Resistance to methicillin in isolates of Staphylococcus aureus from blood and cerebrospinal fluid in Wales, 1993–1997

Mari Morgana, Roland Salmonb, Dafydd Evans-Williamsa, Ian Hoseinc and D. Nicholas Lookerd

a Public Health Laboratory Service (Wales), University Hospital of Wales, Heath Park, Cardiff CF4 4XW b Public Health Laboratory Service Communicable Disease Surveillance Centre (Wales), Abton House, Wedal Road, Roath, Cardiff CF4 3QX c Cardiff PHL, University Hospital of Wales, Heath Park, Cardiff CF4 4XW d Rhyl PHL, Glan Clwyd District General Hospital, Rhyl LL18 5UJ, UK


    Abstract
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Surveillance data for organisms isolated from blood cultures and cerebrospinal fluid (CSF) specimens has been gathered electronically in Wales since 1993. Over this period the proportion of total reported organisms from blood cultures and CSF represented by methicillin-resistant staphylococci (MRSA) has risen steadily. This has corresponded to a rise in rates of methicillin resistance amongst Staphylococcus aureusisolated from blood cultures and CSF from 4 to 43%. In certain age/gender groups in 1997, more than 50% of isolates of S. aureus were resistant to methicillin, suggesting that a change in empirical treatment may be necessary for suspected staphylococcal sepsis.


    Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
The increase in numbers of isolates of Staphylococcus aureusresistant to methicillin (MRSA) has had a major impact on antibiotic prescribing practices and infection control policies in hospitals. Reporting of blood culture and cerebrospinal fluid (CSF) isolates to the Public Health Laboratory Service Communicable Disease Surveillance Centre (PHLS CDSC), showed that there was an increase in the proportion represented by MRSA in England and Wales, from 1.5% of all S. aureus isolates in 1989–1991 to 13.2% in 1995,1 and that 32% of S. aureus bloodstream infections in 1997 were caused by MRSA.2 In Wales, blood culture and CSF surveillance data have been gathered electronically since 1993. In addition, enhanced surveillance of all MRSA isolates from any site has been carried out since 1996. These two schemes have permitted changes in antibiotic resistance rates to be documented from 1993 to 1997.


    Materials and methods
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Surveillance is based on the results of routine microbiology testing in Wales, as reported to CDSC. Reports of isolates from blood cultures and CSF specimens and all new MRSA isolations are collected via CoSurv, a set of interconnected electronic database modules for communicable disease control.3 Data are transmitted to CDSC Wales for all-Wales analysis. Some under-reporting will have occurred over the surveillance period. The Mantel–Haenszel {chi}2 test was used for comparison of proportions, and trends were analysed using {chi}2 for trends. The Wilcoxon rank-sum test was used for the comparison of ages. Mid 1996 and 1997 population estimates4,5 were used as denominators for the calculation of rates for the total population surveyed.


    Results
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 Introduction
 Materials and methods
 Results
 Discussion
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The total number of organisms reported from blood cultures and CSF almost doubled (91% increase, 2059 to 3924) between 1993 and 1997 (Table I). The largest increase in the number of reports was between 1995 and 1996 (64%, 1996 to 3269), following a campaign to improve reporting to CDSC.


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Table I. Total blood culture and CSF specimens and S. aureus, MSSA and MRSA from blood culture and CSF specimens and their proportions of the total, reported in Wales via CoSurv 1993–1997 by specimen date
 
The number of reports of S. aureus from blood cultures and CSF increased by 138% (323 to 770) between 1993 and 1997. This increase represented a significant rise of S. aureus as a proportion of the total, from 16% (323/2059) in 1993 to 20% (770/3924) in 1997 ({chi}2 = 9.93, P>= 0.002). The number of reported methicillin-sensitive S. aureus (MSSA) rose by 45% between 1993 and 1997, but this represented a fall as a proportion of total organisms reported from 12.7% (252/2059) in 1993 to 9.7% (379/3924) in 1997 ({chi}2 = 18.70, P < 0.001). The number of MRSA reported, increased by 2555% (11 to 292), which represented a rise in the proportion of the total organisms identified as MRSA from 0.5% (11/2059) of the total in 1993 to 7.4% (292/3924) in 1997 {chi}2 = 197.91, P< 0.001). Overall this equated to a rise in rates of methicillin resistance in S. aureus isolated from blood cultures and CSF from 4.2% (11/263) in 1993 to 43.5% (292/671) in 1997 {chi}2 = 141.73, P < 0.001) (Table II).


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Table II. The number of S. aureus blood cultures and CSF by age group and gender and the percentage methicillin resistant reprted in Wales 1993–1997 by specimen date
 
Not all laboratories in Wales reported a high percentage of MRSA. The percentage resistant in 1997 ranged from a minimum of 0% to a maximum of 100%, although both laboratories reporting these extremes reported very small numbers. The median percentage reported was 37.5% and more than half the laboratories reported a resistance rate of>20%.

