Altered vancomycin pharmacokinetics in obese and morbidly obese patients: what we have learned over the past 30 years

Grace, E. E.

doi:10.1093/jac/dks066

Cited by 88 publications

(73 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Besides, it is associated with an increase in certain circulating proteins, which results in altered free serum vancomycin concentrations. Increased blood flow secondary to increased cardiac output and blood volume also occurs, resulting in increased vancomycin clearance (61). Achieving adequate vancomycin serum levels and similar efficacy without a high risk of toxicity is a current challenge (62).…”

Section: Vancomycin and Obesitymentioning

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

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...

show abstract

Section: Vancomycin and Obesitymentioning

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

show abstract

“…In the previous evaluation of this technique (6) there was limited representation of obese patients (6,(10)(11)(12). Given potential differences in PK profiles between obese and nonobese (13) and the increasing prevalence of obesity in the United States, (14), the limited PK Bayesian AUC monitoring approach needs to be examined in patients with obesity before widespread adoption. Cognizant of this critical gap in the literature, this pilot study was conducted to determine whether the vancomycin AUC can be accurately predicted using Bayesian estimation techniques with limited PK samples in obese patients.…”

mentioning

confidence: 99%

Pilot Study of a Bayesian Approach To Estimate Vancomycin Exposure in Obese Patients with Limited Pharmacokinetic Sampling

Carreno

Lomaestro

Tietjan

et al. 2017

Antimicrob Agents Chemother

View full text Add to dashboard Cite

This study evaluated the predictive performance of a Bayesian PK estimation method (ADAPT V) to estimate the 24-h vancomycin area under the curve (AUC) with limited pharmacokinetic (PK) sampling in adult obese patients receiving vancomycin for suspected or confirmed Gram-positive infections. This was an Albany Medical Center Institutional Review Board-approved prospective evaluation of 12 patients. Patients had a median (95% confidence interval) age of 61 years (39 to 71 years), a median creatinine clearance of 86 ml/min (75 to 120 ml/min), and a median body mass index of 45 kg/m 2 (40 to 52 kg/m 2 ). For each patient, five PK concentrations were measured, and four different vancomycin population PK models were used as Bayesian priors to estimate the vancomycin AUC (AUC FULL ). Using each PK model as a prior, data-depleted PK subsets were used to estimate the 24-h AUC (i.e., peak and trough data [AUC PT ], midpoint and trough data [AUC MT ], and trough-only data [AUC T ]). The 24-h AUC derived from the full data set (AUC FULL ) was compared to the AUC derived from data-depleted subsets (AUC PT , AUC MT , and AUC T ) for each model. For the four sets of analyses, AUC FULL estimates ranged from 437 to 489 mg·h/liter. The AUC PT provided the best approximation of the AUC FULL ; AUC MT and AUC T tended to overestimate AUC FULL . Further prospective studies are needed to evaluate the impact of AUC monitoring in clinical practice, but the findings from this study suggest that the vancomycin AUC can be estimated with good precision and accuracy with limited PK sampling using Bayesian PK estimation software.

show abstract

“…This phenomenon is magnified for lipophilic medications, which tend to more readily distribute than hydrophilic drugs. Previous work has identified larger V d in obese patients for most classes of antimicrobial agents, including penicillins, cephalosporins, carbapenems, aminoglycosides, vancomycin, and others [16][17][18][19][20][21][22][23][24][25]. The extent to which a medication is protein-bound also affects V d , and obesity has been shown to alter lipoproteins and alpha1-acid glycoprotein [2].…”

Section: Discussionmentioning

confidence: 99%

Obesity Is Not Associated with Antimicrobial Treatment Failure for Intra-Abdominal Infection

Dietch

Duane

Cook

et al. 2016

Surgical Infections

View full text Add to dashboard Cite

Background: Obesity and commonly associated comorbidities are known risk factors for the development of infections. However, the intensity and duration of antimicrobial treatment are rarely conditioned on body mass index (BMI). In particular, the influence of obesity on failure of antimicrobial treatment for intra-abdominal infection (IAI) remains unknown. We hypothesized that obesity is associated with recurrent infectious complications in patients treated for IAI. Methods: Five hundred eighteen patients randomized to treatment in the Surgical Infection Society Study to Optimize Peritoneal Infection Therapy (STOP-IT) trial were evaluated. Patients were stratified by obese (BMI ‡30) versus non-obese (BMI ‡30) status. Descriptive comparisons were performed using Chi-square test, Fisher exact test, or Wilcoxon rank-sum tests as appropriate. Multivariable logistic regression using a priori selected variables was performed to assess the independent association between obesity and treatment failure in patients with IAI. Results: Overall, 198 (38.3%) of patients were obese (BMI ‡30) versus 319 (61.7%) who were non-obese. Mean antibiotic d and total hospital d were similar between both groups. Unadjusted outcomes of surgical site infection (9.1% vs. 6.9%, p = 0.36), recurrent intra-abdominal infection (16.2% vs. 13.8, p = 0.46), death (1.0% vs. 0.9%, p = 1.0), and a composite of all complications (25.3% vs. 19.8%, p = 0.14) were also similar between both groups. After controlling for appropriate demographics, comorbidities, severity of illness, treatment group, and duration of antimicrobial therapy, obesity was not independently associated with treatment failure (c-statistic: 0.64). Conclusions: Obesity is not associated with antimicrobial treatment failure among patients with IAI. These results suggest that obesity may not independently influence the need for longer duration of antimicrobial therapy in treatment of IAI versus non-obese patients.

show abstract

Altered vancomycin pharmacokinetics in obese and morbidly obese patients: what we have learned over the past 30 years

Cited by 88 publications

References 30 publications

Optimizing the Clinical Use of Vancomycin

Optimizing the Clinical Use of Vancomycin

Pilot Study of a Bayesian Approach To Estimate Vancomycin Exposure in Obese Patients with Limited Pharmacokinetic Sampling

Obesity Is Not Associated with Antimicrobial Treatment Failure for Intra-Abdominal Infection

Contact Info

Product

Resources

About