Conceived and designed the experiments: GH MB DMB. Analyzed the data: GH MB DG. Wrote the paper: GH MB ML DG DMB. Principal investigator: MB. Supported the principal investigators and contributed to the manuscript: ML. Provided IT support and contributed to the manuscript: DG. Contributed to the study design: DMB. Critically reviewed all manuscript drafts and provided information on the clinical aspects of MRSA detection methods: DMB. Contributed to the supervision of this study: MJMB MP.
This study was financially supported by Becton Dickinson (San Diego, CA) and 3M (Minneapolis, MI), through research grants without publication restrictions. This did not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. GAAH and DMG are financially supported by BaseCase (Berlin, Germany). In their capacities as consultants for BaseCase software, GAAH and DMG have performed consulting work for Becton Dickinson. This did not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. DB, MJP, and JML declare no competing interests.
Screening at hospital admission for carriage of methicillin-resistant
A simulation model of MRSA transmission was used to determine costs and effects over 15 years from a US healthcare perspective. We compared admission screening together with isolation of identified carriers against a baseline policy without screening or isolation. Strategies included selective screening of high risk patients or universal admission screening, with PCR-based or chromogenic media-based tests, in medium (5%) or high nosocomial prevalence (15%) settings. The costs of screening and isolation per averted MRSA infection were lowest using selective chromogenic-based screening in high and medium prevalence settings, at $4,100 and $10,300, respectively. Replacing the chromogenic-based test with a PCR-based test costs $13,000 and $36,200 per additional infection averted, and subsequent extension to universal screening with PCR would cost $131,000 and $232,700 per additional infection averted, in high and medium prevalence settings respectively. Assuming $17,645 benefit per infection averted, the most cost-saving strategies in high and medium prevalence settings were selective screening with PCR and selective screening with chromogenic, respectively.
Admission screening costs $4,100–$21,200 per infection averted, depending on strategy and setting. Including financial benefits from averted infections, screening could well be cost saving.
The low nosocomial prevalence in Scandinavian countries and the Netherlands has been
ascribed to stringent policies to control the spread of MRSA. Bootsma et al. have
investigated the contribution of different components of the Dutch
Several detection tests are now commercially available, each with different test characteristics and costs. The impact and relative importance of a test's sensitivity, specificity and test delay depend on the screening strategy used and the MRSA prevalence in the catchment population. Here, we used a modeling approach to assist hospital administrators in informed decision making on the implementation of an admission screening strategy.
The objectives were (1) to estimate the costs of screening and isolation per infection averted for various admission screening strategies, (2) to compare two MRSA detection tests within these strategies and (3) to investigate the relative importance of test sensitivity, specificity and test delay. Our analysis focused on the United States.
We performed an analysis of costs and effects of universal and selective MRSA
screening at hospital admission, combined with isolation of identified MRSA
carriers, over a timeframe of 15 years, using a 3% annual discount rate
We used a previously published
Below, we present a brief overview of the model, a more detailed account is available
elsewhere
MRSA transmission occurs primarily via patient-to-patient transmission mediated by
the hands of health care workers (HCWs). The adherence of HCWs to the hand-washing
protocol is assumed to be constant over time. Transmission is 20 times more likely
to occur within a given hospital unit, compared to transmission between units.
Transmission can also occur via HCWs who are colonized in the nose/throat
We used an average daily probability of developing an infection of 0.59% for a
hospitalized carrier
At baseline there is neither active screening for MRSA nor isolation of identified or suspected carriers. The nosocomial prevalence remained at a steady state of 15% over the entire time frame in high prevalence settings. As a baseline for the medium prevalence setting, we assumed a steady-state prevalence of 5% over the time frame, although without interventions the prevalence would continue to rise to the high prevalence level.
We evaluated ‘Selective’ screening of ‘high risk’ patients
and ‘flagged’ patients only, as well as ‘Universal’
screening of all patients. Both strategies were evaluated with a PCR-based test and
a chromogenic media-based test (see
Test | Sensitivity |
Specificity |
Test delay (days) |
PCR | 92.5 | 97.0 | 0.5 |
Chromogenic |
|||
At 24 h | 78.3 | 98.6 | 1.5 |
At 48 h | 87.6 | 94.7 | 2.5 |
1 The chromogenic media-based test is evaluated after 24 and 48 hours of incubation. Patients with positive results are isolated at both time points, with the last result after 48 hours being considered final.
