a Maasland Ziekenhuis, Department of Clinical Pharmacy and Toxicology, PO Box 5500, 6130 MB Sittard; b University Hospital Nijmegen, The Netherlands and c Aberdeen Royal Hospitals, Aberdeen, UK
Abstract
The use of antibiotics in Dutch hospitals between 1991 and 1996 was investigated. A total of 54 hospitals responded to the enquiry, representing over 70% of all hospital beds in The Netherlands. The use of antibiotics in Dutch hospitals, expressed as defined daily doses (DDD) per hundred bed days, gradually increased from 37.2 DDD per 100 bed days in 1991 to 42.5 DDD per 100 bed days in 1996. The antibiotic that showed the largest increase in use was co-amoxiclav. Its use increased more than three-fold from 3.93 DDD per 100 bed days in 1991 to 12.5 DDD per 100 bed days in 1996. The increase in use of co-amoxiclav exceeded the increase in total antibiotic consumption. The use of cephalosporins remained fairly constant during the study period, but there were changes in the relative use of the different cephalosporin groups. The use of earlier cephalosporins gradually decreased, whereas the use of the more recently developed cephalosporins increased between 1991 and 1996. Ciprofloxacin and norfloxacin were the most commonly used fluoroquinolones throughout the study period. The use of ofloxacin increased significantly between 1991 and 1996, approaching the levels of use of ciprofloxacin and norfloxacin. There may be complex reasons for the increases, which need further analysis, but they mirror those few data available from elsewhere in the world. Possible explanations include more intensive treatment to expedite patient discharges, sicker patients with more serious infections and more resistant organisms.
Introduction
The worldwide increase in resistance to antibiotics is of great concern. It is accepted that there is a relationship between resistance and the use of antibiotics, but it is only by understanding patterns of use that future strategies for the deployment of antibiotics and control of resistance can be planned. Only very limited recent data on the use of antibiotics in various countries are available. The present study describes the use of antibiotics in Dutch hospitals for the period 1991 to 1996.
Materials and methods
Data on the use of antimicrobial agents in Dutch hospitals between 1991 and 1996 were collected by means of a questionnaire distributed to all Dutch hospital pharmacists. The use of antimicrobial agents was expressed as the number of defined daily doses (DDD) per 100 bed days for systemic antibacterial agents. The number of admissions and the number of days spent in hospital were recorded for each hospital for each year. The number of bed days was obtained by subtracting the number of admissions from the total number of days spent in hospital. This provides a more realistic picture of the actual number of patients present in the hospital, as the day of admission and the day of discharge are both included in the length of stay whereas the patient is only present (and consuming drugs) for a part of both days. The length of hospital stay was obtained by dividing the total number of days spent in hospital by the number of admissions. Statistical analysis of the data was performed by Student's t-test.
Results
A total of 54 hospitals responded to the enquiry. This sample represented over 70% of all Dutch hospital beds. Not all hospitals were able to provide complete data between 1991 and 1996. Of the 54 respondents 21 were able to do so. Of the participating hospitals, four were university hospitals, 25 were teaching hospitals, with more than 500 beds and 25 were hospitals with fewer than 500 beds. The mean length of hospital stay decreased gradually from 10.5 days in 1991 to 9.2 days in 1996 (P < 0.001) as is shown in Table I.
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The use of aminoglycosides remained fairly constant during the study period (Figure 3). Of these, gentamicin was by far the most commonly used aminoglycoside, and its use increased during the study period (0.82 DDD per 100 bed days in 1991 to 1.22 DDD per 100 bed days in 1996). Tobramycin was used at an almost constant level of 0.34 DDD per 100 bed days between 1991 and 1995, but the use in 1996 was higher (0.48 DDD per 100 bed days). The use of netilmicin gradually decreased from 0.35 DDD per 100 bed days in 1991 to 0.14 DDD per 100 bed days in 1996. The use of amikacin never exceeded 0.01 DDD per 100 bed days.
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The use of fluoroquinolones is shown in Figure 5. Ciprofloxacin and norfloxacin were the most commonly used fluoroquinolones in all years. The use of ofloxacin increased significantly between 1991 and 1996, approaching that of ciprofloxacin and norfloxacin. The use of pefloxacin fell from 0.26 DDD per 100 bed days in 1991 to 0 between 1994 and 1996.
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This study was one of the first undertaken by the newly founded European Society of Chemotherapy and Infectious Diseases (ESCMID) working party, the European Study Group on Antibiotic Policies (ESGAP), which was founded to promote rational use of antimicrobial drugs throughout Europe. DDD methodology is the best available method of comparing the use of drugs in hospitals in different countries. A DDD is assigned to each drug by the World Health Organization. Although only one value for a DDD is given, often very different doses are used in practice (e.g. 375 mg amoxycillin bid orally for urinary tract infections to 2 g six times daily for meningitis and a DDD of 1 g). But, nonetheless, expressing the use of antibiotics in DDD per 100 bed days, enables realistic comparisons of antibiotic use in hospitals in different countries to be made.3,4 Some studies have used other, more clinically relevant, figures for antibiotic use, such as the DDA (defined daily administration).5 This methodology critically assesses the actual daily dosages used. However, DDA values are country specific, which precludes direct intercountry comparison of the data.
