WHO RECOMMENDATIONS

3. WHO RECOMMENDATIONS

At a symposium in Oslo in 1969 entitled, The Consumption of Drugs, it was agreed that an internationally accepted classification system for drug con- sumption studies (not just antibiotics) was needed. At the same symposium the Drug Utilisation Research Group (DURG) was established by the WHO and charged with the task of developing internationally applicable methods for drug utilisation research.

In collaboration with the Norwegian Medicinal Depot (NMD), DURG updated the existing European Pharmaceutical Market Research Association classification system and developed the system now known as the Anatomical Therapeutic Chemical (ATC) classification system. From there, the unit of measurement known as the defined daily dose, or DDD, was developed for use in conjunction with the ATC system. In 1982, the WHO recommended the ATC/DDD system for international drug utilisation studies and introduced the WHO Collaborating Centre for Drug Statistics Methodology, based in Oslo, as

a central body responsible for coordinating the use of the methodology. This centre is now responsible for classifying drugs according to the ATC system and setting DDDs.

3.1. ATC classification

In the ATC system, drugs are divided into 14 main groups according to the organ or system on which they act and their chemical, pharmacological, and therapeutic properties (WHO Collaborating Centre, Oslo, 2002a, b). ATC class “J” includes “general anti-infectives for systemic use” and class “J01” deals specifically with “antibacterials for systemic use.” Details of the J01 subclasses can be found in Table 1. Users of the ATC classification system tend only to quote antibiotic consumption for the J01 class. This however, does not necessarily reflect total consumption, as a few antibiotics have been placed in classes other than J01. For example, antibiotics given orally for decon- tamination of the digestive tract (including vancomycin) or intestinal anti- infectives have been placed in ATC group A07A and nitroimidazole derivatives to treat protozoal diseases are in ATC group P01AB. This is a relatively minor drawback of the system and is currently being addressed by the WHO.

Quantitative Measurement of Antibiotic Use 109

Table 1. Anatomical Therapeutic Chemical (ATC) classification of antibiotics

J ANTIINFECTIVES FOR SYSTEMIC USE J01 ANTIBACTERIALS FOR SYSTEMIC USE

J01A TETRACYCLINES J01B AMPHENICOLS J01C BETA-LACTAM ANTIBACTERIALS, PENICILLINS

J01CA Penicillins with extended spectrum J01CE Beta-lactamase sensitive penicillins J01CF Beta-lactamase resistant penicillins J01CG Beta-lactamase inhibitors J01CR Combinations of penicillins, incl. beta-lactamase inhibitors

J01D OTHER BETA-LACTAM ANTIBACTERIALS J01DA Cephalosporins and related substances J01DF Monobactams J01DH Carbapenems

J01E SULFONAMIDES AND TRIMETHOPRIM J01EA Trimethoprim and derivatives J01EB Short-acting sulfonamides J01EC Intermediate-acting sulfonamides J01ED Long-acting sulfonamides J01EE Combinations of sulfonamides and trimethoprim, incl. derivatives

J01F MACROLIDES, LINCOSAMIDES AND STREPTOGRAMINS J01FA Macrolides J01FF Lincosamides J01FG Streptogramins

J01G AMINOGLYCOSIDE ANTIBACTERIALS J01GA Streptomycins J01GB Other aminoglycosides

J01M QUINOLONE ANTIBACTERIALS J01MA Fluoroquinolones J01MB Other quinolones

J01R COMBINATIONS OF ANTIBACTERIALS J01X OTHER ANTIBACTERIALS

J01XA Glycopeptide antibacterials J01XB Polymyxins J01XC Steroid antibacterials J01XD Imidazole derivatives J01XE Nitrofuran derivatives J01XX Other antibacterials

110 Fiona M. MacKenzie and Ian M. Gould

3.2. Defined daily doses (numerator)

The DDD (expressed in grams) is the assumed average maintenance dose per day for a drug used for its main indication in a 70 kg adult and will only be assigned to drugs with an ATC code. The WHO emphasises that the DDD is a unit of measurement and does not necessarily reflect the recommended or pre- scribed daily dose—although in many cases it does. The WHO also states that drug consumption data presented in DDDs only gives an estimate of consump- tion and not an exact picture of actual use. DDDs do however, provide an inter- nationally fixed unit of measurement independent of price and formulation enabling investigators to assess trends in drug consumption and to perform comparisons between groups. An in-depth discussion of the assignment of DDDs can be found on the WHO Collaborating Centre for Drug Statistics Methodology website and in their publications (WHO Collaborating Centre, Oslo, 2002a, b). It should be noted that DDDs are continuously being revised and anybody can request changes to the ATC and DDD systems. Justified requests are fully discussed and changes made if warranted. New and updated ATC/DDD lists are subsequently published at the start of each year. One of the main downsides of the DDD system is that it cannot be applied to children, given that the DDDs relate to an average adult.

3.3. Denominator data

Antibiotic consumption data expressed as total DDDs used is of little value unless expressed with an appropriate denominator. It is conventional (and use- ful) to standardise the denominator for measurement of antibiotic use to further facilitate comparisons with other publications. In the community, consumption is commonly expressed as DDDs/1,000 inhabitant-days whereas the WHO rec- ommends DDDs/100 bed-days be used in the hospital. It has however, been suggested that hospital data be expressed as DDDs/1,000 bed-days in order to allow for easier comparison between hospital and community. Inevitably, the bed-days are an approximation as days of admission and discharge are not full days but we believe this has become the international convention. Number of admissions may be a better measurement of hospital activity in view of the shortening length of hospital stay but it is not generally used.

3.4. Theory into practice

It cannot be overemphasised that for effective data comparison and bench- marking, the ATC/DDD classification system must be used without modifica- tion. The process of expressing the consumption of different antibiotics and

Quantitative Measurement of Antibiotic Use 111 classes of antibiotics as DDD/100 bed-days could be a complicated one if the

investigator were to work up the system of calculation from first principles using the basic information supplied by the WHO Collaborating Centre for Drug Statistics Methodology. Fortunately, all the hard work has already been undertaken and the Antibiotic Consumption Calculator (ABC Calc) simplifies the whole procedure (Monnet, 2003).