1102. Evaluation of Vancomycin Accumulation in Patients with Obesity

Abstract Background Current vancomycin guidelines recommend using actual body weight for dosing. However, in patients with obesity, this may result in lower initial vancomycin concentrations that can accumulate with continued doses due to differences in volume of distribution. The objective of this study is to evaluate the incidence of vancomycin accumulation in patients with obesity and identify potential factors associated with accumulation. Methods This is a single-center, retrospective, observational study at a tertiary academic medical center. Adult patients with a BMI ≥ 30 kg/m2 and with ≥ 2 vancomycin serum trough concentrations within the same encounter in 2019 were screened. Patients were excluded if they were pregnant, had unstable renal function or severe renal impairment, received < 3 doses before a concentration was drawn, or had inconsistent dosing prior to a concentration draw. Linear kinetics were used to correct for differences in timing of concentration or dose changes. The major endpoint was the incidence of vancomycin accumulation, defined as a 20% increase in trough concentration between the first and any subsequent trough concentrations within the first 10 days of therapy. Minor endpoints included the percentage of supratherapeutic concentrations and the incidence of acute kidney injury (AKI). Descriptive statistics were used to evaluate endpoints and multivariable logistic regression was used to evaluate factors associated with accumulation. Results We screened 543 patients, and 162 were included in our analysis. The median age was 56.5 years (interquartile range [IQR] 43 - 65.3), and 62.3% were male. The median weight was 112.7 kg (IQR 99.8 - 122.6) and the median BMI was 36.8 kg/m2 (IQR 33.1 - 41). The median total daily vancomycin dose at initiation was 28.7 mg/kg/day (IQR 25.4 - 31.2). Vancomycin accumulation occurred in 99 patients (61.1%) within the first 10 days of therapy and AKI occurred in 21 patients (14.9%). No factors studied, including age, gender, obesity class, initial dose, SCr, or frequency were associated with accumulation. Conclusion Most patients with obesity experienced vancomycin accumulation within the first 10 days of therapy. Providers should be cautious when assessing a vancomycin concentration early in the treatment course. Disclosures All Authors: No reported disclosures

median weight was 112.7 kg ) and the median BMI was 36.8 kg/m 2 . The median total daily vancomycin dose at initiation was 28.7 mg/kg/day . Vancomycin accumulation occurred in 99 patients (61.1%) within the first 10 days of therapy and AKI occurred in 21 patients (14.9%). No factors studied, including age, gender, obesity class, initial dose, SCr, or frequency were associated with accumulation.
Conclusion. Most patients with obesity experienced vancomycin accumulation within the first 10 days of therapy. Providers should be cautious when assessing a vancomycin concentration early in the treatment course.
Disclosures. Methods. Four clinical STM isolates with MIN MICs 0.25 -1 mg/L were included. Both thighs of neutropenic ICR mice were inoculated with bacterial suspensions of 10 7 colony forming units (CFU)/mL. Mice received uranyl nitrate on Day -3 to provide predictable renal impairment. Two hours after inoculation, MIN or control was administered subcutaneously. Pharmacokinetic (PK) studies of 2.5, 25, 50, and 100 mg/kg were conducted. Previously reported protein binding of 78.1% was used to define free exposure. Dose ranging studies were conducted on all STM to assess in vivo activity over a range of MIN exposures. MIN total daily doses (TDD) of 10, 20, and 50 mg/kg were fractionated q24h, q12h, and q6h against a single STM to determine the PD index best correlated with reductions in CFU/mL. Efficacy was measured in log 10 CFU/thigh at 24h compared with 0h controls. Composite CFU data were fitted to an E max model to determine the fAUC/MIC exposure for stasis and 1 log 10 reduction.
Conclusion. These are the first data describing MIN PD against STM. Against these STM, MIN fAUC/MIC was the PD index best correlated with CFU reductions. The exposure thresholds defined in this study will be useful in designing optimal MIN dosing regimens for treating STM infections and re-assessment of the current susceptibility breakpoint.
The study was funded under FDA Contract 75F40120C00171. Background. Therapeutic drug monitoring (TDM) is paramount to optimize the safety and efficacy of vancomycin (VAN). In children, TDM is challenged by difficulty in obtaining venous samples, impeding timely sampling. We assessed the ability of volumetric absorptive microsampling (VAMS) as a novel, whole blood sampling technique to predict plasma VAN concentrations in plasma.
Methods. We conducted a prospective pilot study among critically ill children prescribed VAN for clinical care. Coincident with VAN TDM in plasma (P), we collected 20 µL of capillary whole blood (C) and venous/arterial whole blood (V) using VAMS. Paired VAMS-P samples drawn >5 mins apart and VAMS samples with over-or under-loaded filter tip on visual inspection were excluded. Plasma concentrations were measured via chemiluminescent immunoassay in the Chemistry Laboratory. VAMS C and V concentrations were measured using LC/MS in the Bioanalytic Core Laboratory. Plasma concentrations were predicted from whole blood VAMS with Passing-Bablok regression using 3 methods: 1) uncorrected VAMS measures, 2) hematocrit-corrected VAMS, and 3) lab-corrected VAMS (Figure 1). We then assessed bias, imprecision, and accuracy of plasma predictions from VAMS (C and V) as compared to coincident P concentrations for each technique (Figure 1). Figure 1. Methods for relating whole blood vancomycin concentrations collected via VAMS to plasma concentrations and measure to evaluate predictive performance.
Results. Paired samples were collected from 31 enrolled subjects (Figure 2), with a median age of 3.3 years (range 0.1-17.9). Measured P concentrations ranged from 4.6 -54.9 mg/L. 11 C samples (29%) and 3 V samples (10%) were excluded due to collection issues. Prediction results are shown in Figure 3. The 3 prediction techniques had similar performance characteristics, with each method displaying minimal bias (-0.4-2.0%) and reasonable imprecision (13.7-20.2%). The accuracy of prediction of P concentrations using VAMS was better for V than C samples.