Measuring Antimicrobial Use: The Way Forward

Received 18 November 2006; accepted 20 November 2006; electronically published 22 January 2007. Reprints or correspondence: Dr. Dominique L. Monnet, Antimicrobial Resistance Surveillance Unit, National Center for Antimicrobials and Infection Control, Statens Serum Institut, Artillerivej 5, Copenhagen DK-2300, Denmark (dom@ssi.dk). Clinical Infectious Diseases 2007; 44:671–3 2007 by the Infectious Diseases Society of America. All rights reserved. 1058-4838/2007/4405-0007$15.00 DOI: 10.1086/511649 In 1991, Gerding et al. [1] published the results of their 10-year experience with aminoglycoside use and emergence of aminoglycoside resistance at the Minneapolis Veterans Affairs Medical Center. In this study on the relationship between antimicrobial use and bacterial resistance, consumption data were obtained from pharmacy records and reported as the number of patient-days (of antimicrobial use) per quarter. During about the same time in Europe, hospitals started to report similar data, but they chose to express antimicrobial use as a number of defined daily doses (DDDs) controlled for the population at risk of receiving antimicrobials (e.g., per 100 occupied bed-days or patient-days) [2–4]. The DDD is a measurement unit that was developed by Norwegian researchers together with the Nordic Council on Medicines (Uppsala, Sweden) and was first used in a report in 1976 [5]. The DDD is the assumed average maintenance dose per day for a drug in its main indication for adults. It is a measurement unit to be used during drug use studies and does not necessarily reflect the recommended or prescribed daily dose for individual patients or specific patient groups. Norwegian researchers also developed an Anatomical Therapeutic Chemical (ATC) classification for medicines by modifying and extending the European Pharmaceutical Market Research Association classification system [5]. In 1981, the World Health Organization (WHO) regional office for Europe recommended the ATC/DDD system for international drug use studies. To coordinate activities in the field, a WHO Collaborating Centre for Drug Statistics Methodology was established in Oslo in 1982. Applications for additions or modifications of ATC codes and DDDs are made by users of the system to the WHO Collaborating Centre. These applications are submitted by the WHO Collaborating Centre to a WHO International Working Group for Drug Statistics Methodology, established in 1996, which is in charge of maintaining the ATC/DDD system. The 12 members of this group are experts appointed by the WHO headquarters to represent a wide range of professional backgrounds and the 6 WHO global regions. Extensive information on the ATC/DDD system is available at the WHO Collaborating Centre Web site [5]. Once aware of the DDD methodology, researchers in the United States quickly adopted the DDDs to report hospital antimicrobial use data [6–9]. However, these researchers omitted the fact that, for each antimicrobial, the DDD is a WHO-assigned, international measurement unit, rather than just a methodology to adjust for differences in daily dosages between various antimicrobials when calculating antimicrobial use. This unfortunately led to different “DDDs” being used in Europe and the United States. Availability of the ATC classification and the DDD definitions without charge on the WHO Collaborating Centre Internet home page [10] and a free tool for calculating antimicrobial use [11] have increased awareness about the ATC/DDD system. The WHO-assigned DDDs were used for most of the recent international or multicenter surveillance studies, both in Europe and in the United States, as well as in Australia [12–18]. The Infectious Diseases Society of America Practice Guideline on antimicrobial stewardship recommends monitoring antimicrobial use by the number of DDDs [19]. Although increased awareness and endorsement of the WHO-assigned DDDs contribute to standardization—and, therefore, comparability—of the reported rates, they also emphasize the limitations of this measurement unit, especially for antimicrobial use in hospitals. In this issue of Clinical Infectious Diseases, Polk et al. [20] discuss the limitations of the WHO-assigned DDDs and report on discrepancies between these DDDs and the number of days of therapy, which they obtained from patient records. As correctly mentioned by Polk and col-