Right Dose Right Now: bedside data-driven personalized antibiotic dosing in severe sepsis and septic shock — rationale and design of a multicenter randomized controlled superiority trial

Table 1 Antibiotic pharmacometric targets

Antibiotic	Pharmacokinetic model	AutoKinetics dosing target	Routine practice at Amsterdam UMC, location VUmc	Routine practice at OLVG Oost
Ceftriaxone	Garot et al., 2011 [19]	100%T > 4 × MIC	2000mg every 24 h	2000mg every 24 h
Meropenem	Muro et al., 2011 [20]	100%T > 4 × MIC	1000mg every 8 h	1000mg every 8 h
Ciprofloxacin	Khachman et al., 2011 [21]	AUC0–24/MIC > 125	400mg every 8 h	400mg every 12 h
Vancomycin	Roberts al., 2011 [22]	AUC0–24/MIC > 400	1000mg every 24 h + TDM	1000mg every 24 h + TDM

Pharmacometric models, dosing targets and routine dosing for the study antibiotics. All model parameters were calibrated prior to implementation. For meropenem and ciprofloxacin, routine dosing includes a dose reduction by 50% and an increased dosing interval to 2dd if the estimated glomerular filtration rate is less than 30 ml/min/1.73 m². For vancomycin, routine dosing includes dose adaptation using therapeutic drug monitoring after 1–3 days at Amsterdam UMC, location VUmc and after every 24 h at OLVG Oost. Vancomycin is administered by continuous infusion at OLVG Oost
AUC area under the time–concentration curve, MIC minimal inhibitory concentration, TDM therapeutic drug monitoring, 100%T hundred percent of time

ISSN: 1745-6215