1 National Center for Antimicrobials and Infection Control and 2 Biostatistics Unit, Statens Serum Institut, Copenhagen, Denmark
Received 29 March 2004; returned 31 May 2004; revised 4 October 2004; accepted 5 October 2004
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Methods: Data on the number of WHO defined daily doses (DDD) were obtained from the Danish Medicines Agency. Data on the number of bed-days were obtained from the National Board of Health. We calculated antimicrobial consumption in hospitals as the number of DDD per 100 bed-days for all antibacterials for systemic use i.e. group J01 of the Anatomical Therapeutic Chemical (ATC) classification and for classes of this group.
Results: During 19972001, antimicrobial use in hospitals in Denmark significantly increased by 18%, from 38.0 to 44.8 DDD per 100 bed-days (P < 0.005). Most of this increase (55%) was attributed to an increase in consumption of commonly used classes of antimicrobials, mainly penicillins with extended spectrum (ATC group J01CA), ß-lactamase-sensitive penicillins (J01CE) and ß-lactamase-resistant penicillins (J01CF). The broad-spectrum and newer antimicrobials, i.e. combinations of penicillins with ß-lactamase inhibitor (J01CR), cephalosporins (J01DA), carbapenems (J01DH) and fluoroquinolones (J01MA) contributed to 36% of the increase. Together, these amounted to 16% of total consumption in hospitals in Denmark in 1997, rising to 19% in 2001.
Conclusions: Although antimicrobial consumption in public hospitals in Denmark is low compared with other countries, the steady increase and change in pattern of their use are causes of concern, deserving close monitoring and further investigations.
Keywords: antibiotics, drug utilization, surveillance
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
To monitor the consumption and cost of medicinal products in Denmark, a national register of drug statistics was implemented in the early 1990s by the Danish Medicines Agency (Lægemiddelstyrelsen). On a monthly basis, community pharmacies report data on each prescription redeemed by patients, and hospital pharmacies report data on drugs dispensed to hospital wards.
Although 90% of antimicrobials are consumed in primary healthcare, there is evidence to suggest that antimicrobial selection pressure is much higher in hospitals.7 This, together with suboptimal infection-control practices, form the main reason for the high prevalence of antimicrobial resistance generally observed in hospitals.8 Therefore, monitoring antimicrobial consumption in hospitals is important in order to establish a relationship with the occurrence of resistance. Monitoring also reveals trends in prescribing practices in a country, and allows comparisons to be made between different hospitals and countries.6,9,10 This study was implemented to analyse antimicrobial consumption in public hospitals in Denmark during 19972001.
![]() |
Materials and methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Hospitals
All public hospitals in Denmark active during the study period were included in the analysis. Three hospitals that closed during this time, two in 1999 and one in 2000, were included. Hospitals that merged for functional or administrative reasons during the study period were treated as single groups for the entire period and their data were retrospectively merged. Psychiatric hospitals, rehabilitation centres as well as a neurological centre were excluded because of their particular patient recruitment. One small hospital did not consistently report antimicrobial data for the entire study period and was excluded. As at 2001, there were 55 hospitals or hospital groups included in the study. Data from inpatient wards as well as day patient wards were included. Data from psychiatric wards, emergency wards and outpatient clinics were excluded.
Antimicrobial data
Information on the antimicrobials used in hospitals in Denmark was obtained from the national register of drug statistics maintained by the Danish Medicines Agency.11 In this study, antimicrobials were defined as antibacterials for systemic use and are equivalent to group J01 of the Anatomical Therapeutic Chemical (ATC) classification system from the WHO Collaborating Centre for Drug Statistics Methodology.12 The group comprises the antimicrobial classes as listed in Table 1. For each hospital ward the Danish Medicines Agency provided data on consumption of each antimicrobial classas a number of defined daily doses (DDD)using the 2001 version of the ATC/DDD index.12 For each individual antimicrobial, the DDD is definedby the WHO Collaborating Centre for Drug Statistics Methodologyas the assumed average maintenance dose per day for a drug used for its main indication in an adult.13
|
As recommended by the WHO, the number of bed-days was chosen as the denominator.13,14 Bed-days denote the number of days each patient occupies a hospital bed. For each hospital such data were obtained from the National Board of Health (Sundhedsstyrelsen).1519
Data and statistical analysis
Data were processed and analysed using Microsoft Excel 2000, and SAS, Version 8.2. Hospital antimicrobial consumption was expressed as a number of DDD per 100 bed-days.13,14 Linear regression was used to determine the significance of the change in antimicrobial use in the observation period.
