A new regimen for continuous infusion of vancomycin during continuous renal replacement therapy

Beumier, Marjorie; Roberts, Jason A.; Kabtouri, Hakim; Hites, Maya; Cotton, Frédéric; Wolff, Fleur; Lipman, Jeffrey; Jacobs, Frédérique; Vincent, Jean‐Louis; Taccone, Fabio Silvio

doi:10.1093/jac/dkt261

Cited by 52 publications

(71 citation statements)

References 35 publications

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“…CoI seems to be more successful under these conditions to achieve the PK/PD targets. The weight-based CoI proposed by Beumier et al (52) achieved an AUC/MIC ratio of Ͼ400 in all patients with a MIC of Յ1 mg/liter and for 72% of patients when the MIC was 1.5 mg/liter. In contrast, the largest vancomycin population PK analysis conducted in patients undergoing CRRT and receiving CoI of vancomycin was not able to quantify the effect of CRRT on vancomycin pharmacokinetics (54).…”

Section: Renal Replacement Therapiesmentioning

confidence: 97%

See 1 more Smart Citation

Optimizing the Clinical Use of Vancomycin

Álvarez

López-Cortés

Molina

et al. 2016

Antimicrob Agents Chemother

192

124

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Pharmacists published specific guidelines about vancomycin dosage and monitoring. However, these guidelines have not been updated in the past 6 years. This review analyzes the new available information about vancomycin published in recent years regarding pharmacokinetics and pharmacodynamics, serum concentration monitoring, and optimal vancomycin dosing in special situations (obese people, burn patients, renal replacement therapy, among others). Vancomycin efficacy is linked to a correct dosage which should aim to reach an area under the curve (AUC)/MIC ratio of >400; serum trough levels of 15 to 20 mg/liter are considered a surrogate marker of an AUC/MIC ratio of >400 for a MIC of <1 mg/liter. For Staphylococcus aureus strains presenting with a MIC >1 mg/liter, an alternative agent should be considered. Vancomycin doses must be adjusted according to body weight and the plasma trough levels of the drug. Nephrotoxicity has been associated with target vancomycin trough levels above 15 mg/liter. Continuous infusion is an option, especially for patients at high risk of renal impairment or unstable vancomycin clearance. In such cases, vancomycin plasma steady-state level and creatinine monitoring are strongly indicated. Vancomycin has traditionally been used as a first-line agent for treating methicillin-resistant Staphylococcus aureus (MRSA) and other Gram-positive beta-lactam-resistant bacteria (1), which are frequent etiologies of severe health-related infections (2, 3).Although the effectiveness of vancomycin is supported by more than 5 decades of use and multiple studies, the clinical and microbiological scenario in which it is used is always changing. Attaining an appropriate dosage of vancomycin for S. aureus infections might be difficult due to the clinical impact of the creep in the MIC of vancomycin and heteroresistance among MRSA strains, or due to complex pharmacokinetic and pharmacodynamic (PK/PD) situations. In this context, the American Society of Health-System Pharmacists (ASHP), the Infectious Diseases Society of America (IDSA), and the Society of Infectious Diseases Pharmacists (SIDP) introduced a practice guideline in 2009 (4), marking a milestone in vancomycin therapy. However, several questions, such as the optimal dosing in some special clinical situations (e.g., with renal replacement therapies or in burn patients or obese patients), the role of continuous infusion, or the renal toxicity when the suggested vancomycin serum levels are achieved, remain unanswered. The present review mainly focuses on these issues. VANCOMYCIN PHARMACODYNAMICS AND ITS IMPLICATIONS FOR DRUG MONITORINGThe killing effect of vancomycin is characterized by a slow mode of action and is further hampered by a large bacterial inoculum, a stationary growth phase, and anaerobic conditions (5, 6). Although several pharmacodynamic parameters have been proposed to determine vancomycin activity, data from experimental and clinical studies have selected the area under the curve (AUC)/ MIC ratio as the best parameter to predict the...

