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

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

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)	· AUC_0-24/MIC ≥25*
Echinocandin antifungals (caspofungin, micafungin, anidulafungin)	Sample B: mid-way through dosing interval (50% of dosing interval)	· AUC_0-24/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*
		· AUC_0-24/MIC ≥350

* denotes the primary endpoint – other stated pharmacodynamics targets are secondary endpoints.
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); AUC_0-24/MIC is the ratio of the area under the concentration time curve from 0–24 hours to MIC.