1 Antibiotic Resistance Monitoring & Reference Laboratory, Specialist & Reference Microbiology Division; 2 Statistics Unit and 3 Communicable Disease Surveillance Centre, Health Protection Agency, 61 Colindale Avenue, London NW9 5HT; 4 British Society for Antimicrobial Chemotherapy, 11 The Wharf, 16 Bridge Street, Birmingham B1 2JS, UK
Received 30 July 2003; returned 15 September 2003; revised 22 September 2003; accepted 23 September 2003
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Abstract |
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Methods: Routine susceptibility data for bacteraemia isolates were collected from over 90% of hospitals in England.
Results: During 19952001, the prevalence of ciprofloxacin resistance trebled, from 2.1% to 6.5%. Isolates from men were more frequently resistant than those from women, possibly because infections in men more often involve nosocomial strains. Resistance was rare (<1.5%) in isolates from patients aged <1 year; among older patients, resistance was unrelated to age in isolates from women, but peaked in the 1544 age group for men.
Conclusions: The prevalence of ciprofloxacin resistance in E. coli from bacteraemia is strongly associated with sex and, to a lesser extent, age.
Keywords: E. coli, bacteraemia, gender, ciprofloxacin resistance
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Introduction |
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Materials and methods |
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Voluntary reporting to the Health Protection Agencys LabBase/CoSurv surveillance system captures routine microbiological information on bacteraemias from over 90% of the clinical diagnostic laboratories in England and Wales.3 Analysis for Staphylococcus aureus, where there is a parallel mandatory reporting scheme, suggests that about two-thirds of bacteraemias are reported.4
Data analysis
All reports of E. coli bacteraemia in England, received under the routine reporting scheme during 19952001, were extracted for analysis. Overall trends were described either as a ratio of the proportions resistant in two specific years (a risk ratio, RR), or as an average percentage increase between successive years, estimated by a generalized linear model of the binomial family and a log link function. Significance tests were based on logistic regression, and so compared odds ratios. The overall trend was estimated by controlling for Region, sex and age; sex-specific trends were estimated controlling for Region and age; differences between age groups were tested controlling for Region and year; Region-specific trends were estimated controlling for sex and age group.
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Results |
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Discussion |
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It was striking also, from this analysis, that although more E. coli bacteraemias occur in women, ciprofloxacin resistance is more prevalent in those from men. We are unaware of any such strong association between resistance and gender having been found previously. A likely factor is that women are anatomically more prone than men to ascending urinary tract infections by the resident gut microflora, with some of these infections leading to bacteraemias. Because such infections are rarer in men (at least until later life, when prostatitis has an impact), relatively more of the fewer E. coli bacteraemias in men are likely to be caused by hospital strains, which may tend to be more resistant than E. coli from the normal gut flora.
This hypothesis is supported by the observations, using the same database, that resistance was more prevalent in E. coli isolates from men to gentamicin (RR, 1.30; 95% CI: 1.141.50) and ceftazidime (RR, 1.64; 95% CI: 1.342.02), both of which are used almost exclusively in hospitals. Conversely, the pattern was reversed for ampicillin (RR, 0.95; 95% CI: 0.930.97) and trimethoprim (RR, 0.88; 95% CI: 0.850.92), which are oral drugs widely used in the community. Selection in women may also be mitigated by a disinclination to use quinolones in those of child-bearing age.
Routine laboratory data received by the Health Protection Agency offer few insights into the origins of the reported bacteraemias. The British Society for Antimicrobial Chemotherapys Bacteraemia Surveillance (http://www.bsacsurv.org) does have such data, based on 10 consecutive E. coli bacteraemias and isolates per annum from each of 25 UK and Irish hospitals. Among 482 E. coli isolates in 2001 and 2002, 279 (58%) were from women; and 67% of those from women were community-acquired (<48 h hospitalization) compared with 60% of those from men (P = 0.14). Ciprofloxacin resistance was seen in 7.4% (22/296) of the community-acquired isolates compared with 8.4% (14/166) of those from hospital-acquired infections (P = 0.72). These differences failed to achieve statistical significance but are consistent with the hypothesis that E. coli bacteraemias in men are more likely to be nosocomial, and to be caused by ciprofloxacin-resistant organisms. This hypothesis is further supported by an analysis of 861 E. coli bacteraemia episodes treated at a London hospital during 19691987.5 Among hospital-acquired bacteraemias, the male:female ratio was 1.2:1, compared with 0.46:1 among community-acquired cases. Resistances to gentamicin and (in that earlier period) ampicillin were more frequent among the nosocomial cases. The study pre-dated ciprofloxacin, and the resistance rates were not analysed in relation to gender.
The relationship between the patients age and the prevalence of resistance also was notable (Table 2). Very low resistance rates in those aged <1 year might reflect the lack of fluoroquinolone use in these infants. Since, however, quinolone use should also be limited in the 114 year group (where these drugs are only used if their benefits are thought to exceed the arthropathy risks) the relationship is more likely to reflect the fact that neonatal units develop a particular flora that contributes to patient colonization.6
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Acknowledgements |
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Footnotes |
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References |
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2 . Livermore, D. M., James, D., Reacher, M. H. et al. (2002). Trends in fluoroquinolone (ciprofloxacin) resistance in Enterobacteriaceae from bacteremias in England and Wales, 19901999. Emerging Infectious Diseases 8, 4738.[ISI][Medline]
3
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Reacher, M. H., Shah, A., Livermore, D. M. et al. (2000). Bacteraemia and antibiotic resistance of its pathogens reported in England and Wales between 1990 and 1998: trend analysis. British Medical Journal 320, 2136.
4 . Public Health Laboratory Service. (2003). Staphylococcus aureus bacteraemia: England, Wales and Northern Ireland. Communicable Disease Report CDR Weekly 13, 510.
5 . Gransden, W. R., Eykyn, S. J., Phillips, I. et al. (1990). Bacteremia due to Escherichia coli: a study of 861 episodes. Reviews of Infectious Diseases 12, 100818.[ISI][Medline]
6 . Fryklund, B., Tullus, K., Berglund, B. et al. (1992). Importance of the environment and the faecal flora of infants, nursing staff and parents as sources of gram-negative bacteria colonizing newborns in three neonatal wards. Infection 20, 2537.[ISI][Medline]