An Evaluation of Systemic Vancomycin Dosing in Obese Patients.
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ABSTRACT:
SUBMITTER: Kubiak DW
PROVIDER: S-EPMC4691676 | biostudies-literature | 2015 Dec
REPOSITORIES: biostudies-literature
Publications
An Evaluation of Systemic Vancomycin Dosing in Obese Patients.
Kubiak David W DW Alquwaizani Mohammed M Sansonetti David D Barra Megan E ME Calderwood Michael S MS
Open forum infectious diseases 20151113 4
We retrospectively identified 67 patients with severe or morbid obesity (body mass index ≥35 kg/m(2)) who had received intravenous vancomycin at our institution. We observed that an initial dose of 45 to 65 mg/kg vancomycin per day based upon ideal body weight rather than actual body weight was more predictive of initial trough concentrations between 15 and 20 mcg/mL. ...[more]
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Project description:Background and objectiveThe latest vancomycin guideline recommends area under the curve (AUC)-targeted dosing and monitoring for efficacy and safety. However, guidelines for AUC-targeted starting dosing in patients with obesity and/or renal insufficiency are currently lacking. This study quantifies the pharmacokinetics (PK) of vancomycin in this population and provides AUC-targeted dosing recommendations.MethodsVancomycin concentrations (n = 1188) from therapeutic drug monitoring of 210 overweight and obese patients with varying degrees of renal (dys)function from the ward (74.8%) and intensive care unit (ICU, 25.2%) were pooled with published rich concentration-time data (n = 207) from 20 (morbidly) obese subjects undergoing bariatric surgery. A population model was developed using NONMEM 7.4. Stochastic simulations were performed to design dosing guidelines targeting an AUC24 between 400-600 mg·h/L.ResultsVancomycin clearance (CL) was found to increase linearly with total bodyweight and with renal function (CKD-EPI) in a power relation. Additionally, CL proved 15.5% lower in ICU patients. Our model shows that, to reach the target AUC between 400 and 600 mg·h/L in the first 48 h, two loading doses are required for both continuous infusion and intermittent dosing regimens. Maintenance doses were found to require adjustment for total bodyweight, renal function, and ICU admission status. With this guideline, the median AUC24 is well within the target from the start of the treatment onwards.ConclusionsTo achieve safe and effective vancomycin exposure for maintenance doses in overweight and obese patients, renal function, total bodyweight, and ICU admission status should be taken into account.Trial registrationThe AMIGO trial was registered in the Dutch Trial Registry [NTR6058].
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Project description:The purpose of this study was to investigate the population pharmacokinetics of vancomycin in patients undergoing open heart surgery. In this observational pharmacokinetic study, multiple blood samples were drawn over a 48-h period of intravenous vancomycin in patients who were undergoing open heart surgery. Blood samples were analyzed using an Architect i4000SR immunoassay analyzer. Population pharmacokinetic models were developed using Monolix 4.4 software. Pharmacokinetic-pharmacodynamic (PK-PD) simulations were performed to explore the ability of different dosage regimens to achieve the pharmacodynamic targets. A total of 168 blood samples were analyzed from 28 patients. The pharmacokinetics of vancomycin are best described by a two-compartment model with between-subject variability in clearance (CL), the volume of distribution of the central compartment (V1), and volume of distribution of the peripheral compartment (V2). The CL and the V1 of vancomycin were related to creatinine CL (CLCR), body weight, and albumin concentration. Dosing simulations showed that standard dosing regimens of 1 and 1.5 g failed to achieve the PK-PD target of AUC0-24/MIC > 400 for an MIC of 1 mg/liter, while high weight-based dosing regimens were able to achieve the PK-PD target. In summary, the administration of standard doses of 1 and 1.5 g of vancomycin two times daily provided inadequate antibiotic prophylaxis in patients undergoing open heart surgery. The same findings were obtained when 15- and 20-mg/kg doses of vancomycin were administered. Achieving the PK-PD target required higher doses (25 and 30 mg/kg) of vancomycin.
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