1 MEMO, Department of Clinical Pharmacology, Ninewells Hospital, University of Dundee, Dundee DD1 9SY; 2 General Practitioner, Red Wing, Wallacetown Health Centre, Dundee; 3 Department of Geography and Geosciences, University of St Andrews, St Andrews; 4 Division of Environmental and Applied Biology, School of Life Sciences, University of Dundee; 5 Department of Molecular and Cellular Pathology, University of Dundee, Dundee, UK
Received 14 January 2002; returned 20 June 2002; revised 15 August 2002; accepted 28 August 2002
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
Materials and methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Study population
The study population comprised individuals from the Tayside region of Scotland who were resident in Tayside and registered with a general practitioner between January 1993 and December 1995. Urine sample data were obtained from the Department of Medical Microbiology at Ninewells Hospital, which has a catchment population of 163 000 people.
Study subjects
The study included two analyses, a cohort study using all children born in Tayside in 1993 and measuring exposure to antibacterials in the 2 years following birth, and a casecontrol study comparing children who submitted a urine sample with the general population. Cases were children from Tayside aged 010 years who submitted urine samples or dip slides for culture and susceptibility to the Ninewells laboratory between January 1993 and December 1995. Each case was agesex matched to two comparators from the general population who had not submitted urine samples.
The relationship between age and prevalence of trimethoprim resistance in Gram-negative bacteria from urinary samples was measured in samples submitted from subjects aged 040 and resident in Tayside from 1993 to 1995.
Definition of risk factors
Exposure to dispensed drugs or hospitalization. Subjects were defined as exposed to an antibacterial drug if they were dispensed any antibacterials listed in the British National Formulary (BNF) in sections 5.1.1 to 5.1.13 before the date of submission of the urine sample. Exposure to hospital admission was ascertained from the Scottish Morbidity Record for all acute hospitals in Tayside.
Socio-economic deprivation. Socio-economic status of the subjects was determined by small area postcodes derived from census data and analysed as Carstairs deprivation categories.2 Socio-economic deprivation was defined as being in category 6 or 7.
Statistical analysis
KaplanMeier statistics for the cohort study and odds ratios for the casecontrol study were calculated with SAS version 8 (SAS Institute Inc., Cary, NC, USA).
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Children who submitted urine samples were different from the general population of children aged 010 years (Table 1). They were more likely to be socio-economically deprived (OR 3.77; 95% CI 3.394.20), to have been exposed to antibacterials (OR 1.88; CI 1.702.07) or to have been hospitalized (OR 1.78; 95% CI 1.621.97).
|
|
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
We found that children from socio-economically deprived areas were exposed to antibacterials earlier than children from less deprived areas, whereas two previous studies reported that children from affluent areas were more likely to be exposed to antibacterials than children from deprived areas.5,6 However, both of these studies measured total exposure (e.g. number of prescriptions per 1000 inhabitants) rather than time to first exposure. Socio-economic deprivation is consistently associated with respiratory illness in general and particularly with acute respiratory infections, such as otitis media. Potential explanations include overcrowding,7 higher passive exposure to smoking8 and lower levels of breast-feeding.9 The fact that socio-economic class does influence exposure to antibacterials is a further reason for believing that epidemiological studies of resistance in urinary isolates may be biased or confounded, because in our study children who submitted urine samples were significantly more likely to be deprived than the general population.
There are limited data in the literature concerning the relationship between age and antibacterial resistance. Studies of the faecal microflora show high rates of resistance in children under the age of 10 but we have only identified one study that analysed resistance in 01 year olds.10 This showed that resistance was lower in <1 year olds than in 15 year olds, but was higher in 15 year olds than in 617 year olds. These data suggest that the complex relationship between age and resistance in urinary isolates from our patients (Figure 1) is likely to reflect changes in the faecal microflora. However, our results also show that children who submit urine samples differ from the general population (Table 1) and it would be preferable to undertake further studies on the faecal microflora of a more representative sample of the general population. It is plausible that the relationship between age and resistance in cross-sectional studies reflects changes in individuals over time. If so, this is probably due to intensive exposure to antibacterials in the first 2 years of life with a subsequent decline in resistance due to lower use of antibacterials by older children. This possibility could only be confirmed by a longitudinal study.
![]() |
Acknowledgements |
---|
![]() |
Footnotes |
---|
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
2
.
Steinke, D. T., Seaton, R. A., Phillips, G., MacDonald, T. M. & Davey, P. G. (2001). Prior trimethoprim use and trimethoprim-resistant urinary tract infection: a nested casecontrol study with multivariate analysis for other risk factors. Journal of Antimicrobial Chemotherapy 47, 7817.
3 . Thrane, N., Olesen, C., Md, J. T., Sondergaard, C., Schonheyder, H. C. & Sorensen, H. T. (2001). Influence of day care attendance on the use of systemic antibiotics in 0- to 2-year-old children. Pediatrics 107, E76.[Medline]
4 . Bergus, G. R., Levy, S. M., Kirchner, H. L., Warren, J. J. & Levy, B. T. (2001). A prospective study of antibiotic use and associated infections in young children. Paediatric and Perinatal Epidemiology 15, 617.[ISI][Medline]
5 . Henricson, K., Melander, E., Molstad, S., Ranstam, J., Hanson, B. S., Rametsteiner, G. et al. (1998). Intra-urban variation of antibiotic utilization in children: influence of socio-economic factors. European Journal of Clinical Pharmacology 54, 6537.[ISI][Medline]
6
.
Hofmann, J., Cetron, M., Farley, M. M., Baughman, W. S., Facklam, R. R., Elliot, A. J. et al. (1995). The prevalence of drug-resistant Streptococcus pneumoniae in Atlanta. New England Journal of Medicine 333, 4816.
7
.
Rees Jones, I., Urwin, G., Feldman, R. A. & Banatvala, N. (1997). Social deprivation and bacterial meningitis in North East Thames region: three year study using small area statistics. British Medical Journal 314, 7945.
8 . Spitzer, W. O., Lawrence, T., Dales, R., Hill, G., Archer, M. C., Clark, P. et al. (1990). Links between passive smoking and disease: a best-evidence synthesis. Clinical Investigative Medicine 13, 1742.
9 . Howie, P. W., Forsyth, J. S., Ogston, S. A., Clark, A. & Florey, C. D. (1990). Protective effect of breast feeding against infection. British Medical Journal 300, 116.[ISI][Medline]
10 . Degener, J. E., Smit, A. C., Michel, M. F., Valkenburg, H. A. & Muller, L. (1983). Faecal carriage of aerobic Gram-negative bacilli and drug resistance of Escherichia coli in different age-groups in Dutch urban communities. Journal of Medical Microbiology 16, 13945.[Abstract]