Measuring Antimicrobial Utilization of Gram-Negative (GN) Agents in the Era of Pharmacodynamic Dosing: Days of Therapy (DOT) Are Significantly Different from Defined Daily Doses (DDD)

Background: Antimicrobial stewardship programs often track trends in hospital-level utilization of antimicrobials (ABX). In order to compare different ABX against each other, the World Health Organization (WHO) has identified Defined Daily Doses (DDD) for each ABX in order to standardize across different dosing regimens for different agents. However, this is problematic when ABX are dosed differently from the WHO standard. Recently Days of Therapy (DOT) has been suggested as an alternative. At our institution, dosing for gram-negative agents has been modified based on pharmacokinetic (PK)/pharmacodynamic (PD) literature; cefepime (CPM), and sometimes meropenem, are often prescribed at higher doses (e.g., 2 grams every 8 hours) based on site of infection and/or higher minimum inhibitory concentrations.

Objective:

Compare ABX use of our most common broad-spectrum GN agents using DDD and DOT.

Methods:

Hospital use of piperacillin/tazobactam (P/T), cefepime (CPM), and carbapenems (imipenem and meropenem [I/M]) were calculated quarterly from 2007 first quarter  to 2009 second quarter, using DDD/1000 patient (pt) days and DOT/1000 pt days.  Data were calculated utilizing programs developed within Excel and Access platforms. Our dosing practices for these agents were translated into logic rules to automate calculations of DOT from our pharmacy database. Descriptive statistics were performed.  

Results:

Using either DDD or DOT (per 1000 pt days), P/T was the most commonly used agent, and numbers were not significantly different by either method (mean 150 vs 156 respectively, p = ns). Usage did not significantly vary over time. By contrast, for I/M, DDDs showed that use increased in 2008-9 compared to 2007 (mean 39.5/1000 pt days compared to 29.5/1000 pt days, p=0.006). However, DOTs revealed that use remained the same (mean 31.4 vs 32.6, p=ns). For CPM, the difference between DDD and DOT was more striking. By DDD, in 2008-9, CPM appeared to double from 2007, with a mean of 44.1/1000 pt days up from 19/1000 pt days (p<0.0001). However, DOTs revealed that use remained the same (mean 21.1 vs 22.3, p=ns). Whereas DDDs suggested that CPM use had outstripped I/M use by early 2008, in reality, I/M use remains more prevalent than CPM as demonstrated by DOTs.

Conclusions:

The need to measure ABX utilization to evaluate trends is essential. The DDD metric does not account for dosing practices that diverge from the WHO standard, nor for changes in dosing practices according to new PK/PD principles. By using DDDs, we assumed that CPM use had increased dramatically and overtaken I/M use, whereas a comparison with DOTs showed that it was merely due to an increase in dosing. Hospitals should convert to DOT/1000 pt days as the preferred measurement for ABX use, especially as dosing practices are shifting based on increasing ABX resistance and new PK/PD data.