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Background: Free online adaptive vancomycin dosing calculators are available to estimate area under the concentration-time curve (AUC), but the accuracy of predicting vancomycin AUC using these calculators compared with using a 2-point pharmacokinetic approach has not been described., Objective: To evaluate the accuracy of calculator-predicted AUC (cpAUC) using 4 free online calculators compared with reference AUC (rAUC), and to assess pharmacists' impressions of the ease of use., Methods: Vancomycin AUC was estimated using (1) the reference method via the Sawchuk-Zaske method and linear-logarithmic trapezoidal rule using 2 steady-state postdistributional vancomycin serum concentrations and (2) 4 free online vancomycin dosing calculators including ClinCalc, VancoPK, TDMx, and DMC. Accuracy was calculated by dividing cpAUC by rAUC. Ease of cpAUC estimation was determined by using a 10-point Likert scale., Results: All 4 calculators had a median cpAUC accuracy ranging from 89% to 110%. Concordance between cpAUC and rAUC determinations of AUC <400 and > 600 mg·h/L occurred 63.3% to 71.4% and 74.5% to 78.6% of the time, respectively. Pharmacist investigators agreed that ClinCalc and VancoPK calculators were easiest to use., Conclusion and Relevance: cpAUC accuracy varied among the 4 calculators, but all consistently identified patients with an rAUC <400 mg·h/L and an rAUC > 600 mg·h/L at comparable frequencies. All 4 calculators demonstrated some imprecision based on their wide 95% CIs and potential inaccuracies in predicting an rAUC <400 mg·h/L or an rAUC > 600 mg·h/L. Clin Calc and VancoPK were most user friendly based on our pharmacists' impressions.

Background: Severe sepsis and septic shock represent common presentations in the emergency department (ED) and have high rates of mortality. Guideline-recommended goals of care have been shown to benefit these patients, but can be difficult to provide., Objective: To determine whether the use of a premixed bag consisting of 2 g cefepime and 1 g vancomycin in 1000 mL of normal saline increases the probability of patients receiving Surviving Sepsis Campaign (SSC) recommendations for the initiation of antimicrobials and fluid challenge., Methods: This was a 6-month retrospective analysis conducted to determine the impact of an intervention on time to antimicrobials and fluid administration in patients with severe sepsis and septic shock. Patients presenting to the ED who received a diagnosis of severe sepsis or septic shock and were administered 2 antibiotics were eligible for inclusion. The primary outcome assessed was compliance with SSC recommendations for antibiotic and fluid goals within 3 hours of ED arrival., Results: A total of 160 patients were included. In the intervention group, 63.8% of patients met the primary outcome compared with 22.5% in the historical group (odds ratio = 2.32; 95% CI = 1.67-3.23). Time to administration of antibiotics was less with the combination antibiotic bag (CAB: median (IQR) = 72 (48-115) minutes; non-CAB: median (IQR) = 135 (102-244) minutes; P ≤ 0.001)., Conclusion: This intervention significantly increased the proportion of patients provided with SSC goals of care. Such interventions have not been reported previously and could be meaningful in the management of severe sepsis and septic shock.

Background: Guidelines support area-under-the-curve (AUC) monitoring for vancomycin dosing which may lower overall doses and reduce acute kidney injury (AKI). Objective: The aim of this study was to compare incidence of AKI across 3 vancomycin dosing modalities: AUC-targeted Bayesian pharmacokinetic software, AUC-targeted empiric dosing nomogram, and trough-guided dosing using clinical pharmacists' judgment. Methods: This retrospective study included adult patients with a pharmacy dosing consult who received ≥1 dose of vancomycin and ≥1 serum vancomycin level documented between January 1, 2018, and December 31, 2019. Patients with baseline serum creatinine ≥2 mg/dL, weight ≥100 kg, receiving renal replacement therapy, AKI prior to vancomycin therapy, or vancomycin ordered only for surgical prophylaxis were excluded. The primary analysis was incidence of AKI adjusted for baseline serum creatinine, age, and intensive care unit admission. A secondary outcome was adjusted incidence of an abnormal trough value (<10 or >20 μg/mL). Results: The study included 3459 encounters. Incidence of AKI was 21% for Bayesian software (n = 659), 22% for the nomogram (n = 303), and 32% for trough-guided dosing (n = 2497). Compared with trough-guided dosing, incidence of AKI was lower in the Bayesian (adjusted odds ratio [OR] = 0.72, 95% confidence interval [CI]: 0.58-0.89) and the nomogram (adjusted OR = 0.71, 95% CI: 0.53-0.95) groups. Compared with trough-guided dosing, abnormal trough values were less common in the Bayesian group (adjusted OR = 0.83, 95% CI: 0.69-0.98). Conclusion and Relevance: Study results suggest that use of AUC-guided Bayesian software reduces the incidence of AKI and abnormal trough values compared with trough-guided dosing. [ABSTRACT FROM AUTHOR]

