Pharmacokinetics of Vancomycin in Extremely Obese Patients with Suspected or Confirmed <i>Staphylococcus aureus</i>
 Infections

Adane, Eyob D.; Herald, Michael; Koura, Firas

doi:10.1002/phar.1531

Cited by 88 publications

(117 citation statements)

References 42 publications

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“…The boundaries for accuracy used in published reports ranged from <5% to 20%. 22–26 In this study, we aimed for <5% accuracy. Data were analyzed between case and control groups using appropriate tests (ie, paired t test for continuous variables and McNemar test for categorical variables with continuity correction).…”

Section: Methodsmentioning

confidence: 99%

Bayesian Estimation of Vancomycin Pharmacokinetics in Obese Children: Matched Case-Control Study

Lê

Capparelli

Wahid

et al. 2015

Clinical Therapeutics

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Purpose The study objective was to compare different body size descriptors that best estimate vancomycin Vd and clearance (CL). Methods Patients between 3 months and 21 years old who received vancomycin for ≥48 hours from 2003 to 2011 were evaluated in this matched case-control study. Cases had body mass index in the ≥85th percentile; controls were nonobese individuals who were matched by age and baseline serum creatinine (SCr). Using a 1-compartment model with first-order kinetics, Bayesian post hoc individual Vd and CL were estimated. Findings Analysis included 87 matched pairs with 389 vancomycin serum concentrations. Median ages were 10.0 (interquartile range [IQR], 4.8–15.2) years for cases (overweight and obese children) and 10.2 (IQR, 4.5–14.8) years for controls (normal-weight children). Median weights were 44.0 (IQR, 23.4–78.1) kg for cases and 31.3 (IQR, 16.8–47.1) kg for controls. Mean (SD) for the baseline SCr values were also similar between the groups: 0.51 (0.22) (IQR, 0.34–0.67) mg/dL and 0.48 (0.20) (IQR, 0.30–0.60) mg/dL for the cases and controls, respectively. Actual weight and allometric weight (ie, weight0.75) were used in the final model to estimate Vd and CL, respectively. The mean Vd and CL, based on weight, for cases were lower than controls by 0.012 L/kg and 0.014 L/kg/h, respectively. Implications In obese children, actual weight and allometric weight are reasonable, convenient estimations of body fat to use for estimating vancomycin Vd and CL, respectively. However, these pharmacokinetic differences between obese children and those with normal weights are small and may not likely to be clinically relevant in dose variation.

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Section: Methodsmentioning

confidence: 99%

Bayesian Estimation of Vancomycin Pharmacokinetics in Obese Children: Matched Case-Control Study

Lê

Capparelli

Wahid

et al. 2015

Clinical Therapeutics

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“…Two-way analysis of variance was performed (P ϭ 0.02); an asterisk indicates differences at a specific time point according to the Bonferroni post hoc analysis. ing BMI, several studies have suggested that daily vancomycin regimens should be administered according to total body weight (25,26). However, obese patients are at a high risk of insufficient drug concentrations (27), and the measurement of at least two drug concentrations per day, in order to optimize drug regimens in this setting, has been suggested (26).…”

Section: Fig 3 Vancomycin Concentrations At Different Time Points In 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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“…Adane et al 6 performed a prospective pharmacokinetic study in extremely obese patients (BMI $40 kg/m 2 ) who were administered vancomycin for Staphylococcus aureus infections. The vancomycin dosing had to be for at least 3 consecutive days to be included in the investigation.…”

Section: Vancomycinmentioning

confidence: 99%

“…The method involved the determination of population pharmacokinetics for vancomycin using a single compartment intravenous infusion model which was fit to 3 distinct serum concentrations (peak, mid-time point, and a trough concentration) of vancomycin by applying nonlinear mixed-effects modeling. 6 It was found that BW and serum creatinine CL influenced the pharmacokinetic parameter such as volume of distribution (V D ) and CL of vancomycin. By the modeling of all the serum concentration data, the population parameters for V D and CL for vancomycin were 0.51 L/kg, and 6.54 L/h, respectively.…”

Section: Vancomycinmentioning

confidence: 99%

“…The simulations with a probability of $93% predicted that daily doses of vancomycin between 4000 to 5000 mg would be necessary in this population to provide a 24-hour area under the curve (AUC)/minimum inhibitory concentration (MIC) ratio of $400 at a MIC level of 1 mg/mL. 6 The data from this population modeling and simulation analysis suggested that extreme obese patients would need a higher dose of vancomycin and the determination of the initial dose of vancomycin should be made by both total body weight (TBW) and renal function considerations. Although, adjusted body weight (ABW) was also tried for correlations with pharmacokinetic parameters, TBW seemed to be better correlated.…”

Section: Vancomycinmentioning

confidence: 99%

See 1 more Smart Citation

Influence of Morbid Obesity on the Clinical Pharmacokinetics of Various Anti-Infective Drugs: Reappraisal Using Recent Case Studies—Issues, Dosing Implications, and Considerations

Srinivas¹

2018

American Journal of Therapeutics

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Owing to availability of scanty pharmacokinetic data, dosing decisions in morbid obesity is increasingly challenging in the field of anti-infective drugs. However, in recent years data are emerging that describe the pharmacokinetics of anti-infective drugs in morbidly obese subjects. The objectives of the present work were: (1) to collate the recent reports pertaining to the pharmacokinetics in morbidly obese subjects for several anti-infective drugs and provide an overview of the pharmacokinetic data along with the applicable pharmacodynamics and/or clinical outcome; (2) to perform regression analysis on limited dataset for a few drugs to verify the existence of relationships between Cmax/Ctrough versus steady-state volume of distribution (Vss)/clearance to enable data prediction in morbid obesity subjects; (3) to provide a general discussion on issues and dosing implications. The key findings of this review were: (a) drugs such as vancomycin, ethambutol, and fluconazole, where the VSS is substantially greater in morbidly obese patients, need a dosing strategy with the appropriate body mass descriptors; (b) other drugs such as moxifloxacin, linezolid, doripenem, meropenem, voriconazole, oseltamivir, tigecycline, levofloxacin may not ordinarily need dosing adjustments;

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Pharmacokinetics of Vancomycin in Extremely Obese Patients with Suspected or Confirmed Staphylococcus aureus Infections

Cited by 88 publications

References 42 publications

Bayesian Estimation of Vancomycin Pharmacokinetics in Obese Children: Matched Case-Control Study

Bayesian Estimation of Vancomycin Pharmacokinetics in Obese Children: Matched Case-Control Study

New Regimen for Continuous Infusion of Vancomycin in Critically Ill Patients

Influence of Morbid Obesity on the Clinical Pharmacokinetics of Various Anti-Infective Drugs: Reappraisal Using Recent Case Studies—Issues, Dosing Implications, and Considerations

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