The association of elevated trough serum vancomycin concentrations with obesity

Richardson, Janice; Scheetz, Marc H.; O'Donnell, E. Paul

doi:10.1016/j.jiac.2015.03.007

Cited by 21 publications

(19 citation statements)

References 23 publications

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“…Increasing BMI was associated with a significantly higher proportion of obese patients reaching troughs less than 20 mg/L, even after controlling for dose, S cr , and age . Weight‐normalized Vd (0.3–0.5 vs 0.7 L/kg TBW ) did not scale proportionally in a comparison of morbidly obese patients with obese patients, implying that lower loading doses would be an appropriate adjustment for patient groups with increasing BMIs (loading dose = C max × Vd) .…”

Section: Review Of Specific Antimicrobial Agentsmentioning

confidence: 95%

Comprehensive Guidance for Antibiotic Dosing in Obese Adults

et al. 2017

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Physiologic alterations seen in obesity commonly impact the pharmacokinetics (PK) and pharmacodynamics (PD) of antibiotics and may result in suboptimal dosing in this expanding but understudied population. Much of the published clinical and PK evidence to date consists of small patient populations and are retrospective with, not infrequently, heterogeneous results that in some cases are contradictory. In the last 10 years, additional antimicrobial PK/PD and clinical data encompassing prolonged infusion strategies and examination of critically ill populations have emerged to inform antimicrobial dosing in obesity. In this narrative review, we critically review literature on dosing, PK, and possible dosing strategies in obese adults. We searched PubMed, Scopus, and the Cochrane Library using Medical Subject Headings including anti-infectives, specific antimicrobial names, obese, pharmacokinetics, and others. We reviewed articles, cross-referenced select cited references, and when applicable, referenced drug databases and package inserts to develop dosing recommendations. We provide an overall critical review of the available data regarding PK and dosing issues including dosing recommendations in both critically ill and noncritically ill patients with significant obesity. We developed dosing recommendations for 34 antimicrobials based on 121 articles of the 2336 identified by the search strategy. Although 11 of these do not appear to require dose adjustment, obesity-specific dosing guidance is provided for the remaining 23 antimicrobials. Additional studies are needed to better understand and resolve discrepant published results regarding the PK of antibiotics to establish optimal dosing strategies in obese adults. Alternative dosing strategies, such as extended infusions, should be considered for time-dependent antibiotics (e.g., β-lactams) in obese patients to achieve PD targets reliably. Therapeutic drug monitoring across the spectrum of antimicrobials is of increasing importance in this and other populations to ensure optimized dosing.

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Section: Review Of Specific Antimicrobial Agentsmentioning

confidence: 95%

Comprehensive Guidance for Antibiotic Dosing in Obese Adults

et al. 2017

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“…Almost half of our patients (48%) had subtherapeutic trough concentrations. Data are consistent with most published reports on vancomycin dosing in obese patients and ability to achieve “target concentrations.” In a small study that included 37 obese patients, 57% had trough levels < 15 mg/L . In a multicenter study, 99% (252/254 patients) of overweight and obese patients did not receive the recommended vancomycin dose (15 mg/kg/dose) .…”

Section: Discussionmentioning

confidence: 99%

Vancomycin Dosing Considerations in a Real‐World Cohort of Obese and Extremely Obese Patients

et al. 2015

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Study Objective To compare the effects of empiric vancomycin dosing regimens on attainment of optimal target trough concentrations in obese (body mass index [BMI] 30–40 kg/m2) and extremely obese (BMI ≥ 40 kg/m2) patients. Design Retrospective cohort study. Data Source National Veterans Affairs standardized databases. Patients A total of 263 obese and 71 extremely obese (actual body weight range 72–244 kg in both groups) inpatients from all Veterans Affairs facilities nationally who had suspected methicillin‐resistant Staphylococcus aureus pneumonia and were treated with vancomycin between 2002 and 2012. Measurements and Main Results Patients with steady‐state trough concentrations (measured ≤ 2 hours before the next vancomycin dose) and no evidence of acute kidney injury before vancomycin initiation were included. Logistic regression models were used to measure the effect of various vancomycin dosing regimens on attainment of optimal target trough concentrations (15–20 mg/L). The mean total daily vancomycin dose was lower in obese versus extremely obese patients (2005 ± 736 vs 2306 ± 934 mg, p<0.05). The mean weight‐based daily dose was higher in obese patients (20 ± 7 vs 17 ± 7 mg/kg/day, p<0.05). In each group, ~ 20% of patients achieved optimal target trough concentrations. In obese patients, the standard dose of ~ 30 mg/kg/day was appropriate for target trough concentration attainment (odds ratio 5.15, 95% confidence interval 1.69–15.64). In extremely obese patients, a lower dosage of 20 to 25 mg/kg/day was appropriate for target trough concentration attainment (odds ratio 6.07, 95% confidence interval 1.01–36.51). Conclusion In this real‐world study, we offer additional consideration of vancomycin dosing in obese and extremely obese patients. Extremely obese patients may require a lower weight‐based daily dose than obese patients to reach target vancomycin trough concentrations.

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“…There was no significant relationship between obesity and a higher risk of nephrotoxicity [Davies et al 2015;Matson et al 2015]. However, a different outcome was obtained in another study: there was fivefold greater likelihood of attaining a serum vancomycin greater than 20 mg/l in patients with exogenous obesity [Richardson et al 2015].…”

Section: Vancomycin Exposure: Synergism With Nephrotoxic Agentsmentioning

confidence: 90%

Review of vancomycin-induced renal toxicity: an update

Bamgbola

2016

Therapeutic Advances in Endocrinology

180

145

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Abstract:In recent times the use of larger doses of vancomycin aimed at curbing the increasing incidence of resistant strains of Staphylococcus aureus has led to a wider report of acute kidney injury (AKI). Apart from biological plausibility, causality is implied by the predictive association of AKI with larger doses, longer duration, and graded plasma concentrations of vancomycin. AKI is more likely to occur with the concurrent use of nephrotoxic agents, and in critically ill patients who are susceptible to poor renal perfusion. Although most vancomycin-induced AKI cases are mild and therefore reversible, their occurrence may be associated with greater incidence of end-stage kidney disease and higher mortality rate. The strategy for its prevention includes adequate renal perfusion and therapeutic drug monitoring in high-risk individuals. In the near future, there is feasibility of renoprotective use of antioxidative substances in the delivery of vancomycin.

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The association of elevated trough serum vancomycin concentrations with obesity

Cited by 21 publications

References 23 publications

Comprehensive Guidance for Antibiotic Dosing in Obese Adults

Comprehensive Guidance for Antibiotic Dosing in Obese Adults

Vancomycin Dosing Considerations in a Real‐World Cohort of Obese and Extremely Obese Patients

Review of vancomycin-induced renal toxicity: an update

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