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Systemic Antifungal Drug Use in Belgium— Received: 7 October 2018 | Revised: 28 March 2019 | Accepted: 14 March 2019 DOI: 10.1111/myc.12912 ORIGINAL ARTICLE Systemic antifungal drug use in Belgium—One of the biggest antifungal consumers in Europe Berdieke Goemaere1 | Katrien Lagrou2,3* | Isabel Spriet4,5 | Marijke Hendrickx1 | Eline Vandael6 | Pierre Becker1 | Boudewijn Catry6,7 1BCCM/IHEM Fungal Collection, Service of Mycology and Aerobiology, Sciensano, Summary Brussels, Belgium Background: Reports on the consumption of systemic antifungal drugs on a national 2 Department of Microbiology and level are scarce although of high interest to compare trends and the associated epi- Immunology, KU Leuven, Leuven, Belgium 3Clinical Department of Laboratory demiology in other countries and to assess the need for antifungal stewardship Medicine, National Reference Centre for programmes. Mycosis, University Hospitals Leuven, Leuven, Belgium Objectives: To estimate patterns of Belgian inpatient and outpatient antifungal use 4Department of Pharmaceutical and and provide reference data for other countries. Pharmacological Sciences, KU Leuven, Methods: Consumption records of antifungals were collected in Belgian hospitals Leuven, Belgium between 2003 and 2016. Primary healthcare data were available for the azoles for 5Pharmacy Department, University Hospitals Leuven, Leuven, Belgium the period 2010-2016. 6 Healthcare‐Associated Infections and Results: The majority of the antifungal consumption resulted from prescriptions of Antimicrobial Resistance, Sciensano, Brussels, Belgium fluconazole and itraconazole in the ambulatory care while hospitals were responsible 7Faculty of Medicine, Université Libre de for only 6.4% of the total national consumption and echinocandin use was limited. Bruxelles (ULB), Brussels, Belgium The annual average antifungal consumption in hospitals decreased significantly by Correspondence nearly 25% between 2003 and 2016, due to a decrease solely in non-university hos- Berdieke Goemaere, Sciensano, Mycology pitals. With the exception of specialised burn centres, antifungals are mostly con- and Aerobiology, Brussels, Belgium. Email: [email protected] sumed at ICUs and internal medicine wards. A significant decline was also observed in the consumption of azoles in primary health care, attributed to itraconazole. The Funding information Sciensano major part of azoles was prescribed by generalists followed by dermatologists. Conclusions: In spite of the downward trend in annual use of systemic antifungal drugs, Belgium remains one of the biggest consumers in Europe. KEYWORDS antifungal agents, hospital, prescription rates, primary care, public health, surveillance 1 | INTRODUCTION antifungals, therapeutic options have been extended and a variety of agents from four different classes can currently be addressed for Paralleling an increasing population of immunocompromised pa- the treatment of fungal infections: polyenes, azoles, echinocandins tients during the last decades, opportunistic fungal infections and flucytosine. Furthermore, empirical therapy in high-risk patients gained major importance in health care, resulting in a rise in the significantly impacts consumption as illustrated by the high prescrip- 5-7 consumption of antifungal drugs.1-4 With the introduction of new tion of antifungal drugs in ICUs and haematology-oncology units. *FECMM (Fellow of the European Confederation of Medical Mycology) Mycoses. 2019;1–9. wileyonlinelibrary.com/journal/myc © 2019 Blackwell Verlag GmbH | 1 2 | GOEMAERE ET AL. The consumption of antifungals also influences the distribution for the period 2003-2016 in hospitals and also in DDD/1000 inhab- of microbial species and reduces the susceptibility of target patho- itants per day (DID) for the period 2010‐2016. gens.8-12 In order to follow up trends and to minimise antifungal A total of 105 acute care hospitals (with slightly varying partic- selective pressure, consumption monitoring and antifungal steward- ipation over years, Table S1) provided consumption data annually. ship approaches should be implemented on a local and on a national Data were available to classify the type of the hospital, the hospital- level.4,6,13 isation unit and the antimicrobial agent at ATC level five. Annual con- Geographical differences in fungal species distribution and as- sumption was expressed as the mean of sum of the antifungal usage sociated infections may influence the choice of antifungal therapy. per hospital for the year, unit and agent considered. Hospitals were The latter should be adapted according to the local epidemiology of classified according to teaching level: university hospitals (tertiary fungal pathogens. Hence, it is appropriate to outline the trends in hospitals, n = 7) and