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
|
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
In Denmark, the observed increase in hospital antimicrobial use, expressed in DDD per 100 bed-days, was due to both an increase in the number of antimicrobial DDD (numerator) and a decrease in the number of hospital bed-days (denominator). This means that whereas the number of hospital bed-days decreased, hospitals in Denmark increased their consumption of antimicrobials. The decrease in the number of bed-days can be explained by the closing of several general and local hospitals. However, the proportion of bed-days originating from acute care referral hospitals, which are believed to admit the sickest patients, decreased slightly from 17.3% in 1997 to 16.7% in 2001, whereas the fraction of bed-days originating from teaching hospitals increased from 70.2% in 1997 to 70.5% in 2001. These minor changes in the structure of the hospital sector are unlikely to explain the observed large increase in antimicrobial use. During the same period, the average length of inpatient hospital stay decreased, from 5.8 days in 1997 to 5.2 days in 2001.15,19 This trend towards earlier discharge of patients led to a slight increase in hospital admissions despite a decreasing number of available hospital beds and could have contributed to the increase in antimicrobial prescribing. Firstly, whenever possible after a few days of parenteral therapy, patients who need antimicrobial treatment are now sent home with oral therapy provided by the hospital pharmacy. Secondly, the number of surgical procedures increased, from 888 117 in 1997 to 1 163 567 in 200123a 31% increase, which probably required increasingly greater quantities of antimicrobials for surgical prophylaxis. Thirdly, as a result of earlier discharge of the less sick patients, bed-days registered by hospitals may increasingly originate from sicker patients, who more often require antimicrobial treatment.
Finally, several recent articles in the Danish medical literature recommended combination antimicrobial therapy for initial empirical treatment of sepsis.2427 The observed increase in antimicrobial use could therefore be the consequence of the more frequent prescription of combination therapy to treat hospital patients. Unfortunately, antimicrobial-use data are only made available to the Danish Medicines Agency as aggregated data at ward level. Audits of prescription practices at patient level would be needed to verify this hypothesis.
In this study, we also demonstrated a shift from the so-called narrow-spectrum to the broad-spectrum and newer antimicrobials, although these still represented a small percentage of total use in hospitals in Denmark. A likely explanation is that Danish hospital doctors now practice a more defensive kind of medicine. Despite national and local guidelines for antimicrobial therapy,24 hospital doctors might be more prone to prescribe broad-spectrum antimicrobials for empirical treatment of bacterial infections. Additionally, they might increasingly be under pressure to produce speedy recoveries and less likely to step down therapy to narrow-spectrum antimicrobials when this becomes possible on the availability of microbiological results. With rare exceptions, such as ampicillin and sulphonamide resistance in Escherichia coli that lie between 30%50%, antimicrobial resistance in the microorganisms commonly isolated from clinical samples remains very low in Denmark and showed no significant increase during the study period.18 For example, resistance to cefuroxime, gentamicin and ciprofloxacin in Escherichia coli clinical isolates in Denmark is still <5%.18 Moreover, marketing of broad-spectrum and newer antimicrobials certainly plays a role in the change in pattern of antimicrobial use seen in Denmark.
