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Table 1 Study drugs, routes of administration, pharmacokinetic/pharmacodynamic targets and blood sampling

From: DALI: Defining Antibiotic Levels in Intensive care unit patients: a multi-centre point of prevalence study to determine whether contemporary antibiotic dosing for critically ill patients is therapeutic

Study Drugs and method of infusion Pharmacokinetic Sampling Pharmacodynamic Targets tested
Beta-lactam antibiotics by intermittent infusion Sample A: mid-way through dosing interval (50% of dosing interval) · 50% f T>MIC
(amoxycillin-clavulanate; ampicillin; piperacillin-tazobactam; penicillin-G; flucloxacillin; dicloxacillin; cloxacillin; cephazolin; ceftazidime; ceftriaxone; cefepime; meropenem; imipenem; doripenem; ertapenem) Sample B: within 30 min of next dose (100% of dosing interval) · 50% f T>4xMIC*
Glycopeptide antibiotics by intermittent infusion (vancomycin, teicoplanin)   · 100% f T>MIC
   · 100% f T>4xMIC
   · 100% f T>4xMIC
   · Concentration ≥15 mg/L*
Triazole antifungals (fluconazole, voriconazole) Sample A: 30 min after completion of intravenous infusion (peak concentration) · AUC0-24/MIC ≥25*
Echinocandin antifungals (caspofungin, micafungin, anidulafungin) Sample B: mid-way through dosing interval (50% of dosing interval) · AUC0-24/MIC ≥20*
  Sample C: within 30 min of next dose (100% of dosing interval)  
Beta-lactam antibiotics (listed above) by continuous infusion Sample A: at any time · 100% f T>4xMIC*
  Sample B: >6 hours after sample A  
Glycopeptide antibiotics (listed above) by continuous infusion   · 100% f T>4xMIC*
   · AUC0-24/MIC ≥350
  1. * denotes the primary endpoint – other stated pharmacodynamics targets are secondary endpoints.
  2. f T>MIC is the duration of a dosing interval for which the antibiotic concentration remains above the minimum inhibitory concentration (MIC) of the known or suspected pathogen (endpoints of 50% or 100% of the interval, and MIC is defined by EUCAST MIC90 data); f T>4xMIC is the duration of a dosing interval for which the antibiotic concentration remains above a concentration that is 4 x the MIC of the known or suspected pathogen (endpoints of 50% or 100% of the interval, and MIC is defined by EUCAST MIC90 data); AUC0-24/MIC is the ratio of the area under the concentration time curve from 0–24 hours to MIC.