1 Public Health Laboratory Service, Communicable Disease Surveillance Centre (Wales), Abton House, Wedal Road, Cardiff CF14 3QX; 2 Department of Medical Microbiology and Public Health Laboratory, University Hospital of Wales, Cardiff CF14 4XW, UK
Received 17 October 2002; returned 4 December 2002; revised 13 December 2002; accepted 3 February 2003
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Abstract |
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Keywords: fusidic acid resistance, Staphylococcus aureus, fusidic acid prescribing
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Introduction |
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Materials and methods |
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Results |
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Discussion |
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Correlational studies are limited by their inability to link exposure with disease in individuals or to control for the effects of potentially confounding factors. For example, it is not possible to determine whether one patient was responsible for most isolates or prescriptions. Including repeat isolates has previously been shown to have a negligible effect on the estimate of resistance rates in urinary isolates in community settings.4,6 Sampling bias could result in the observed association if there were systematic differences in specimen-taking behaviour between high- and low-prescribing practices. The MSSA isolates were from samples taken in the community and are less likely than hospital isolates to be subjected to potential bias from variation in screening practices for MRSA.
Published studies on the selection of fusidic acid resistance following topical treatment consist mainly of uncontrolled studies. This is inadequate for differentiating between the alternative hypothesis that increasing resistance is the result of clonal spread within an at-risk population.7 Four patients (4/17, 24%) in a case series derived from all fusidic acid-resistant S. aureus isolates at the Middlesex Hospital bacteriology department in 1971 had previously received topical fusidic acid.8 Twenty-four patients (24/55, 44%) in a consecutive cases series of fusidic acid-resistant S. aureus isolates at the microbiology department of Harrogate District Hospital in 1998 had used topical fusidic acid in the previous 6 months.9 A trial that detected no resistance to fusidic acid in 1010 cases of skin sepsis treated with sodium fusidate ointment is frequently cited as evidence against the selection of resistance; however, all the patients in this trial also received other systemic antibiotics.10
The only published controlled study compared fusidic acid resistance in nasal isolates of S. aureus in 204 patients treated with topical fusidic acid in the previous 815 months in primary care with 204 controls matched for age, sex and general practitioner.11 Resistance was identified in 1 of the 74 S. aureus isolates in the treated group and none of the 70 isolates in the control group. This study did not have sufficient power to detect any effect of topical fusidic acid on resistance. If resistant organisms are selected in 0.5% of individuals who are exposed to topical fusidic acid a cohort study would require 2000 in each group to have a power of 80% to detect a relative risk of 50 at the 5% significance level.
Systemic fusidic acid is an important treatment for uncommon but serious infection, in particular osteomyelitis or endocarditis caused by penicillin-resistant staphylococci. Our data support the urgent need for high quality epidemiological studies to determine whether the observed increase in resistance is causally associated with the increased use of topical fusidic acid.
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Acknowledgements |
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Footnotes |
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References |
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2
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Brown, E. M. & Wise, R. (2002). Fusidic acid should be used with restraint. British Medical Journal 324, 1394.
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4
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Howard, A. J., Magee, J. T., Fitzgerald, K. A. & Dunstan, F. D. J. (2001). Factors associated with antibiotic resistance in coliform organisms from community urinary tract infection in Wales. Journal of Antimicrobial Chemotherapy 47, 30513.
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