Health Technology Assessment 2003; Vol 7: number 39
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Systematic review of isolation policies in the hospital
management of methicillin-resistant Staphylococcus
aureus: a review of the literature with epidemiological and economic
1 Academic Department of Geriatric Medicine, Royal Free Campus, Royal Free and
University College Medical School, University of London, UK
2 University Department of Medical Microbiology, Royal Free Campus, Royal Free
and University College Medical School, University of London, UK
3 Laboratory of HealthCare Associated Infection, Health Protection Agency,
4 Health Services Research Unit, Department Public Health and Policy, London School of
Hygiene Tropical Medicine, University of London, UK
5 Ecology and Epidemiology, Department of Biological Sciences, University of
Warwick, Coventry, UK
6 Division of Healthcare-Associated Infection and Antimicrobial Resistance,
Health Protection Agency, Communicable Disease Surveillance Centre, London, UK
7 University Library, Royal Free Campus, Royal Free and University College
Medical School, University of London, UK
8 Department of Social Medicine, Bristol University Medical School, University of
* Corresponding author
The incidence of patient infection and
colonisation with methicillin-resistant Staphylococcus aureus (MRSA) continues to rise in UK hospitals and poses a considerable socio-economic burden. Management of this problem includes screening to detect
asymptomatic carriers and the use of various isolation measures to control its
spread. There has been much debate about the rationale and cost-effectiveness
of these measures. MRSA guidelines have been published but there was an urgent
need for a systematic review to examine the evidence base for these
- To review the evidence for the
effectiveness of different isolation policies and screening practices in
reducing the incidence of MRSA colonisation and infection in hospital
- To develop transmission models to study
the effectiveness and cost-effectiveness of isolation policies in controlling
- The search strategy
covered the main subject areas addressed in the review: MRSA; screening;
patient isolation; and outbreak control.
- Studies with
economic data or analysis were included.
- Searches of electronic databases MEDLINE (19662000), EMBASE (19802000), CINAHL
(19822000), The Cochrane Library (2000) and SIGLE (19802000).
- Manual searches of the principal hospital infection journals to validate electronic database searches.
- No language restrictions were imposed.
- Abstracts were appraised by two or three reviewers
working together and selected if they mentioned endemic or epidemic MRSA and an
attempt at control in a hospital setting.
- Two investigators reviewed the full papers independently and
extracted data where studies were prospective, employed planned comparisons
using retrospective data or used isolation wards or nurse cohorting (designated
nurses for the care of MRSA-affected patients).
The study period was divided into phases,
where appropriate, and the following data were extracted:
- details of all populations under investigation
- details of patient
isolation, screening and other infection control measures (e.g. eradication of
carriage, antibiotic restriction, hand-hygiene, feedback, ward closures)
- information on
outcomes (e.g. infection, colonisation, bacteraemia, death)
- details of potential
confounders or effect modifiers including length of stay, antibiotic use,
strain change, pre-existing trends, numbers colonised on admission, seasonal
effects, staffing levels and aspects of study design that might introduce
Authors were written to when isolation or screening policies, or their timing, were unclear.
Studies were excluded if isolation policies
or timing of interventions remained unclear, or if the only outcomes reported
were colonisations and screening policy was unclear or changed substantially.
- Data were summarised
in table form. Formal meta-analysis was considered inappropriate owing to
heterogeneity in study design and patient populations.
- The strength of
evidence in each study was evaluated by examining the study design, quality of
data, size of effect and presence of plausible alternative explanations due to
confounders and biases.
- Stochastic and
deterministic compartmental models were used to investigate the long-term
transmission dynamics of MRSA.
- Hospital and community
populations were considered, but all transmission was assumed to occur in
- Models studied the
impact of a fixed-capacity isolation ward.
- Local cost data were
coupled to models to produce economic evaluations.
- Models were also
used to address issues of statistical validity in publication and analysis
Results: systematic review
- There were 4382
abstracts from which 254 full-article appraisals were made. Forty-six were
included in the final review.
- one prospective cohort cross-over study
- two prospective cohort studies with historical controls
- nine prospective interrupted time series (ITS) (three had prospective data collection but unplanned interventions)
- six prospective observational one-phase studies
- five hybrid retrospective/prospective ITS
- one retrospective cohort study with
systematic data collection and the comparison decided on in advance of
examining the data
- two retrospective studies with the
comparison decided on before examination of the data
- eighteen retrospective ITS
- two retrospective observational studies.
- Eighteen studies
described the use of isolation wards. Study durations ranged from 3 months
to 15 years, and involved between 11 and 5345 MRSA cases.
- Nine studies described the use of nurse
cohorting (NC). Study durations ranged from 3.5 months to 4 years, and involved between 5 and 1074 MRSA cases.
- Nineteen studies described other isolation
policies. Study durations ranged from 1 month to 9 years, and involved between 9 and 1771 cases.
- In nearly all the
studies isolation was combined with at least one other simultaneous
- Twenty-five studies
were set in one or more entire hospitals, 20 were set in individual hospital
units and one used survey data from multiple hospitals.
