Date Published: August 19, 2013
Publisher: Hindawi Publishing Corporation
Author(s): Ashley L. Ross, Jennifer L. Tharp, Gerald R. Hobbs, Richard McKnight, Aaron Cumpston.
Aminoglycoside dosing has been studied in the obese population, typically recommending an adjusted weight utilizing a 40% dosing weight correction factor (IBW + 0.4 × (TBW–IBW)). These studies included limited numbers of morbidly obese patients and were not done in the era of extended interval aminoglycoside dosing. Here, we report a retrospective evaluation of morbidly obese patients receiving gentamicin or tobramycin at our hospital. The objective of this study was to evaluate the accuracy of the commonly recommended adjusted weight for weight-based dosing. There were 31 morbidly obese patients who received gentamicin or tobramycin 5–7 mg/kg every 24 hours using a 40% dosing weight correction factor. Our institution utilizes 16-hour postdose concentrations to monitor extended interval aminoglycosides. Twenty-two of the 31 patients (71%) achieved an appropriate serum drug concentration. Four patients (13%) were found to be supratherapeutic and 5 patients (16%) subtherapeutic. The only variable that correlated with supratherapeutic levels was older age (P = 0.0378). Our study helps to validate the current dosing weight correction factor (40%) in the morbidly obese population. We recommend caution when dosing aminoglycosides in morbidly obese patients who are of older age.
The World Health Organization (WHO) estimated that 500 million people worldwide were obese in 2008 and that number would increase to 700 million by 2015 . In 2011, all 50 states in the United States estimated that 20% or more of their adult population was obese (body mass index ≥ 30 kg/m2); 12 out of the 50 states estimated that more than 30% of their adult population was in this category . Not only the prevalence of obesity is rapidly increasing, but the weight of obese patients continues to rise with five percent of Americans now being considered morbidly obese (body mass index ≥ 40 kg/m2) .
The primary objective of this study was to assess whether previously published DWCF result in appropriate aminoglycoside drug levels in the morbidly obese population utilizing extended interval dosing. Secondary objectives were to determine if there are patient-specific characteristics in the morbidly obese patient that may impact therapeutic level achievement.
Patients receiving extended interval gentamicin or tobramycin for any infectious cause between December 2005 and December 2008 at West Virginia University Healthcare (WVUH) were retrospectively evaluated. Patients were included in the analysis if gentamicin or tobramycin extended interval dosing was used, a 16 hour serum drug concentration was obtained, and patients were 190% or greater than their IBW. IBW was calculated as 2.3x inches over 5 feet in height, plus 45.5 for females and 50 for males. Patients were excluded from the analysis if serum creatinine was greater than 1.5 mg/dL, data was unavailable for estimation of IBW or creatinine clearance (CrCl), they were less than 18 years of age, dialysis patients, obstetric patients, or patients with cystic fibrosis. Patient information was collected from a computerized physician order entry system, an electronic patient database, nursing and physician notes, and billing records. This study was approved by the Institutional Review Board of WVUH.
Statistical analysis was done on all patient variables. The response was categorical. When predictor was categorical, a contingency chi-square test was utilized. Whereas, when a predictor was evaluated, logistic regression analysis was done. A P value of less than 0.05 was interpreted as statistically significant.
Forty patients met the study inclusion and exclusion criteria. Of the 40 patients included in the analysis, 31 patients were dosed within the range of 5–7 mg/kg of ABW using a 40% DWCF. These patients were analyzed to determine appropriateness of serum concentrations achieved as well as to determine if any patient characteristics had an impact on level achievement. The patient demographics on these 31 patients can be found in Table 1. Of the 31 patients dosed with 5–7 mg/kg every 24 hours, 22 patients (71%) had a therapeutic concentration, 4 patients (13%) had a supratherapeutic level, and 5 patients (16%) had a subtherapeutic level.
Our data report morbidly obese patients receiving gentamicin or tobramycin at a dose of 5–7 mg/kg every 24 hours, based on the patient’s ABW and using a 40% DWCF. Serum drug concentrations were found appropriate in 71% of patients. There was also a similar number of patients who were either supratherapeutic or subtherapeutic. This observation is a valuable addition to current knowledge of aminoglycoside use in obesity and expands the available literature, specifically in the morbidly obese patient. It is the first report, to our knowledge, utilizing extended interval dosing in this patient population.
Obese patients have unique pharmacokinetics, which can make drug dosing a difficult task. A 40% DWCF seems to remain accurate in morbidly obese patients, even in the era of extended interval aminoglycoside dosing. We caution practitioners on the dosing of older patients, as they are prone to supratherapeutic levels, even with the estimation of good renal function.