysfunction related to severe acute illness that may complicate long-term illness. The range of organ dysfunction, together with drug interactions and other therapeutic interventions (e.g. haemodynamically active drugs and continuous renal replacement therapies), may strongly impact on antimicrobial pharmacokinetics in critically ill patients. In the last decade, it has become apparent that the intrinsic pharmacokinetic (PK) and pharmacodynamic (PD) properties are the major determinants of in vivo efficacy of antimicrobial agents. PK/PD parameters are essential in facilitating the translation of microbiological activity into clinical situations, ensuring a successful outcome. In this review, we analyse the typical patterns of antimicrobial activity and the corresponding PK/PD parameters, with a special focus on a PK/PD dosing approach of the antimicrobial agent classes commonly utilised in the ICU setting.

Influence of pharmacokinetics/pharmacodynamics of antibacterials in their dosing regimen selection.

The choice of antimicrobial dosing in clinical practice in the past was based upon a 'penicillin mentality', that is, on the assumption that the in vivo antimicrobial efficacy is dependent on the duration of drug levels above the minimum inhibitory concentration of target microorganisms. Really, a rational antimicrobial therapy is strongly related to a basic understanding of the influence the patient has on the antibiotic (pharmacokinetics [PKs]) and the patient's response to the specific drug effects (pharmacodynamics [PDs]). PK/PD parameters are essential in facilitating the translation of microbiological activity into clinical situations, ensuring a successful outcome. This review will analyze the typical patterns of antimicrobial activity and the corresponding PK/PD parameters, with a special focus on a PK/PD dosing approach with the most commonly utilized antimicrobial agent classes.