755. Connecting the dots: Evaluation of Extended Interval Aminoglycoside Dosing Nomogram via Monte Carlo Simulation
Session: Poster Abstract Session: Antimicrobials: Treatment of HAI and Resistant Infections
Friday, October 4, 2013
Room: The Moscone Center: Poster Hall C
  • IDWeek 2013_0921_final.pdf (617.1 kB)
  • Background:

    With decreasing susceptibility of frequently prescribed antimicrobial agents, the reconsideration of the use of aminoglycosides (AGs) is warranted. Studies have shown that in using extended interval dosing, clinicians can maximize bactericidal efficacy while reducing toxicity. The Hartford Nomogram (HN) is the most frequently dosing nomogram used as it offers clinicians a simple solution of monitoring AGs therapy. However, controversy persists regarding its use in acute settings. The objective of this study is to examine the utility of the HN in therapeutic drug monitoring of AGs among critically ill patients with various stages of renal function via simulations.


    A Monte Carlo simulation study was conducted to assess the HN among critically ill patients in acute settings. The simulations were carried out in three groups of patients based on their creatinine clearance (≥60 ml/min, 40–59 ml/min, and 20–39 ml/min). One thousand values of elimination rate constant (Ke), representing 1000 patients, were randomly generated for each pair of concentration-time for each patient group. For each randomly generated Ke and its associated concentration-time point, Tmin, Cmax and targeted Cmin were calculated.


    The treatment interval is appropriate in 70%-80% of patients with creatinine clearance ≥40 ml/min when the HN recommends Q24h interval. Analyses show that the probability of achieving desired peak concentrations (Cmax between 18-23 µg/mL) ranges from 7% to 24%. The probability of Cmax greater than 23 µg/mL is highest in the Q36 and Q48 time intervals. In addition, for all three groups, probability of Cmax less than 18 is highest in the Q24 time interval. Finally, the accuracy of targeted peak concentration and drug free interval using the HN falls between 0.53% and 15% for patients with various kidney functions.


    In the era of multi-drug resistant-bacteria, creating the efficacious and safe dosing regimen is important while aiming to achieve higher concentrations; especially preventing underdosing for critically ill patients. The use of the HN may lead to underestimation of Cmax, although it does not pose safety concern. Due to the inter-variability among patients, individual PK evaluation should be considered for those patients with complicated condition.

    Whitney (Yu-Hui) Hung, PharmD, BCPS (AQ-ID), Pharmacy, Yale New Haven Hospital, New Haven, CT, Odaliz Abreu-Lanfranco, MD, Department of Medicine, Yale New Haven Hospital, New Haven, CT and Tai-Tsang Chen, PhD, Columbia University, New York, NY


    W. Hung, None

    O. Abreu-Lanfranco, None

    T. T. Chen, None

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