Comparison of patients with MRSA and MSSA isolated from blood cultures and CSF is shown in Table II. The highest rates of resistance to methicillin occurred in men aged 65 and over in 1997 (56.2% of isolates resistant to methicillin). Statistical analysis showed that MRSA was significantly more commonly associated with male gender (OR = 1.4 (1.11–1.75), P = 0.003) and that patients with MRSA were significantly older (mean age (95% CI): MSSA, 57.63 (56.35–58.91); MRSA, 65.78 (64.11–67.44); z = –6.54, P < 0.001).

Surveillance of all MRSA isolates in Wales from any clinical site in 1996 and 1997 showed that the reporting rate doubled (92.43/100 000 population in 1996; 177.76/100 000 in 1997). The proportion of isolates from blood culture and CSF specimens remained constant at 5.6% (1996, 152/2700; 1997, 292/5203).


    Discussion
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 Abstract
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 Materials and methods
 Results
 Discussion
 References
 
Since 1993, there has been an increase, both in absolute numbers and as a proportion of all isolates of S. aureus from blood and CSF. This can be attributed to the rising incidence of MRSA infections, since although the numbers of isolates of MSSA have increased, as a proportion of the total, the percentage has fallen. MRSA has both displaced MSSA as a causal organism and has been responsible for an excess number of infections.

It is possible that the higher numbers of MRSA reported from blood cultures and CSF in recent years occurred as a result of an increase in virulence of MRSA strains. This would cause more cases of serious illness, which would be reflected in the numbers reported from blood cultures and CSF specimens. The data from the total population surveillance do not support this hypothesis. Although the total number of blood cultures and CSF from which MRSA was isolated doubled between 1996 and 1997, the overall number of reports of MRSA from any site also doubled. The proportion of MRSA isolated from blood cultures and CSF, therefore, remained constant. The data indicate that a general increase in the incidence and prevalence of MRSA led in turn to more cases of serious illness attributable to both MRSA and all strains of S. aureus.

Data showed that the overall percentage of methicillin resistance in S. aureus from blood cultures and CSF in Wales in 1997 was 43%, but there was quite considerable variation between trusts. Combined data for England and Wales are only available up to 1995 for blood cultures and CSF, which showed the percentage of resistance to be 13%.1 Methicillin resistance of S. aureus in blood cultures and CSF in Wales in 1995 was 17%, higher than the national average. Examination of the England and Wales data for 1995 by region, showed that certain regions (particularly Thames regions) already had resistance rates of over 20%.1 It is not known whether resistance rates have continued to rise in these areas. Data on reported S. aureus bloodstream infections in England and Wales in 1997 showed that the proportion of methicillin resistance was 32% and that the spread was more evenly distributed across the country than reported previously.2 Only 13 isolates of S. aureus were reported from CSF in Wales between 1993 and 1997, with four reported in 1997, therefore data can be considered generally equivalent. It is possible that enhanced surveillance of MRSA in Wales from 1996 onwards has meant that laboratories in Wales are more likely to report an MRSA bacteraemia than an MSSA bacteraemia, resulting in an inflated rate of resistance compared with previous years and other regions.

Analysis of data in Wales by age and gender showed that, although there was variation in age- and gender-specific rates of methicillin resistance in S. aureus isolates from blood culture and CSF, the proportion of resistant strains was substantial in all groups with the exception of female patients under 15 years of age. The proportion of resistant strains in elderly men in 1997 was of particular concern. It may be that the empirical use of flucloxacillin or a cephalosporin6 is no longer appropriate in certain age/gender groups if serious staphylococcal sepsis is suspected. Since rates of methicillin resistance reported varies considerably between sites, analysis is required at a local level to determine the situation with regard to prescribing policies.


    Acknowledgments
 
Members of staff in the Microbiology Departments, Public Health Laboratories and Infection Control Teams in Wales are gratefully acknowledged for the provision of data. The project team is grateful for the support and guidance of the Welsh Hospital Infection Strategy Group and the Welsh Microbiology Standing Specialist Advisory Group.


    Notes
 
Correspondence address. CDSC (Wales), Abton House, Wedal Road, Roath, Cardiff CF4 3QX, UK. Tel: +44-1222-521-997; Fax: +44-1222-521-987; E-mail: mari.morgan{at}cdsc.wales.nhs.uk Back


    References
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
1 . Speller, D. C. E., Johnson, A. P., James, D., Marples, R. R., Charlett, A. & George, R. C. (1997). Resistance to methicillin and other antibiotics in isolates of Staphylococcus aureus from blood and cerebrospinal fluid, England and Wales, 1989–95. Lancet 350, 323–5.[ISI][Medline]

2 . Communicable Disease Report. (1998). Methicillin-resistant Staphylococcus aureus. Communicable Disease Report Weekly 8, 369–72.

3 . Henry, R. (1996). CoSurv: a regional computing strategy for communicable disease surveillance. PHLS Microbiology Digest 13, 26–8.

4 . Office of National Statistics. (1997). Office of National Statistics Monitor PP1 97/1.

5 . Office of National Statistics. (1998). Office of National Statistics Monitor PP1 98/1.

6 . Joint Formulary Committee (1998). British National Formulary 35, 235.

Received 11 October 1998; returned 12 April 1999; revised 22 April 1999; accepted 24 May 1999