Population Pharmacokinetics and Dosing Optimization of Piperacillin-Tazobactam in Critically Ill Patients on Extracorporeal Membrane Oxygenation and the Influence of Concomitant Renal Replacement Therapy

Hahn, Jongsung; Min, Kyoung Lok; Kang, Soyoung; Yang, Seungwon; Park, Min Soo; Wi, Jin; Chang, Min Jung

doi:10.1128/SPECTRUM.00633-21

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Population Pharmacokinetics and Dosing Optimization of Piperacillin-Tazobactam in Critically Ill Patients on Extracorporeal Membrane Oxygenation and the Influence of Concomitant Renal Replacement Therapy

Hahn, Jongsung;
Min, Kyoung Lok;
Kang, Soyoung;
Yang, Seungwon;
Park, Min Soo;
... Wi, Jin;
외 1명

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초록

Critical illness and extracorporeal circulation, such as extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT), may alter the pharmacokinetics of piperacillin-tazobactam. We aimed to develop a population pharmacokinetic model of piperacillin-tazobactam in critically ill patients during ECMO or CRRT and investigate the optimal dosage regimen needed to achieve $90$ 60 mL/min, and at least 12, 16, and 20 g/day was required for CrCL of,40, 40 to 60, and 60 to 90 mL/min, respectively, regardless of ECMO or CVVHDF. In patients with CrCL of $90 m L / min, e v e na co n t in u o u s in f u s i o n o f 24 g / d a y w a s in s u f f i c i e n tt o a c hi e v e a d e q u a t e P T A . T h er e f or e, f u r t h er r ese a r c h o n p er mi ss ib l e hi g h co n t in u o u s in f u s i o n d ose f oc u se d o n t h er i s k o f t o x i c i t y i sr e q u i r e d . (T hi s t r ia l ha s b ee n r e g i s t er e d a tC l ini c a l T r ia l s . g o v u n d er r e g i s t r a t i o nn o . N C T 02581280, D ece mb er 1, 2014.) I M P O R T A N C E T o t h e b es t o f o u r k n o w l e d g e, t hi s i s t h e f i r s tl a r g e p r os p ec t i v e p ha r ma co k in e t i c / p ha r ma co d y nami c (P K / P D) s t u d y o f p i p er a c i l l in - t a z o ba c t amin E C M O p a t i e n t s . W e u se d p i p er a c i l l in - t a z o ba c t am pl a s ma co n ce n t r a t i o n d a t a f r o m f o u r d i f f er e n t c a ses (co n co mi t an t u seo f E C M O an d C V V H D F, r ece i v in g E C M O o n l y, w e an e df r o m E C M O an d r ece i v in g C V V H D F, an d w e an e df r o m E C M O an d n o t r ece i v in g C V V H D F) t o p r o v i d e p r e l imina r y in s i g h t s in t o t h e in cr e m e n t a l e f f ec t so f cr i t i c a l i l l n ess, E C M O, an d C V V H D F o n P K . O u r ana l y s i sr e v e a l e d t ha t v o l u m eo f d i s t r ib u t i o nin cr e a se d in p a t i e n t so n C V V H D F an d c l e a r an ce d ecr e a se dd u r in g E C M O an d a scr e a t inin ec l e a r an ce w a sr e d u ce d . W h e n t a r g e t in g 100$ 60 mL/min, regardless of ECMO or CVVHDF.

키워드

PTA; continuous renal replacement therapy; creatinine clearance; extracorporeal membrane oxygenation; pharmacodynamics; pharmacokinetics; piperacillin; tazobactam; INFECTIONS; PHARMACODYNAMICS; CLEARANCE; LACTAMS; IMPACT; RISK

제목: Population Pharmacokinetics and Dosing Optimization of Piperacillin-Tazobactam in Critically Ill Patients on Extracorporeal Membrane Oxygenation and the Influence of Concomitant Renal Replacement Therapy

저자: Hahn, Jongsung; Min, Kyoung Lok; Kang, Soyoung; Yang, Seungwon; Park, Min Soo; Wi, Jin; Chang, Min Jung

DOI: 10.1128/SPECTRUM.00633-21

발행일: 2021-12

유형: Article

저널명: Microbiology spectrum

권: 9

호: 3