Resistance to methicillin in isolates of Staphylococcus aureus from blood and cerebrospinal fluid in Wales, 19931997
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
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Abstract
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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.
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Introduction
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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 19891991 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.
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Materials and methods
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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
MantelHaenszel
2 test was used for comparison of proportions, and
trends were analysed using
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.
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Results
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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 19931997 by specimen date
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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
(
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 (
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
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
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 19931997 by specimen date
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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
(1.111.75), P = 0.003) and that patients with MRSA were
significantly older (mean age (95% CI): MSSA, 57.63 (56.3558.91); MRSA, 65.78
(64.1167.44); 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).
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Discussion
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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.
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Acknowledgments
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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.
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Notes
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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 
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References
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2
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Communicable Disease Report. (1998).
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3
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Henry, R. (1996). CoSurv: a regional
computing strategy for communicable disease surveillance. PHLS Microbiology
Digest 13, 268.
4
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Office of National Statistics. (1997). Office of
National Statistics Monitor PP1 97/1.
5
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Office of National Statistics. (1998). Office of
National Statistics Monitor PP1 98/1.
6
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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