β-Lactam pharmacokinetics during extracorporeal membrane oxygenation therapy: A case–control study

Donadello, Katia; Antonucci, Elio; Cristallini, Stefano; Roberts, Jason A.; Beumier, Marjorie; Scolletta, Sabino; Jacobs, Frédérique; Rondelet, Benoît; Backer, Daniel De; Vincent, Jean‐Louis; Taccone, Fabio Silvio

doi:10.1016/j.ijantimicag.2014.11.005

Cited by 91 publications

(90 citation statements)

References 27 publications

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“…Even a trend for a slightly lower volume of distribution has been reported for meropenem and azithromycin (22,24). In addition, no significant impact of the patients' creatinine clearance (CL CR ) on the teicoplanin CL was found in our study.…”

Section: Discussioncontrasting

confidence: 64%

“…Moreover, since the previous studies were mostly conducted in neonates or an ex vivo system, the same findings may not be applicable to adult patients in our study. In fact, studies involving adult ECMO patients demonstrated no significant alterations in the PK of oseltamivir, piperacillin-tazobactam, and tigecycline (20)(21)(22). For vancomycin, an- a The C trough target was set at Ͼ10 g/ml for mild to moderate infections and Ͼ15 g/ml for severe infections.…”

Section: Discussionmentioning

confidence: 99%

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Population Pharmacokinetics and Dose Optimization of Teicoplanin during Venoarterial Extracorporeal Membrane Oxygenation

Noh

Min

et al. 2017

Antimicrob Agents Chemother

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The pharmacokinetics (PK) of drugs are known to be significantly altered in patients receiving extracorporeal membrane oxygenation (ECMO). However, clinical studies of the PK of drugs administered during ECMO are scarce, and the proper dosing adjustment has yet to be established. We developed a population PK model for teicoplanin, investigated covariates influencing teicoplanin exposure, and suggested an optimal dosing regimen for ECMO patients. Samples for PK analysis were collected from 10 adult patients, and a population PK analysis and simulations were performed to identify an optimal teicoplanin dose needed to provide a Ͼ50% probability of target attainment at 72 h using a trough concentration target of Ͼ10 g/ml for mild to moderate infections and a trough concentration target of Ͼ15 g/ml for severe infections. Teicoplanin was well described by a two-compartment PK model with first-order elimination. The presence of ECMO was associated with a lower central volume of distribution, and continuous renal replacement therapy (CRRT) was associated with a higher peripheral volume of distribution. For mild to moderate infections, an optimal dose was a loading dose (LD) of 600 mg and a maintenance dose (MD) of 400 mg for ECMO patients not receiving CRRT and an LD of 800 mg and an MD of 600 mg for those receiving CRRT. For severe infections, an optimal dose was an LD of 1,000 mg and an MD of 800 mg for ECMO patients not receiving CRRT and an LD of 1,200 mg and an MD of 1,000 mg for those receiving CRRT. In conclusion, doses higher than the standard doses are needed to achieve fast and appropriate teicoplanin exposure during ECMO. (This study has been registered at ClinicalTrials.gov under identifier NCT02581280.)

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Section: Discussioncontrasting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics and Dose Optimization of Teicoplanin during Venoarterial Extracorporeal Membrane Oxygenation

Noh

Min

et al. 2017

Antimicrob Agents Chemother

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“…While some studies suggest a significant loss of meropenem within the ECMO circuit [6, 33, 34], other investigations have found no effect in vivo compared to other critically ill patients [35]. A recent retrospective, case‐control study observed no differences in pharmacokinetic paramenters with either piperacillin/tazobactam or meropenem in patients receiving ECMO compared to those not receiving ECMO [35]. Of interest, nearly 30% of all drug levels measured for the two aformentioned drugs were subtherapeutic, which may be a consequence of other pathophysiological disturbances not controlled for in this critically ill population [35].…”