The data presented in Table II were derived from all hospitals which provided data from at least 1 year. Data from hospitals providing figures for all 6 years were also analysed separately. The results of this analysis were almost identical to those presented in Table II
and therefore only the overall data are discussed and presented in Table II
.
The use of antibiotics in Dutch hospitals gradually increased from 37.2 DDD per 100 bed days in 1991 to 42.5 DDD per 100 bed days in 1996. The use of antibiotics in 1991 was higher than the use in the preceding year, 1990. In that year the mean use of antibiotics in Dutch hospitals was 34.1 DDD per 100 bed days.6
There appears to be a relationship between increased antibiotic consumption in Dutch hospitals and the decreased duration of hospital stay, a decrease of more than 10% from 10.5 to 9.22 days during the study period being observed. This may indicate shorter bed stays for more acutely ill patients. The Dutch duration of hospital stay is similar to that of French hospitals (mean duration of hospital stay in 1993 was 10.5 days), shorter than that in Germany (11.9 days), Italy (13.2 days) or Spain (11.7 days), but longer than that in the UK (7.7 days).7
The most striking increase was observed in the use of co-amoxiclav. Its consumption increased proportionately more than the overall consumption of antibiotics. This can, at least partly, be explained by the increasing use of this drug in surgical prophylaxis. In a study of Dutch antibiotic formularies undertaken in 1994, co-amoxiclav was recommended more frequently in newer formularies than in older ones.1,2 Replacement of amoxycillin by co-amoxiclav for respiratory tract infections also contributed to the increased use of co-amoxiclav. This increased use of co-amoxiclav has been described in other countries.8 As the use in surgical prophylaxis is always of short duration (mostly one single 2.2 g dose), the number of patients who have been treated with co-amoxiclav probably increased even more than the increase expressed in DDDs suggests. This information is not available.
The overall use of cephalosporins showed a minor increase in the study period, but a marked increase was observed in the use of cefotaxime, ceftazidime and ceftriaxone. Again, this trend is being observed elsewhere8 because of various factors, such as use for surgical prophylaxis and as treatment for pneumonia.
A significant increase was found in the use of fluoroquinolones, explained by an increase in the use of ofloxacin. The use of the other fluoroquinolones, such as norfloxacin and ciprofloxacin showed only minor increases.
In 1990, the use of antibiotics in 20 Dutch hospitals was lower than that in 30 Belgian and 20 German hospitals. The overall use was 34.1 DDD per 100 bed days in Dutch hospitals, 37.9 in German hospitals and 55.6 in Belgian hospitals.6 In 1990, the use of fluoroquinolones and co-amoxiclav was much lower in Dutch hospitals when compared with those in Belgium. This study has revealed a considerable increase in the use of these agents. This was also observed in Belgian hospitals between 1991 and 1993.5 Other antibiotics which showed an increased use were cefotaxime, ceftazidime, ceftriaxone, carbapenems and glycopeptides, whereas the use of ampicillin and amoxycillin declined. This trend was similar to that observed in the present study. The relative use of penicillins is much higher in Dutch hospitals than in Belgian hospitals (57% of total DDD/100 bed days in Dutch hospitals versus 24% of DDA/100 bed days in Belgium). The same study found that the relative use of cephalosporins and fluoroquinolones was much higher in Belgian hospitals. Data on absolute use could not be compared because the Belgian data were presented in DDA/100 bed days.5 Such data showing widespread differences in prescribing between adjacent countries, with similar patient demographics and infectious diseases are fascinating and more detailed analysis is likely to yield important data on how prescribing can be improved. However, more detailed quality-of-use data is needed. In the absence of computerized prescribing, the collection of such data is very time consuming, but might include: the clinical indication for an antibiotic, microbiological data (including differences in resistance patterns), actual dosing schedules and routes of administration.
Very limited further data are readily available from other countries. In a Finnish university hospital, a mean use of 50 DDD per 100 bed days was found in 1989.9 A high use of antibiotics was also noted in 1987 for hospitals in Italy: 58 DDD per 100 bed days (range 33.860.5), Spain: 83.5 DDD per 100 bed days (range 57.4109.5) and Portugal: 89.7 DDD per 100 bed days (range 38.8149.2).10
This study has important limitations, as it only describes the actual consumption of antibiotics, without specifying the infections for which these were used. It is, however, of great importance to gain insight into the actual consumption of antibiotics in hospitals as this contributes to the observed increased prevalence of multiresistant strains of bacteria. The European Study Group on Antibiotic Policies (ESGAP), wishes to collect data on antimicrobial drug use in hospitals throughout Europe, in order to obtain insight into the relative use of drugs and changing patterns of antibiotic drug prescription. Those who are interested in participating in the collection of these data are kindly invited to contact Drs Janknegt or Gould for further information.
Notes
* Corresponding author. Tel: +31-46-4597709; Fax: +31-46-4597971; E-mail: rjanknegt{at}capitolonline.nl
References
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Received 4 May 1999; returned 28 July 1999; revised 17 August 1999; accepted 29 September 1999