Quality of studies
- There were few
formally planned prospective studies with predefined pre- and postintervention
assessment and adjustment for potential confounders was lacking.
- Regression to the
mean effects and confounders were plausible threats to the validity of many
studies. The predominance of unplanned retrospective reports suggests that
reporting bias may be important.
- Statistical analysis was absent or inappropriate in all but two studies.
- There was no robust economic evaluation.
- No conclusions could
be drawn about the effect of isolation in one-third of studies. In studies with
multiple simultaneous interventions it was not possible to assess the relative
contribution of individual measures.
- Most others provided
evidence consistent with reduction of MRSA. In half of these, the evidence was
considered weak because of poor design, major confounders and/or risk of
- Two studies presented evidence consistent with immediate isolation reducing transmission.
- Stronger evidence
was presented in the larger and longer time series, with large changes in MRSA
numbers, detailed information on interventions and relative absence of
plausible alternative explanations.
- There were six such studies:
||Three presented conflicting evidence of the effectiveness of isolation wards (with other measures) in reducing MRSA infection hospital wide: one
reduced infection, one did not and one resulted in control for many years until
a change in strain and/or an increase in the number of patients colonised on
admission overwhelmed the institution.
||One presented evidence that single-room
isolation with screening, eradication and an
extensive hand-hygiene programme reduced MRSA infection and colonisation
||One provided evidence that NC in single rooms with screening and eradication reduced infection
hospital wide. One paediatric intensive care unit study provided evidence that single-room isolation and patient cohorting in bays (with screening, feedback of infection rates and hand-hygiene education) reduced infection.
- It was not possible
to draw any conclusions about the cost-effectiveness of the interventions
because of the poor quality of the economic evaluative work presented. The
costs included were not comprehensive many items were omitted and they were
not consistent as the items included in the studies varied widely.
- Equilibrium endemic
prevalences of MRSA in hospitals with fixed-capacity isolation facilities were
shown to be dependent on the detection rate of MRSA patients, the number of
isolation beds available and the transmissibility of the organism.
- Improving either
the detection rate or isolation capacity was shown to decrease endemic levels
provided that the other was not the limiting factor.
- The final endemic
level often depended on when the isolation ward opened, with ultimate
eradication often possible only when the isolation ward was opened early.
- In many scenarios,
long-term control failure occurred owing to saturation of isolation facilities
as the numbers colonised on admission rose. However, even when such control
failure occurred, the isolation ward delayed the rate at which prevalence
increased and reduced the ultimate endemic level. Saturation of isolation
facilities can be prevented by ensuring sufficient capacity.
- A paucity of
reliable information on key parameter values hampered economic evaluations.
However, under a wide range of plausible parameter values estimated
independently, substantial savings could be achieved over 10 years compared
with a policy of no isolation, provided that the burden of unused isolation
ward capacity and staff time was not too great. Assumptions were made about the
unused capacity on the isolation wards that had implications for the estimates
of opportunity costs. Our assumptions possibly overestimated the opportunity
costs. The opportunity costs in practice may have been less and would depend
crucially upon what the alternative uses would have been and what would have
been the cost of maintaining unused capacity. We lacked data to estimate these
Implications for healthcare
- There was evidence
that intensive concerted interventions that include isolation can substantially
reduce MRSA, even in settings with a high level of endemic MRSA. Little
evidence was found to suggest that current isolation measures recommended in
the UK are ineffective, and these should continue to be applied until further
research establishes otherwise.
- Future research
should concentrate on prospective planned comparisons, with predefined pre- and
postintervention periods and systematic assessment and adjustment for potential
confounders as necessary. Randomised controlled trials with cluster randomisation
by hospital or specialist unit are one possibility. Consideration should also
be given to other valid designs, including those based on prospective
interrupted time series as, although they represent weaker designs, they may
often be more feasible.
- Priority research
questions include an examination of the effect of adequately sized isolation
wards in hospitals with endemic MRSA; the effects of single-room isolation with
an extensive hand-hygiene programme, screening and eradication; and NC, with
screening and eradication. Study designs that permit the identification of the
effects of both individual interventions and the effects of combined
interventions should be considered.
- Attention should be
paid in intervention studies to estimating the resources used in the
intervention in a comprehensive way. Cost vectors can then be applied that are
designed as far as possible to reflect the opportunity costs associated with
the use of these resources.
- We recommend that
future outbreak reports and intervention studies be written up in a
standardised manner with full recording of interventions, outcomes and
confounders to ensure that specific threats to validity are addressed. We have
produced guidelines to facilitate this.
- An audit system that
enables infection control teams to collect and use data on potential effect
modifiers, alongside current MRSA surveillance systems, needs to be designed,
piloted and evaluated. Evaluation should focus on the role of the system in
planning interventions and interpreting their outcomes.
Cooper BS, Stone SP, Kibbler CC, Cookson
BD, Roberts JA, Medley GF, et al.
Systematic review of isolation policies in the hospital management of methicillin-resistant
Staphylococcus aureus: a review of
the literature with epidemiological and economic modelling. Health Technol Assess 2003;7(39).
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