Dataset Information

A Quasi-Experiment To Study the Impact of Vancomycin Area under the Concentration-Time Curve-Guided Dosing on Vancomycin-Associated Nephrotoxicity.

ABSTRACT: Evidence suggests that maintenance of vancomycin trough concentrations at between 15 and 20 mg/liter, as currently recommended, is frequently unnecessary to achieve the daily area under the concentration-time curve (AUC₂₄) target of ?400 mg · h/liter. Many patients with trough concentrations in this range have AUC₂₄ values in excess of the therapeutic threshold and within the exposure range associated with nephrotoxicity. On the basis of this, the Detroit Medical Center switched from trough concentration-guided dosing to AUC-guided dosing to minimize potentially unnecessary vancomycin exposure. The primary objective of this analysis was to assess the impact of this intervention on vancomycin-associated nephrotoxicity in a single-center, retrospective quasi-experiment of hospitalized adult patients receiving intravenous vancomycin from 2014 to 2015. The primary analysis compared the incidence of nephrotoxicity between patients monitored by assessment of the AUC₂₄ and those monitored by assessment of the trough concentration. Multivariable logistic and Cox proportional hazards regression examined the independent association between the monitoring strategy and nephrotoxicity. Secondary analysis compared vancomycin exposures (total daily dose, AUC, and trough concentrations) between monitoring strategies. Overall, 1,280 patients were included in the analysis. After adjusting for severity of illness, comorbidity, duration of vancomycin therapy, and concomitant receipt of nephrotoxins, AUC-guided dosing was independently associated with lower nephrotoxicity by both logistic regression (odds ratio, 0.52; 95% confidence interval [CI], 0.34 to 0.80; P = 0.003) and Cox proportional hazards regression (hazard ratio, 0.53; 95% CI, 0.35 to 0.78; P = 0.002). AUC-guided dosing was associated with lower total daily vancomycin doses, AUC values, and trough concentrations. Vancomycin AUC-guided dosing was associated with reduced nephrotoxicity, which appeared to be a result of reduced vancomycin exposure.

SUBMITTER: Finch NA

PROVIDER: S-EPMC5700348 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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A Quasi-Experiment To Study the Impact of Vancomycin Area under the Concentration-Time Curve-Guided Dosing on Vancomycin-Associated Nephrotoxicity.

Finch Natalie A NA Zasowski Evan J EJ Murray Kyle P KP Mynatt Ryan P RP Zhao Jing J JJ Yost Raymond R Pogue Jason M JM Rybak Michael J MJ

Antimicrobial agents and chemotherapy 20171122 12

Evidence suggests that maintenance of vancomycin trough concentrations at between 15 and 20 mg/liter, as currently recommended, is frequently unnecessary to achieve the daily area under the concentration-time curve (AUC<sub>24</sub>) target of ≥400 mg · h/liter. Many patients with trough concentrations in this range have AUC<sub>24</sub> values in excess of the therapeutic threshold and within the exposure range associated with nephrotoxicity. On the basis of this, the Detroit Medical Center swi ...[more]

PMID: 28923869

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Project description:AIM:To develop a vancomycin population pharmacokinetic model and assess the probability of attaining a pharmacodynamic target associated with clinical and microbiological success, a ratio of the 24-hour area under the concentration-time curve to the minimum inhibitory concentration (MIC) ? 400, in a 5-year clinical cohort of preterm and term neonatal patients with late-onset staphylococcal sepsis. METHODS:Therapeutic drug monitoring data were obtained from septic neonates with ?1 vancomycin concentration(s) from January 2006 to September 2011. Only neonates with a postnatal age of >72 hours and a positive microbiological culture were included. Population pharmacokinetic model was developed using nonlinear mixed effects modeling (NONMEM 7.2). Eleven demographic characteristics were evaluated as covariates. Probabilities of achieving the pharmacodynamic target were evaluated. RESULTS:A 1-compartment model with first-order elimination was constructed from 528 vancomycin concentrations collected from 152 preterm and term neonates. Body weight, creatinine clearance (CL), and postmenstrual age were identified as significant covariates. Estimated vancomycin CL and volume of distribution for typical neonates were 0.068 ± 0.03 L·h·kg and 0.62 ± 0.13 L/kg, respectively. Coagulase-negative staphylococci (85.5%) and Staphylococcus aureus (14.5%) were the common pathogenic organisms. The distribution of vancomycin MIC breakpoints was composed of approximately 70% MIC breakpoint of ?2 mcg/mL. Approximately 54% of neonates, with a median serum creatinine concentration of 0.44 mg/dL, achieved the target ratio of 24-hour area under the concentration-time curve to the MIC ? 400 with a median daily dose of 30 (interquartile range, 21-42) mg/kg. CONCLUSIONS:Body weight, creatinine CL, and postmenstrual age significantly influenced vancomycin CL. The current vancomycin doses are acceptable at MICs ?1 mcg/mL because they are likely to achieve the pharmacodynamic target in the majority of neonatal patients, although higher doses may be considered for more resistant staphylococcal infections.

Dataset Information

A Quasi-Experiment To Study the Impact of Vancomycin Area under the Concentration-Time Curve-Guided Dosing on Vancomycin-Associated Nephrotoxicity.

Publications

A Quasi-Experiment To Study the Impact of Vancomycin Area under the Concentration-Time Curve-Guided Dosing on Vancomycin-Associated Nephrotoxicity.

Similar Datasets

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