Our study has a few limitations. Firstly, due to the progressive implementation of the data collection system from 1994 onwards, the original datasets on the number of DDD sometimes contained missing information on the wards' names. In this case, the DDD could only be assigned to the individual hospitals, but not at ward level. An unknown proportion of these DDD might have originated from use by outpatients, emergency or psychiatric patients. Such a bias, however, is believed to be small because these unassigned DDD only represented 11%13% of the total DDD used per year of the study period. Additionally, outpatients, emergency and psychiatric patients only represented a small percentage of patients in the identified wards and are believed to represent the same proportion in non-identified wards.
Secondly, data on antimicrobial use in private hospitals were not available; however, altogether these contribute very little to the hospital service in Denmark as there were only 13 small private hospitals in total representing 200 beds.28 Thirdly, we included use in paediatric wards but reported this use implementing the DDD that are only defined for adults by the WHO Collaborating Centre for Drug Statistics Methodology. This is, however, the only method to report total antimicrobial use from aggregated pharmacy data when it includes both adult and paediatric use.
In Denmark, hospital antimicrobial-use data represent an extremely useful source of information that is apparently not yet readily available in most other European countries, possibly because of the lack of centralized electronic data on the number of DDD and of reliable data on the number of occupied bed-days. Both the increase in total antimicrobial use and the shift towards broad-spectrum antimicrobials in hospitals in Denmark are causes of concern and deserve close surveillance and additional investigations. These national figures represent a first step towards a better understanding of antimicrobial use in hospitals in Denmark. Future efforts should be directed at analysing changes in individual hospitals and comparing levels and patterns of use between them. As a follow-up to this study, feedback reports are being prepared for each individual hospital to provide detailed information on the changes observed since 1997. These reports will be sent to the hospitals' microbiologists, who in Denmark are responsible for the hospital's antibiotic policy. It is expected that these individual reports will stimulate more detailed studies on local prescribing practices and help to set up interventions to improve antimicrobial prescribing in hospitals in Denmark.
![]() |
Acknowledgements |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
Footnotes |
---|
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
2 . Justesen, T., Korsager, B., Kolmos, H. R., et al. (2002). Vejledning i brug af antibiotika. In Lægeforeningens Medicinfortegnelse 2002/2003, 25.udgave, pp. 85680. Lægeforeningens forlag, Copenhagen, Denmark.
3 . Balslev, U., Benfield, T., Bremmelgaard, A. et al. (2001). Rationel anvedelse af antibiotika, 3. udgave. Klinisk Mikrobiologisk Afdeling 445, H:S Hvidovre Hospital, Hvidovre, Denmark. [Online.] http://www.hosp.dk/HHmikrobiologisk.nsf/ResponseDokumenter/2CF14A32B3507EEDC1256C2A002F242F (8 July 2004, date last accessed).
4 . Generel vejledning i antibiotikaterapi. (2002). Klinisk Mikrobiologisk Afdeling, Århus Universitetshospital,Århus, Denmark. [Online.] http://www.auh.dk/sks/afd/KlinMik/dk/ABvejled/ABVEJ_.AUH.pdf (8 July 2004, date last accessed).
5 . Cars, O., Mölstad, S. & Melander, A. (2001). Variation in antibiotic use in the European Union. Lancet 357, 18513.[CrossRef][ISI][Medline]
6 . Cars, O., Mölstad, S. & Melander, A. (2000). Large variation in antibiotic usages between European countries [abstract]. Clinical Microbiology and Infection 1, Suppl. 6, 216.
7 . Monnet, D. L., Sørensen, T. L. & Johansen, H. L. (2000). Comparison of the level of antimicrobial use in hospitals and in primary health care Denmark [abstract]. Infection Control and Hospital Epidemiology 21, 91.
