Donald P. Alexander

Optimizing Vancomycin Dosing through Pharmacodynamic Assessment Targeting Area under the Concentration-Time Curve/Minimum Inhibitory Concentration:

Because of its activity against multidrug resistant gram-positive organisms, vancomycin is one of the antimicrobials most utilized in health care systems worldwide. Despite its widespread use, application of the pharmacodynamic principles governing vancomycin efficacy are not frequently considered in contemporary clinical practice. Although the vancomycin trough serum concentration has been used historically to assess the adequacy of a prescribed dose, data validating that this practice leads to improved patient outcomes do not exist. Alternatively, both in vitro and clinical outcomes data demonstrate improved results when an area under the concentration-time curve/minimum inhibitory concentration (AUC/MIC) of 400 mcg•h/mL or greater is achieved. This article describes the process through which individualized vancomycin dosing regimens targeting an AUC/MIC of 400 mcg•h/mL or greater, rather than trough serum concentration, at the beside can be derived. The equations, methodology, thought processes, benefits, potential pitfalls, and practical applicability of this method are specifically examined. Obtaining the actual MIC value—not an interpretation—from the microbiology laboratory and/or the MIC distribution for Staphylococcus aureus within ones own institution is essential for implementation of this method. Although vancomycin dosing recommendations suggested in contemporary practice guidelines are likely adequate for most patients, using the methods described here may lead to improved clinical outcomes for nonstandard conditions in patients who are critically ill and would benefit from an individualized dosing approach.

Patient Variables Associated with Nafcillin Plasma Concentrations and Toxicity.

Primary objective: To retrospectively review nafcillin plasma concentrations (CNAF) and determine nafcillin clearance (CLNAF) in a diverse sample of patients treated with nafcillin administered as a continuous infusion. Secondary objective: To identify clinical variables associated with CLNAF and nafcillin‐related adverse drug reactions (ADRs).

Impact of a Multiplex PCR Assay for Bloodstream Infections With and Without Antimicrobial Stewardship Intervention at a Cancer Hospital

Abstract Implementation of Biofire FilmArray Blood Culture Identification Multiplex PCR panel (BCID) at a cancer hospital was associated with reduced time to appropriate antimicrobial therapy. Additional reductions were not observed when BCID was coupled with antimicrobial stewardship intervention.

981: EVALUATION OF MEROPENEM CONTINUOUS-INFUSION CLEARANCE IN BURN PATIENTS

www.ccmjournal.org Critical Care Medicine • Volume 46 • Number 1 (Supplement) Learning Objectives: Meropenem is a time-dependent, carbapenem antibiotic with a broad spectrum of activity that is used for treatment of multi-drug resistant (MDR) bacteria. Limited data of meropenem pharmacokinetics (PK) is available for patients with burn injuries, and no studies regarding meropenem PK/PD from burn centers in the United States are reported. Burn patients often exhibit increased non-renal and renal clearance and decreased protein binding. Due to altered PK in burn patients, we often administer time-dependent antibiotics as a continuous infusion (CI) to optimize pharmacodynamics (PD). Methods: This retrospective chart review included patients who received meropenem CI from January 1, 2008 to May 30, 2017 at the University of Utah Burn Center. We utilize a meropenem microbiological assay for PK analysis. Patients with an appropriately collected steady state level and no confounding antibiotics were included. Meropenem plasma clearance (CLtotal) was calculated using the infusion rate and plasma concentration. The primary objective was to assess meropenem plasma clearance to determine if dose adjustments are needed. Results: Twenty-one meropenem levels from 14 patients met inclusion criteria (Pediatric n = 4, Age: 1 to 10 years, weight: 10.9 to 44 kg; Adult n = 10, Age: 15 to 66 years, weight 50 to 119 kg; Total body surface area (TBSA): 21 to 70% partial and full thickness burns). Four undetectable meropenem levels were excluded. Treatment was for MDR Pseudomonas, Enterobacter, and Acinetobacter pneumonia and wound infections (MIC < 0.25 to 1 mcg/mL). Adult total daily doses were 2100 to 9000 mg, and 8 of 15 doses were greater than 4500 mg daily. Pediatric total daily doses were 89 to 333 mg/kg/day. No patients had renal insufficiency. Meropenem plasma concentrations were 5 to 37 mcg/ mL (median 15 mcg/mL). CLtotal for adult patients was 3.4 to 31.3 L/hr and for pediatric patients 9.7 to 34.3 L/hr/1.73 m2. Time above MIC was 100% for all patients. Four dose adjustments occurred. No adverse effects were observed. Conclusions: Large total daily doses were required for the majority of patients to optimize PD. A wide range of meropenem CI clearance was observed. PK analysis is recommended to guide dose adjustments. Further studies investigating factors that affect meropenem clearance in burn patients and correlation of levels with clinical outcomes are warranted.