Section: Antimicrobialsmentioning

confidence: 99%

“…A recent retrospective, case‐control study observed no differences in pharmacokinetic paramenters with either piperacillin/tazobactam or meropenem in patients receiving ECMO compared to those not receiving ECMO [35]. Of interest, nearly 30% of all drug levels measured for the two aformentioned drugs were subtherapeutic, which may be a consequence of other pathophysiological disturbances not controlled for in this critically ill population [35]. Mechanical circulatory support in general can induce a systemic inflammatory response, independent of the underlying critical illness, which, in turn, may augment renal clearance.…”

Section: Antimicrobialsmentioning

confidence: 99%

Medicating patients during extracorporeal membrane oxygenation: the evidence is building

2017

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“…These interventions may influence antibiotic dosing requirements as critically ill patients with CRRT and SLED were reported to have variable antibiotic CL [138][139][140][141][142]. There is limited data on the influence of ECMO [141,[143][144][145][146].…”

Section: Extra-corporeal Circuitsmentioning

confidence: 99%

Optimizing beta-lactam antibiotic dosing in critically ill patients: Prolonged infusion versus intermittent bolus administration

Abdul‐Aziz¹,

Mohd²

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Severe sepsis is a major burden in the intensive care unit (ICU) with persistently high mortality rates. Optimization of antibiotic dosing has been suggested as an intervention to improve clinical outcomes for critically ill patients with severe sepsis. However, current antibiotic dosing guidelines may not be appropriate for these patients, as they rarely consider the altered physiology and illness severity associated with this population. Optimizing antibiotic dosing using pharmacokinetic (PK) and pharmacodynamic (PD) principles can address these critical illness-related changes and promote therapeutic success. Due to their wide spectrum of antibiotic activity and excellent safety profile, beta-lactam antibiotics are commonly used for severe infections in the ICU. Two alternative dosing approaches to traditional intermittent bolus (IB) dosing, namely continuous infusion (CI) and extended infusion (EI), have been suggested to maximize the therapeutic potential of these antibiotics in critically ill patients. Collectively, the two dosing approaches can also be referred as prolonged infusion (PI).This Thesis aims to better characterize the pharmacokinetics/pharmacodynamics (PK/PD) of betalactam antibiotics to determine whether there is any therapeutic advantage associated with PI dosing (CI and/or EI) as compared to IB dosing. This Thesis comprises of eight chapters. Chapter 1 is an introductory chapter which provides an overview of the published literature on the area of research. The discussion in Chapter 1 presents a theoretical framework behind the Thesis objectives. Chapter 1 concludes with the specific aims of this Thesis.Chapter 2 reports the findings of a prospective PK study which aimed to describe the population PK of doripenem in critically ill patients with sepsis and perform dosing simulations to develop clinically relevant dosing guidelines for these patients. Twelve critically ill participants receiving 500 mg of doripenem 8-hourly as a 1-hr infusion were enrolled. The volume of distribution (Vd) and clearance (CL) of doripenem in this patient cohort were substantially different than those usually described in non-critically patients. As current dosing guidelines were mostly derived from the non-critically ill, findings from this study suggest that the licensed "one-dose-fits-all" dosing for doripenem is unlikely to achieve optimal exposures in critically ill patients. Empirical use of PI dosing should be considered to account for PK and illness severity differences, particularly when less-susceptible pathogens are involved.ii Chapter 3 incorporates a published systematic review which compares the PK/PD data and clinical outcomes between CI and IB dosing to describe any potential merits supporting either of the two dosing approaches for critically ill patients. The findings suggest that beta-lactam CI may not be advantageous for all critically ill patients and may be beneficial in patients with severe infections.Chapter 4 describes the findings of a post hoc analysis on the Defining...

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β-Lactam pharmacokinetics during extracorporeal membrane oxygenation therapy: A case–control study

Cited by 91 publications

References 27 publications

Population Pharmacokinetics and Dose Optimization of Teicoplanin during Venoarterial Extracorporeal Membrane Oxygenation

Population Pharmacokinetics and Dose Optimization of Teicoplanin during Venoarterial Extracorporeal Membrane Oxygenation

Medicating patients during extracorporeal membrane oxygenation: the evidence is building

Optimizing beta-lactam antibiotic dosing in critically ill patients: Prolonged infusion versus intermittent bolus administration

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