8 . McGowan, J. E., Jr (1987). Is antimicrobial resistance in hospital microorganisms related to antibiotic use? Bulletin of the New York Academy of Medicine 63, 25368.[ISI][Medline]
9 . Krcmery, V., Grausova, S., Balin, O. et al. (1999). Decreased consumption of antimicrobial drugs after implementation of a new antibiotic policy in 1990. Journal of Hospital Infection 41, 757.[CrossRef][ISI][Medline]
10 . Monnet, D. L. & Sørensen, T. L. (1999). Interpreting the effectiveness of a national antibiotic policy and comparing antimicrobial use between countries. Journal of Hospital Infection 43, 23948.[CrossRef][ISI][Medline]
11 . Danish Medicines Agency. Forbrug af antibiotika. [Online.] http://www.laegemiddelstyrelsen.dk/1024/visLSArtikel.asp?artikelID=1437 (8 July 2004, date last accessed).
12 . WHO Collaborating Centre for Drug Statistics Methodology. (2001). ATC index with DDDs 2001. WHO Collaborating Centre for Drug Statistics Methodology, Oslo, Norway.
13 . WHO Collaborating Centre for Drug Statistics Methodology. (2001). Guidelines for ATC classification and DDD assignment. WHO Collaborating Centre for Drug Statistics Methodology, Oslo, Norway.
14 . Capellà, D. (1993). Descriptive tools and analysis. In Drug utilization studies. Methods and uses. (Dukes, M. N. G., Ed.), pp. 5578. WHO Regional Publications, European Series no. 45, Copenhagen, Denmark.
15 . Sundhedsstyrelsen. (1999). Virksomheden ved sygehus 1997. Munksgaards Forlag, Copenhagen, Denmark.
16 . Sundhedsstyrelsen. (2000). Virksomheden ved sygehus 1998. Schultz Information, Albertslund, Denmark.
17 . Sundhedsstyrelsen. (1999). Virksomheden ved sygehus 1999. Schultz Information, Albertslund, Denmark.
18 . Sundhedsstyrelsen. (2002). Virksomheden ved sygehus 2000, 2000. Schultz Information, Albertslund, Denmark.
19 . Sundhedsstyrelsen. (2003). Virksomheden ved sygehus 2001. Schultz Information, Albertslund, Denmark.
20 . DANMAP 2002. Use of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from food animals, foods and humans in Denmark. (2003). Danish Veterinary Institute, Copenhagen, Denmark. [Online.] http://www.dfvf.dk/Files/Filer/Zoonosecentret/Publikationer/Danmap/Danmap_2002.pdf (8 July 2004, date last accessed).
21 . Stichting Werkgroep Antibioticabeleid (SWAB). (2003). NETHMAP 2003 Consumption of antimicrobial agents and antimicrobial resistance among medically important bacteria in the Netherlands. [Online.] http://www.swab.nl/swab/swabfu.nsf/uploads/BBCDA0D2C7969870C1256D210030F9EC/$file/Nethmap2003.pdf (8 July 2004, date last accessed).
22 . European Surveillance of Antimicrobial Consumption. [Online.] http://www.ua.ac.be/ESAC (8 July 2004, date last accessed).
23 . Sundhedsstyrelsen. (2004). Landspatientregistret (National registry of patients), 1997-2001: Follow up statisticsSygdomsmønstret. Copenhagen, Denmark.
24 . Andersen, C. (1996). Kampen mod den blinde haglskudsterapi. Ugeskrift for Læger 158, 3012.
25 . Høiby, N., Tvede, M. & Dahl-Knudsen, J. (2001). Antibiotikavejledning i Lægeforeningens Medicinfortegnelse 2000. Ugeskrift for Læger 163, 1324.
26 . Kolmos, H. J. J. (1996). Rationel anvendelse af antibiotika på hospital. Ugeskrift for Læger 158, 2557.
27 . Pedersen, S. S. (2000). Empirisk antibiotisk behandling af sepsis. Ugeskrift for Læger 162, 28624.
28 . Amtsrådsforeningen. Alfabetisk oversigt over behandlingssteder. [Online.] http://www.sygehusvalg.dk/alfabetisk.aspx (8 July 2004, date last accessed).
|