Population Pharmacokinetics of Piperacillin following Continuous Infusion in Critically Ill Patients and Impact of Renal Function on Target Attainment

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Fältnamn	Indikatorer	Metadata
000		03855naa a2200457 4500
001		oai:DiVA.org:uu-408727
003		SwePub
008		200413s2020 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4087272 URI
024	7	a https://doi.org/10.1128/AAC.02556-192 DOI
040		a (SwePub)uu
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Klastrup, Vibeke4 aut
245	1 0	a Population Pharmacokinetics of Piperacillin following Continuous Infusion in Critically Ill Patients and Impact of Renal Function on Target Attainment
264	1	c 2020
338		a print2 rdacarrier
500		a Title in thesis list of papers: Population pharmacokinetics of piperacillin following continuous infusion in critically ill patients: Impact of renal function on target attainment
520		a Pharmacokinetic changes are often seen in patients with severe infections. Administration by continuous infusion has been suggested to optimize antibiotic exposure and pharmacokinetic/pharmacodynamic (PK/PD) target attainment for β-lactams. In an observational study, unbound piperacillin concentrations (n = 196) were assessed in 78 critically ill patients following continuous infusion of piperacillin-tazobactam (ratio 8:1). The initial dose of 8, 12, or 16 g (piperacillin component) was determined by individual creatinine clearance (CRCL). Piperacillin concentrations were compared to the EUCAST clinical breakpoint MIC for Pseudomonas aeruginosa (16 mg/liter), and the following PK/PD targets were evaluated: 100% free time (fT) > 1× MIC and 100% fT > 4× MIC. A population pharmacokinetic model was developed using NONMEM 7.4.3 consisting of a one-compartment disposition model with linear elimination separated into nonrenal and renal (linearly increasing with patient CRCL) clearances. Target attainment was predicted and visualized for all individuals based on the utilized CRCL dosing algorithm. The target of 100% fT > 1× MIC was achieved for all patients based on the administered dose, but few patients achieved the target of 100% fT > 4× MIC. Probability of target attainment for a simulated cohort of patients showed that increasing the daily dose by 4-g increments (piperacillin component) did not result in substantially improved target attainment for the 100% fT > 4× MIC target. To conclude, in patients with high CRCL combined with high-MIC bacterial infections, even a continuous infusion (CI) regimen with a daily dose of 24 g may be insufficient to achieve therapeutic concentrations.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Infektionsmedicin0 (SwePub)302092 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Infectious Medicine0 (SwePub)302092 hsv//eng
653		a beta-lactam antibiotic
653		a continuous infusion
653		a critically ill
653		a pharmacokinetics
653		a piperacillin
653		a Farmaceutisk farmakologi
653		a Pharmaceutical Pharmacology
653		a Klinisk farmakologi
653		a Clinical Pharmacology
700	1	a Thorsted, Andersu Uppsala universitet,Institutionen för farmaceutisk biovetenskap4 aut0 (Swepub:uu)andth549
700	1	a Storgaard, Merete4 aut
700	1	a Christensen, Steffen4 aut
700	1	a Friberg, Lenau Uppsala universitet,Institutionen för farmaceutisk biovetenskap4 aut0 (Swepub:uu)lenasimo
700	1	a Öbrink-Hansen, Kristina4 aut
710	2	a Uppsala universitetb Institutionen för farmaceutisk biovetenskap4 org
773	0	t Antimicrobial Agents and Chemotherapyg 64:7q 64:7x 0066-4804x 1098-6596
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-408727
856	4 8	u https://doi.org/10.1128/AAC.02556-19

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Av författaren/redakt...: Klastrup, Vibeke; Thorsted, Anders; Storgaard, Meret ...; Christensen, Ste ...; Friberg, Lena; Öbrink-Hansen, K ...

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