An AUC Target Simulation for Vancomycin in Patients With Class III Obesity.

OBJECTIVE: The objective of this simulation is to compare 24-hour vancomycin (Vanc24) dosage requirements between a target area under the curve (AUC) versus a target trough approach in patients with class III obesity. METHODS: Adult patients were included if they received vancomycin in accordance with the University of Vermont Medical Center's class III obesity dosage protocol from June 2016 through December 2018. Patient-specific pharmacokinetic parameters were calculated for each patient using the Sawchuck-Zaske method. For this simulation, Vanc24 dosages were calculated to achieve an AUC of 400 mg/L h and a trough concentration of 15 mg/L. RESULTS: Sixty-three patients had Vanc24 dosage requirements calculated. The median age was 59 years (interquartile range [IQR]: 51.5-68), body mass index (BMI): 45.7 kg/m2 (IQR: 42.4-51.5), and 50.7% were male. The mean Vanc24 dosage requirements were 3995 mg (standard deviation [SD] ±1673) in the target trough approach versus 2783 mg (SD ±1149) in the target AUC approach (P < .0001). CONCLUSION: A target AUC approach required less vancomycin over a 24-hour time period relative to a target trough approach. Vancomycin therapeutic drug monitoring that explicitly targets AUC may reduce vancomycin exposure and potentially decrease the risk of nephrotoxicity in patients with class III obesity.

Proton Pump Inhibitor-Induced Galactorrhea in a Kidney Transplant Recipient: A Friend or Foe?

Over the last decades, proton pump inhibitors (PPIs) have been widely used as the mainstay for treatment and prevention of gastrointestinal side effects, gastroesophageal reflux, and peptic ulcer disease. However, their safety profile has come into question recently after reports relating them to several side effects as well as kidney disease. Omeprazole, one of the mainly used PPIs, is almost entirely metabolized by the liver but the resulting metabolites are renally excreted. These metabolites may inhibit cytochrome P450 2C19 (CYP2C19) and cytochrome P450 3A4 (CYP3A4) reversibly, but as recent evidence suggests, they may also be involved in causing kidney disease. In the setting of renal dysfunction, these metabolites will not be excreted from the body and will accumulate further causing kidney damage and inhibiting CYP enzymes to a greater extent. Abnormally high serum prolactin levels leading to galactorrhea may be the result of such an accumulation. To our knowledge, there have been only three previously reported cases of PPI-induced galactorrhea in the literature but none in a kidney transplant recipient. In patients with established kidney disease and reduced glomerular filtration rate like kidney transplant recipients, the use of PPIs should be thoroughly assessed. Reduced clearance of their metabolites may lead to progression of the kidney disease and lead to more unwanted side effects. We present a case of a female kidney transplant recipient with worsening allograft function who presented with sudden galactorrhea and hyperprolactinemia while on a high-dose omeprazole for gastroesophageal reflux disease.

Identification of Risk Factors for Initial Elevated Vancomyin Trough Concentrations.

Background: Recent literature suggests that elevated vancomycin trough concentrations (>20 µg/mL) may be associated with an increased risk of nephrotoxicity and lead to an increase in mortality and hospital length of stay. Objective: The purpose of this study was to identify variables that may be predictive of elevated initial vancomycin trough concentrations. Methods: Retrospective case-control study of all adult patients who had an initial vancomycin trough concentration measured between January 1, 2013, and December 31, 2014. Case patients had an initial trough concentration >20 µg/mL, while control patients had an initial trough concentration of ≤20 µg/mL. Patients were excluded from the study if they were in the intensive care unit, had unstable renal function, or if they had cystic fibrosis, solid organ transplant, or bone marrow transplant. Results: Of the 512 vancomycin trough concentrations reviewed, 54 patients met the case definition, while 140 patients were randomly selected as controls. In a multivariate model, baseline serum creatinine, body mass index, heart failure, and malignancy were all independently predictive of an initial vancomycin concentration >20 µg/mL. Conclusions: Reduced baseline renal function coupled with increasing body mass index is associated with an increased risk of an elevated initial vancomycin trough concentration. This risk is further enhanced by the presence of heart failure and/or malignancy. When these risk factors are present, it may be prudent to consider implementation of individualized dosing to achieve initial target concentrations.