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Applying Pharmacodynamics for Susceptibility Breakpoint Selection 37TABLE 5 PK–PD Targets Derived from Animal Infection Models and Clinical DataDisease state Drug Clinically derived PK–PD targetHospital-acquiredpneumoniaCommunityacquiredrespiratory tractinfectionsAnimal infection model;organism studiedQuinolones fAUC0–24:MIC ratio: 62–75 Neutropenic mouse-thigh;gram-negative bacilliQuinolones fAUC 0–24 :MIC ratio: 34 Immunocompetent mousethigh;Streptococcuspneumoniaeb-lactams T>MIC: 40% of thedosing intervalImmunocompetent mousethigh;S. pneumoniaeTelithromycin AUC 0–24 :MIC ratio: 3.375 Neutropenic mouse-thigh;S. pneumoniaeBacteremia Oritavancin fT >MIC :22% of the dosinginterval for StaphylococcusaureusComplicated skinand skin structureinfectionsLinezolid AUC0–24:MIC ratio: 85 forS. aureus or EnterococcusfaeciumNeutropenic mouse-thigh;S. aureusNeutropenic mouse-thigh;S. aureusTigecycline AUC0–24:MIC ratio: 17.9 Neutropenic mouse-thigh;S. aureusLinezolid AUC0–24:MIC ratio: 110 Neutropenic mouse-thigh;S. aureusAnimal-derived PK–PDtargetfAUC0–24:MIC ratio: 70–90for 90% animal survivalor two log-unit killfAUC 0–24 :MIC ratio: 25–34for 90% animal survivalor 2 log-unit killT>MIC: 30–40% of thedosing interval for 90%animal survivalAUC 0–24 :MIC ratio: 1000for stasisfT >MIC : 20% of the dosinginterval for a 0.5 log-unitkillAUC0–24:MIC ratio: 83 forstasisAUC0–24:MIC ratio: 20 forstasisAUC0–24:MIC ratio: 83 forstasisAbbreviations: AUC, area under the concentration–time curve at 24 hours; MIC, minimum inhibitory concentration; PD, pharmacodynamic; PK, pharmacokinetic; T >MIC , durationof time the drug concentration remains above the MIC value.