non‐university hospitals (n = 98). Consumption antifungal consumption on different geographical scales. data of the following hospitalisation units were included in the anal- Limited data exist on the consumption of systemic antifungal drugs yses: surgery, internal medicine, geriatrics, paediatrics, intensive and on a national level. Data often remain limited to the hospital sector or non-intensive neonatology, maternity, infectious diseases, burn unit, to a specific hospital unit such as the ICU (due to a high level of con- ICUs and specialised care. A separate analysis was performed on the sumption).3,7,14,15 Some studies define the consumption according to consumption data of the internal medicine (including the haematol- locally used doses (prescribed or recommended daily doses), reflect- ogy‐oncology unit) and the ICUs because highest consumptions gen- ing better actual prescriptions but they are unsuitable for international erally occur in these units.19 comparison.3,5 Other studies do not distinguish between consumption For the primary healthcare sector, national data concerning in hospitals versus primary care or report sales data, not adequately azoles for systemic use (J02AB, J02AC) were available for the pe- expressing the intensity of drug use (treatment incidence).16 riod 2010‐2016 and expressed in DID. Azoles for systemic use are This study aims to provide nationwide reference data (for bench- only available on prescription in Belgium. Consumption data were marking) by evaluating systemic antifungal consumption patterns in based on all outpatient drug prescriptions delivered by public phar- both the ambulatory and hospital care sectors in Belgium. Regarding macies, reimbursed and provided by INAMI‐RIZIV and validated by the latter, separate analyses were performed on university and non- PharmaNet. Data were available by type of prescriber (specialism) university hospitals and data were also stratified by type of hospital up to ATC level five. Patient gender was also available for ambulant wards (units). Consumption was expressed in defined daily doses prescriptions. The size of the Belgian population by year was pro- (DDD)/1000 patient‐days (hospitals) and in DDD/1000 inhabitants vided by the Belgian Statistical Office and expressed as the number per day (ambulant and hospitals). of inhabitants at January the first of that year.20 Associated costs were also available with a distinction between costs for the patients and costs for the social security system. 2 | MATERIAL AND METHODS All data were handled using Microsoft Excel software, and sta- tistical analyses were performed using the Stata software (StataSE National inpatient consumption data on antifungals for systemic 14, Stata Corp. 2013, College Station, Texas). Trends of antifungal use (J02) in the hospital sector (numerator) and number of pa- consumption over time were evaluated with the Mann‐Kendall test. tient‐days (denominator) were based on reimbursement data pro- The Wilcoxon signed-rank test was used to compare differences be- vided by the Belgian National Institute for Health and Disability tween university and non-university hospitals as well as between Insurance (INAMI‐RIZIV) and validated by the Healthcare‐ hospital units. P values less than 0.05 were considered statistically Associated Infections and Antimicrobial Resistance service significant. at Sciensano, Belgium.17 In 2016, approximately 98.6% of the Belgian population had a health insurance equalising reimburse- 3 | RESULTS ment. Data on not reimbursed use of antifungals were not avail- able. Consumption data were categorised according to the World 3.1 | National inpatient data: hospital‐wide Health Organization (WHO) Anatomical Therapeutic Chemical consumption (ATC) classification index, and the defined daily doses (DDD) was applied as unit of measurement to allow standardised and interna- Figure 1 shows an overview of the annual average consumption of tional comparisons.18 systemic antifungals (J02) in Belgian hospitals between 2003 and The following antifungal drugs were available in Belgium, and 2016. The annual average hospital consumption of all systemic their consumption data were evaluated in this study: amphoteri- antifungal agents decreased significantly (P < 0.05) by nearly 25% cin B (J02AA01) (the conventional formulation was available until between 2003 (37.72 DDD/1000 patient‐days) and 2016 (28.42 2010), flucytosine (J02AX01), ketoconazole (J02AB02), fluconazole DDD/1000 patient‐days). The latter is not equal to the sum of the (J02AC01), itraconazole (J02AC02), voriconazole (J02AC03), po- annual average consumption of the different subclasses because of saconazole (J02AC04), caspofungin (J02AX04) and anidulafungin the variation in the use of these subclasses per hospital (Table
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