How can we ensure effective antibiotic dosing in critically ill patients receiving different types of renal replacement therapy?

Jamal, Janattul Ain; Mueller, Bruce A.; Choi, Gordon; Lipman, Jeffrey; Roberts, Jason A.

doi:10.1016/j.diagmicrobio.2015.01.013

Cited by 73 publications

(85 citation statements)

References 116 publications

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“…For those antibiotics significantly eliminated via renal excretion (i.e. >25-30%), extracorporeal clearance may constitute a substantial proportion of the overall drug clearance, particularly during continuous renal replacement therapy (CRRT) [1,2]. However, it can be extremely challenging to predict drug clearance during RRT because of a complex matrix of factors, including RRT-related factors, pathophysiology, residual renal clearance, and the presence/ alteration of nonrenal clearance pathways.…”

Section: Antibiotic Dosing In Critically Ill Patients Receiving Renalmentioning

confidence: 99%

“…Emerging studies indicate that, in addition to drug accumulation, subtherapeutic antibiotic concentrations may affect the outcome of therapy during renal replacement therapy (RRT) in the critically ill [1,2]. While dosing appropriateness for some drugs could be gauged by objective outcome measures, the lack of a clear 'end-of-needle' effect for antibiotics has made it difficult to ascertain dosing adequacy at the bedside.…”

Section: Antibiotic Dosing In Critically Ill Patients Receiving Renalmentioning

confidence: 99%

“…Specifically, the time that the free-drug concentration remains above the MIC, and the ratio of area under the concentration-time curve or the maximum plasma concentration (C max ) to MIC are the pharmacokinetic/pharmacodynamic (PK/PD) ratios that are best used to describe dosing adequacy for different antibiotics. Current dosing practices may fail to attain target ratios, due to a complex set of factors that alter the PK/PD of antibiotics [2].…”

Section: Antibiotic Dosing In Critically Ill Patients Receiving Renalmentioning

confidence: 99%

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Antibiotic Dosing In Critically Ill Patients Receiving Renal Replacement Therapy

Sime

Roberts

2016

Expert Review of Clinical Pharmacology

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Section: Antibiotic Dosing In Critically Ill Patients Receiving Renalmentioning

confidence: 99%

Section: Antibiotic Dosing In Critically Ill Patients Receiving Renalmentioning

confidence: 99%

Section: Antibiotic Dosing In Critically Ill Patients Receiving Renalmentioning

confidence: 99%

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Antibiotic Dosing In Critically Ill Patients Receiving Renal Replacement Therapy

Sime

Roberts

2016

Expert Review of Clinical Pharmacology

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“…However, very few antibiotic pharmacokinetic studies have been conducted in patients receiving PIRRT, prompting one set of authors to opine that PIRRT is a rational RRT that does not allow for rational drug dosing [8]. Indeed, validated PIRRT dosing recommendations are available for less than 1 % of drugs [8], and there is a growing understanding that inappropriate empiric antibiotic dosing is associated with poor clinical outcomes in critically ill patients [9,10]. More than 70 % of critically ill patients receive antibiotics, and the primary mortality cause in these patients is infection [11].…”

Section: Introductionmentioning

confidence: 99%

In silico trials using Monte Carlo simulation to evaluate ciprofloxacin and levofloxacin dosing in critically ill patients receiving prolonged intermittent renal replacement therapy

et al. 2016

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Background: Prolonged intermittent renal replacement therapy (PIRRT) is a growing option to treat acute kidney injury in critically ill patients, but absent pharmacokinetic data challenge optimal drug dosing. Inappropriate antibiotic dosing can cause widespread bacterial resistance and decreased antibiotic utility. The purpose of this study was to evaluate probability of target attainment (PTA) of various ciprofloxacin and levofloxacin regimens in critically ill patients receiving PIRRT, utilizing Monte Carlo simulation (MCS).

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“…In addition, patients with AKI may be receiving extracorporeal therapies including continuous renal replacement therapy (CRRT) or sustained lowefficiency dialysis (SLED) to remove fluid and wastes from the body, and extracorporeal membrane oxygenation (ECMO) to support impaired cardiac and/or pulmonary systems to maintain appropriate blood gas concentrations. 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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How can we ensure effective antibiotic dosing in critically ill patients receiving different types of renal replacement therapy?

Cited by 73 publications

References 116 publications

Antibiotic Dosing In Critically Ill Patients Receiving Renal Replacement Therapy

Antibiotic Dosing In Critically Ill Patients Receiving Renal Replacement Therapy

In silico trials using Monte Carlo simulation to evaluate ciprofloxacin and levofloxacin dosing in critically ill patients receiving prolonged intermittent renal replacement therapy

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

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