Vancomycin dosing in obese and morbidly obese patients
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Vancomycin dosing and individualization of therapy in obese patients continues to be a challenge faced by clinicians throughout the United States and around the world. Most vancomycin dosing guidelines in use today recommend dose adjustments based on total-body weight which may not be ideal for obese and super obese patients.1
Pharmacokinetics of vancomycin in obese patients
Vancomycin has been in clinical use since the 1950’s. Despite its wide-spread use and success in treating challenging infections such as methicillin-resistant Staphylococcus aureus, its use is still perhaps described as challenging for clinicians, especially in patient cohorts such as the obese. A recent meta-analysis (van Hal et al. 2013) demonstrates this, finding vancomycin-associated nephrotoxicity rates of up to 43% at some sites, with a relative risk of 2.45 (95% CI 1.69-3.55).2 In obese patients, however, this risk would reasonably be expected to be even higher – obesity is well known to correlate with impaired renal function.
Vancomycin is a hydrophilic drug, however, in obesity both adipose tissue and lean muscle mass are increased. While pharmacokinetic studies have shown that the volume of distribution of vancomycin increases with increased actual body weight, it does not appear to increase proportionally, and in fact is challenging to reliably predict – models (and model-developed dosing nomograms) are unable to explain more than 50% of inter-individual variation in the obese without the use of individualized, precision dosing.
Calculating individual, precise vancomycin doses for obese patients
The obese, one-compartment vancomycin adult model implemented in DoseMeRx is derived from a prospective pharmacokinetic study with a cohort of 31 patients (Adane et al. 2015).3 All patients in the study were morbidly obese with a body mass index ≥40 kg/m2 with median weight of 147.9 kg. The authors found both altered clearance and volume of distribution in obese patients when compared to non-obese models. In particular, the relationship between creatinine clearance and vancomycin clearance was found to be best described by normalizing by obesity (BSA).
How do you dose vancomycin in obese patients?
Dosing to trough is the primary dosing target in this patient population as the model was primarily built by fitting trough targets providing limited information to establish the predictive performance of an area-under the curve (AUC) fit.
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