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Association Between Antibiotic Sales and Public Campaigns for Their Appropriate Use
To the Editor: Two public campaigns for more rational use of antibiotics were organized in Belgium in 2000-2001 and 2001-2002 with a goal of reducing overuse and misuse of antibiotics in the community. We assessed their effectiveness with a time-series analysis that examined changes in antibiotic sales, accounting for the confounding effect of the seasonal variation of influenza-like illnesses (ILIs).
Methods
Each 3-month campaign concentrated on simple messages, together with a series of specific answers on topics of interest, that were conveyed through booklets, handouts, posters, prime-time television spots, and Web sites.1 Examples included "Use antibiotics less frequently but better"; "Save antibiotics, they may save your life"; and "Talk to your Doctor, Talk to your Pharmacist." Monthly outpatient antibiotic use in the community was estimated for the 1996-2002 period by extrapolation from sales data that covered 80.1% of all community pharmacies and 76.1% of the population. Sales data were converted to defined daily doses (DDDs).2 This unit is the assumed average maintenance dose per day for a drug used in adults for its main indication as defined by the World Health Organization; it allows for direct comparisons of drug use over time and place. National yearly gross antibiotic sales data were obtained from Intercontinental Marketing Services (IMS-Health) over the 1996-2002 period. In Belgium, antibiotics are available by prescription only.
Influenza-like illness was defined as flu-like symptoms: fever, myalgia, and respiratory symptoms, with sudden onset. Monthly indices of ILIs over the 1996-2002 periods were provided by the Belgian Scientific Institute of Public Health.3 To control for the seasonal influence of ILIs, an ARIMA transfer function model4 was built, with the output variable corresponding to antibiotic sales data (in DDDs), and the input variables corresponding to the ILI index and 2 intervention variables (1 for each campaign).
Results
Total antibiotic sales decreased 11.7% and 9.6% (in DDDs) during the 2000-2001 and the 2001-2002 December-March periods, respectively, compared with the same months in 1999-2000. However, there was an upsurge of antibiotic consumption with each seasonal peak of ILI index across the entire 1996-2002 period (Pearson correlation coefficient, 0.81; P<.01 [2-tailed]), and the 2000-2001 winter campaign period had a relatively low ILI index (Figure 1). The sales variation due to ILI amounted to 447 459 (SD, 38 950) DDDs per unit of ILI index.
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Figure 1. Seasonal Variation of Monthly Outpatient Antibiotic Sales and of Monthly Indices of Influenza-like Illnesses in Belgium, January 1996-July 2002
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After controlling for the influence of ILI, the global reduction in antibiotic sales for the 2000-2001 and the 2001-2002 campaigns periods was 6.5% (P<.05) and 3.4% (NS), respectively (Figure 2). Both campaigns had their maximal effect at the time of the peak of ILI. Data from IMS-Health (uncorrected for seasonal variations of ILI) showed a yearly antibiotic sales decrease of 5.3% (in DDDs) between 2000 and 2002, in contrast to a 2.9% increase for the 1997-1999 period. The 2 campaign periods were associated with an overall decrease of 1 354 518 (SD, 449 646) and of 1 195 290 (SD, 592 072) DDDs, respectively.
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Figure 2. Monthly Change in Antibiotic Sales Controlled for Influenza-like Illnesses During Each Campaign (December-February) and the Following Month (March)
Residual seasonal autoregressive terms: lag period, 12 months; estimated coefficient: 0.83 [SE, 0.06]; constant: 7 459 075 (SD, 431 387) defined daily doses/mo. The P values are indicated for the months and campaigns for which the changes were statistically significant.
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Comment
The level of antibiotic resistance of typical human pathogens is correlated with the rate of antibiotic use in the community.5 Overuse and misuse of antibiotics in the outpatient setting is commonly observed in countries or communities where consumption is great,6 and Belgians are among the high consumers in Europe.7 The present study shows that antibiotic sales are strongly linked to the incidence of ILI, for which the systematic use of antibiotics is not indicated in the general population. Our campaigns were associated with a reduction of antibiotic sales beyond what would merely result from interyear differences in the incidence of ILI. Public campaigns, therefore, may constitute a useful complement to other actions aimed at reducing antibiotic overconsumption. It remains to be seen, however, whether a reduction of antibiotic sales of the magnitude observed will help to curb the steady increase in resistance of pathogens in the community.
 Deceased.
Drs Bauraind, Hendrickx, Goossens, Tulkens, and Verbist are members of the Belgian Antibiotic Policy Coordination Committee (BAPCOC).
Funding/Support: The BAPCOC undertook the campaigns with the support of the Federal Services of Public Health and of Social Affairs, and the French, Flemish and German Communities of Belgium. IMS-Health Belgium kindly provided us with gross sales data of antibiotics in Belgium for the 1996-2003 period.
Role of the Sponsor: All direct costs of the campaigns were paid by the Ministry of Social Affairs (present denomination: Public Federal Service for Social Security and Public Institutions of Social Security). Scientific help was provided through the specialized institutions of the Belgian State as needed. The final organization of the campaigns and their evaluation was done by the ad hoc workgroup of the BAPCOC.
Isabelle Bauraind, MD
Federal Public Service for Health Security of the Food Chain and Environment
Brussels, Belgium
José-Maria Lopez-Lozano, MD
Unit of Preventive Medicine
Hospital Vega Baja
Orihuela, Alicante, Spain
Arielle Beyaert, PhD
Department of Quantitative Methods for Economics
Universidad de Murcia
Murcia, Spain
Jean-Louis Marchal, PhD;
Bruno Seys, MD
Belgian Institute of Pharmaco-epidemiology
Brussels, Belgium
Fernande Yane, MD;
Erik Hendrickx, MD
Scientific Institute of Public Health
Brussels, Belgium
Herman Goossens, MD, PhD
Laboratory of Microbiology
Universiteit Antwerpen
Antwerp, Belgium
Paul M. Tulkens, MD, PhD
tulkens{at}facm.ucl.ac.be
Cellular and Molecular Pharmacology Unit
Université Catholique de Louvain
Brussels, Belgium
Ludo Verbist, MD, PhD
Laboratory of Microbiology
University Hospital
Katholieke Universiteit Leuven
Louvain, Belgium
1. Belgian National Campaign for Appropriate Use of Antibiotics Web site. Available at: http://www.antibiotiques.org. Accessed September 30, 2004.
2. WHO Collaborating Centre for Drug Statistics Methodology Web site. Available at: http://www.whocc.no/atcddd/. Accessed September 30, 2004.
3. Snacken R, Lion J, Van Casteren V, et al. Five years of sentinel surveillance of acute respiratory infections (1985-1990): the benefits of an influenza early warning system. Eur J Epidemiol. 1992;8:485-490.
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4. Pankratz A. Forecasting With Dynamic Regression Models. New York, NY: Wiley; 1991.
5. Bronzwaer SL, Cars O, Buchholz U, et al. A European study on the relationship between antimicrobial use and antimicrobial resistance. Emerg Infect Dis. 2002;8:278-282.
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6. Hooton TM, Levy SB. Antimicrobial resistance: a plan of action for community practice. Am Fam Physician. 2001;63:1087-1098.
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7. Cars O, Molstad S, Melander A. Variation in antibiotic use in the European Union. Lancet. 2001;357:1851-1853.
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Letters Section Editor: Robert M. Golub, MD, Senior Editor.
JAMA. 2004;292:2468-2470.
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