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Section: Renal Replacement Therapiesmentioning

confidence: 97%

“…Different dosages, either for continuous or intermittent vancomycin therapy, have been proposed in recent PK observational studies (51)(52)(53)(54)(55)(56) to understand the best dosages in patients receiving CRRT. CoI seems to be more successful under these conditions to achieve the PK/PD targets.…”

Section: Renal Replacement Therapiesmentioning

confidence: 99%

Optimizing the Clinical Use of Vancomycin

Álvarez

López-Cortés

Molina

et al. 2016

Antimicrob Agents Chemother

192

124

View full text Add to dashboard Cite

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“…Numerous pharmacokinetic studies of vancomycin in critically ill patients receiving varying types of RRT have been published (Beumier et al, 2013;Chaijamorn et al, 2011;DelDot et al, 2004;Kielstein et al, 2006;Macias et al, 1991;Petejova et al, 2012bPetejova et al, , 2012c. The vancomycin Sc is reported to be between 0.7 and 0.9 during CVVH/ CVVHDF for effluent flow rates between 20 and 50 mL/min (Chaijamorn et al, 2011;DelDot et al, 2004;Petejova et al, 2012b).…”

Section: Glycopeptidesmentioning

confidence: 99%

“…Indeed such dosing has been validated in one study (Beumier et al, 2013), to increase the achievement of the PK/PD target, AUC/MIC ratio ≥400 (Rybak et al, 2009). Therapeutic drug monitoring to guide dosing is essential, as returning native renal function can increase vancomycin clearance in the presence of CRRT (Macias et al, 1991).…”

Section: Glycopeptidesmentioning

confidence: 99%

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

Jamal

Mueller

Choi

et al. 2015

Diagnostic Microbiology and Infectious Disease

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“…For example, Beumier and colleagues developed a population pharmacokinetics model for vancomycin administered as a continuous infusion in critically ill patients with sepsis and septic shock, and found that inclusion of CRRT intensity as a covariate on CL significantly improved the model [52]. Similarly, a study by Bilgrami and colleagues specifically targeted patients with high-intensity CRRT (>4 l/hour) receiving meropenem and found that total drug CL was higher compared with previous studies with lower intensity CRRT, intensity being the main parameter that accounted for the differences in meropenem CL ( R 2 = 0.89) [15].…”

Section: Main Limitations Of Available Pharmacokinetic Studiesmentioning

confidence: 99%

Beta-lactam dosing in critically ill patients with septic shock and continuous renal replacement therapy

et al. 2014

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Although early and appropriate antibiotic therapy remains the most important intervention for successful treatment of septic shock, data guiding optimization of beta-lactam prescription in critically ill patients prescribed with continuous renal replacement therapy (CRRT) are still limited. Being small hydrophilic molecules, beta-lactams are likely to be cleared by CRRT to a significant extent. As a result, additional variability may be introduced to the per se variable antibiotic concentrations in critically ill patients. This article aims to describe the current clinical scenario for beta-lactam dosing in critically ill patients with septic shock and CRRT, to highlight the sources of variability among the different studies that reduce extrapolation to clinical practice, and to identify the opportunities for future research and improvement in this field. Three frequently prescribed beta-lactams (meropenem, piperacillin and ceftriaxone) were chosen for review. Our findings showed that present dosing recommendations are based on studies with drawbacks limiting their applicability in the clinical setting. In general, current antibiotic dosing regimens for CRRT follow a one-size-fits-all fashion despite emerging clinical data suggesting that drug clearance is partially dependent on CRRT modality and intensity. Moreover, some studies pool data from heterogeneous populations with CRRT that may exhibit different pharmacokinetics (for example, admission diagnoses different to septic shock, such as trauma), which also limit their extrapolation to critically ill patients with septic shock. Finally, there is still no consensus regarding the %T>MIC (percentage of dosing interval when concentration of the antibiotic is above the minimum inhibitory concentration of the pathogen) value that should be chosen as the pharmacodynamic target for antibiotic therapy in patients with septic shock and CRRT. For empirically optimized dosing, during the first day a loading dose is required to compensate the increased volume of distribution, regardless of impaired organ function. An additional loading dose may be required when CRRT is initiated due to steady-state equilibrium breakage driven by clearance variation. From day 2, dosing must be adjusted to CRRT settings and residual renal function. Therapeutic drug monitoring of beta-lactams may be regarded as a useful tool to daily individualize dosing and to ensure optimal antibiotic exposure.

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A new regimen for continuous infusion of vancomycin during continuous renal replacement therapy

Abstract: This new vancomycin regimen allowed the rapid achievement of target drug concentrations in the majority of patients. CRRT intensity had an influence on vancomycin clearance.

Cited by 52 publications

References 35 publications

Optimizing the Clinical Use of Vancomycin

Optimizing the Clinical Use of Vancomycin

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

Beta-lactam dosing in critically ill patients with septic shock and continuous renal replacement therapy

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