Vancomycin Dosing in Critically Ill Patients: Robust Methods for Improved Continuous-Infusion Regimens

Roberts, Jason A.; Taccone, Fabio Silvio; Udy, Andrew; Vincent, Jean‐Louis; Jacobs, Frédérique; Lipman, Jeffrey

doi:10.1128/aac.01708-10

Cited by 199 publications

(205 citation statements)

References 34 publications

(32 reference statements)

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“…The largest PK study on CoI of vancomycin showed that dosages need to be individualized according to the actual body weight (ABW) and creatinine clearance (CrCl) of the patient (44). To achieve a steady-state concentration of Ն20 mg/liter, these authors propose a minimum loading dose of 35 mg/kg, followed by…”

Section: Intermittent Versus Continuous Infusion Therapymentioning

confidence: 99%

Optimizing the Clinical Use of Vancomycin

Álvarez

López-Cortés

Molina

et al. 2016

Antimicrob Agents Chemother

190

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: Intermittent Versus Continuous Infusion Therapymentioning

confidence: 99%

Optimizing the Clinical Use of Vancomycin

Álvarez

López-Cortés

Molina

et al. 2016

Antimicrob Agents Chemother

190

124

View full text Add to dashboard Cite

show abstract

“…As such, Roberts et al (8), using a population PK analysis, suggested that a vancomycin loading dose of 35 mg/kg, followed by daily doses adjusted to creatinine clearance (CrCL, ranging from 7 to 45 mg/kg/day), would rapidly achieve adequate drug concentrations in critically ill patients. Nevertheless, this approach has not been prospectively validated yet.…”

mentioning

confidence: 99%

New Regimen for Continuous Infusion of Vancomycin in Critically Ill Patients

Cristallini

Hites

Kabtouri

et al. 2016

Antimicrob Agents Chemother

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Vancomycin remains a primary treatment for infections caused by Gram-positive bacteria resistant to ␤-lactam antibiotics, including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), and ampicillin-resistant enterococci (1). Despite extensive clinical use of vancomycin over recent years, the optimal dosing strategy for rapid achievement of therapeutic concentrations still remains a challenge for physicians. This is of particular interest for patients with septic shock, who require adequate antibiotic therapy, especially in terms of drug concentrations, from the early phase of treatment (2, 3). To rapidly achieve optimal vancomycin concentrations in such patients, a loading dose followed by a continuous drug infusion (CI) has been proposed (4).Although CI of vancomycin is increasingly used, especially in the intensive care unit (ICU), there is still a controversy as to whether this mode of administration provides better results than standard intermittent drug administration (II). Several studies have shown no differences in clinical efficacy or mortality between the two therapeutic strategies in infections with Gram-positive bacteria (4-6). However, Wysocki et al. (5) demonstrated that CI allowed faster achievement of target concentrations, presented less variability in drug concentrations, and resulted in reduced costs of therapy. Furthermore, a recent meta-analysis showed that CI was associated with a significantly lower risk of drug-related nephrotoxicity than II, despite the use of similar daily doses (6).Nevertheless, because of significant changes in vancomycin pharmacokinetics (PK) during critical illness, such as increased volume of distribution (V) and augmented clearance, the standard CI regimen (e.g., a loading dose of 15 mg/kg of body weight, followed by 30 mg/kg over 24 h for patients with normal renal function) (5) has been associated with inadequate drug concentrations in a high proportion of septic patients in the first 2 days of therapy (7). As such, Roberts et al. (8), using a population PK analysis, suggested that a vancomycin loading dose of 35 mg/kg, followed by daily doses adjusted to creatinine clearance (CrCL, ranging from 7 to 45 mg/kg/day), would rapidly achieve adequate drug concentrations in critically ill patients. Nevertheless, this approach has not been prospectively validated yet.Another important issue concerning vancomycin is that clinical efficacy is best predicted when the ratio between the area under the curve of drug concentrations over 24 h (AUC 0 -24 ) and the MIC for the pathogen isolated (AUC 0 -24 /MIC) exceeds 400 (9-12). To ensure optimal AUC 0 -24 /MIC ratios, several studies have proposed target serum drug concentrations between 15 and 30 mg/liter during CI of vancomycin (5, 13-15). Nevertheless, no study has evaluated the correlation between vancomycin concentrations and the achievement of an AUC 0 -24 /MIC ratio of Ն400 in critically ill patients, in particular during the first day of therapy.The aim of thi...

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“…Although there is a paucity of pediatric literature related to the pharmacodynamics and kinetics of antibiotics in severe sepsis, there is a body of evidence in the adult literature showing that antibiotic levels of drugs such as ertapenem [58,59], beta-lactams and vancomycin may vary considerably in severe sepsis depending on the specific context [59][60][61][62][63], including albumin and creatinine levels. Drugs such as aminoglycosides may accumulate in patients with severe sepsis, but there may also be augmented excretion of antibiotics such as beta-lactams with resultant poor therapeutic levels [64].…”

Section: Antibioticsmentioning

confidence: 99%

What’s New in the Recognition and Management of Septic Shock in Children: Dos and Don'ts

Argent

2013

Curr Pediatr Rep

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While there has been a reduction in the number of children dying of septic shock in the richer countries of the world, septic shock remains an important cause of both mortality and morbidity for children across the world. Major reduction in the incidence of septic shock will depend on the implementation of public health measures, including immunization. Improvements in outcome of pediatric septic shock have been closely linked to early recognition (although this may be challenging in many situations); early antibiotic administration; early and appropriate fluid administration and subsequent escalation of critical care. A particular challenge has been the development and implementation of systems to ensure that these elements of management are reliably and efficiently implemented in children (even in well-resourced countries). Recent studies have highlighted the complexity of caring for patients with acute severe sepsis and septic shock in countries with fewer resources, and there is an urgent need for further studies to elucidate the implications of these studies for the management of children with septic shock, particularly in settings where additional critical care support such as inotropic or ventilator support may not be readily available.

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Vancomycin Dosing in Critically Ill Patients: Robust Methods for Improved Continuous-Infusion Regimens

Cited by 199 publications

References 34 publications

Optimizing the Clinical Use of Vancomycin

Optimizing the Clinical Use of Vancomycin

New Regimen for Continuous Infusion of Vancomycin in Critically Ill Patients

What’s New in the Recognition and Management of Septic Shock in Children: Dos and Don'ts

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