Background: A vancomycin target of area under the curve to minimum inhibitory concentration (AUC:MIC) ratio ≥400 is recommended for treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Objective: To evaluate vancomycin total daily dose (TDD) achieving trough targets versus a calculated strategy achieving AUC targets based on body mass index (BMI). Methods: A retrospective cohort study was performed within a large hospital network. Patients with MRSA bacteremia were eligible if they received vancomycin with a steady-state trough (15-20 mg/L). Cockcroft-Gault was used to estimate creatinine clearance, calculating vancomycin clearance and AUC. Patients were stratified by BMI (less than/greater than 30 kg/m2). The primary outcome was vancomycin TDD for the trough-based strategy compared with an AUC-dosing strategy. Results: A total of 119 patients were included, including 51 (42.9%) and 68 (57.1%) patients with high- and low-BMI, respectively. The TDD for trough-based dosing (2390.76 ± 1224.59 mg) differed significantly from AUC-based dosing (1985.07 ± 616.18 mg) across the cohort (P = 0.0014). For patients with high BMI, there was a significant difference (P < 0.0001) in TDD between trough (2637.25 ± 1327.89 mg) versus AUC (1918.71 ± 625.89 mg) strategies. No difference in TDD between dosing strategies was observed among low-BMI patients. Across all patients, 46 (38.7%) experienced acute kidney injury (AKI); high-BMI patients experienced higher rates of AKI compared with low-BMI patients (54.9 vs 26.5%; P = 0.002). Conclusions and Relevance: An AUC-based dosing strategy may reduce vancomycin TDD required for MRSA bacteremia compared with trough-based dosing, particularly for patients with higher BMI. [ABSTRACT FROM AUTHOR]

Background: Various pharmacokinetic (PK) equations and software have been developed to individualize vancomycin dosing. However, the benefit of using any PK information to guide vancomycin dosing has not been fully elucidated. Objective: To appraise available evidence on the effectiveness and safety of individualized vancomycin dosing via PK tools. Methods: PubMed, EMBASE, the Cochrane Library, and 2 Chinese literature databases were searched through August 1, 2019. Randomized controlled trials (RCTs) and cohort studies that reported the PK and clinical outcomes of individualized vancomycin dosing versus empirical dosing were included. Pooled risk ratios (RRs) and mean differences were calculated for dichotomous and continuous outcomes, respectively. Results: A total of 21 studies involving 4346 patients were finally included, of which 3 were RCTs and 18 were cohort studies. Meta-analysis revealed that PK-guided vancomycin dosing significantly increased the attainment of target trough concentration (RR = 1.59; 95% CI = 1.49-1.70) and decreased the incidence of nephrotoxicity (RR = 0.57; 95% CI = 0.46-0.71). Additionally, the available evidence showed that target area under the curve/minimum inhibitory concentration attainment rate and time to target concentration could improve. However, the evidence on clinical outcomes was scarce, and no significant differences were detected in clinical response rate, microbiological eradication rate, mortality, and length of hospital stay between PK-guided vancomycin dosing and empirical dosing strategies. Conclusion and Relevance: Individualized vancomycin dosing via PK tools significantly increases the attainment of target trough concentration and decreases the incidence of nephrotoxicity. Evidence on clinical effectiveness was limited and showed no significant benefit. Further well-designed studies are warranted to assess its clinical effectiveness and inform routine care. [ABSTRACT FROM AUTHOR]

We observed poor uptake of vancomycin AUC monitoring with the use of first-order PK analytic equations, with only 25% of regimens meeting criteria having AUC monitoring performed. Our institutional vancomycin monitoring guidelines recommend AUC monitoring for patients with severe MRSA infections, excluding patients on hemodialysis, those with unstable/acutely changing renal function, or if lab draws must be limited. [Extracted from the article]