To simulate a regionally implemented MRSA screening policy, all three hospitals in
the model are assumed to implement identical screening strategies at the same time.
The chromogenic media-based test is evaluated after 24 and 48 hours of incubation.
Patients with positive results are isolated at both time points, with the last
result after 48 hours being considered final. Pre-emptive isolation, defined as
isolation upon readmission for the duration of the test delay until confirmed
negative for carriage of MRSA, is limited to ‘flagged’ patients only.
Single room isolation is assumed to reduce the risk of transmission by 80%
We additionally investigate four alternatives to our base-case assumptions: (1) full pre-emptive isolation, that includes pre-emptive isolation for ‘high risk’ as well as ‘flagged’ patients; (2) the absence of pre-emptive isolation; (3) only 1 out of the 3 hospitals in the model implements screening; (4) screening with a chromogenic media-based test, using only the results after 24 h of incubation.
The total investment cost borne by the hospital is assumed to consist of the
additional cost of isolation plus the cost of screening. The screening and isolation
costs were calculated by multiplying estimated resource use (including labor) by
unit prices (
Item | Units | Costs ($) |
Take swab by nurse |
5 (min) | 3.1 |
Clinical risk assessment by nurse |
5 (min) | 3.1 |
Transport swab | 1 | 0.35 |
PCR - test cost per sample | 1 | 24.0 |
PCR - test clinical lab. technician time per sample
|
1.5 (min) | 0.76 |
Fixed screening costs | 6.55 | |
PCR - annual cost real-time PCR equipment |
1 | 4,315 |
Chromogenic - test cost per sample | 1 | 3.5 |
Chromogenic - clinical lab. technician time per sample
|
11.1 (min) | 5.6 |
Fixed screening costs | 6.55 | |
Contact precautions materials per day |
12 | 12.4 |
Contact precautions additional nurse time per day |
36 (min) | 22.3 |
Contact precautions additional physician time per day
|
10 (min) | 13.7 |
Cleaning of room |
30 (min) | 7.4 |
1 The time required to estimate the risk of being a carrier was based on factors such as hospital admission within last 12 months or transfer from another healthcare facility (only in case of selective screening).
2 Annual cost based on Smartcycler (Cepheid, Sunnyvale, CA), straight line depreciation using an interest rate of 4%, a cost of $35,000, a lifetime of 10 years and a resale value of 20%.
3 Total $1.04, including gloves ($0.057), gown ($0.46), mask ($0.27), hair cap ($0.049), disinfectant 75 mL ($0.20) required for each of 12 entries into an isolation room per day.
4 Additional cleaning costs are only incurred in case of a positive finding.
Labor costs are based on nationwide average hourly wages for registered
nurses ($29.8), physicians ($66.3), clinical laboratory
technologists and technicians ($24.4) and janitors and cleaners
($11.9). (source: bureau of labor statistics, US department of
labor). A 24.3% administration overhead was applied to all labor
costs
In a one-way sensitivity analysis we investigated the impact of alternately varying the test sensitivity (50–100%), specificity (50–100%) and test delay (0–5 days), on the costs and infections averted. Additionally, we investigated the impact of varying key model parameters on the aCER. The sensitivity analysis was conducted using the strategy selective screening with PCR in a high prevalence setting.
Relative to baseline, all strategies reduced MRSA prevalence in the first years
of screening, yielding prevalence rates below 1% after 15 years (
The upper graph shows the impact of the screening strategies on the nosocomial prevalence over time. The lower graph shows the percentage of total patients in isolation over time for each strategy. Both graphs show the mean of 1000 runs of the model.
Percentages of patients in isolation over time are characterized by a peak at the
start of the screening program (
The annual undiscounted cost in US$ (2007) of strategies ‘Selective PCR’ (left) and ‘Selective Chromogenic’ (right) in a high prevalence setting. The first two years represent baseline (no screening and no isolation).
Strategy | Test | Screening ($m) | Isolation($m) | Total Investment Cost ($m) | Cases of infection | Cases of infection averted vs. baseline | aCER (Total investment cost $ per infection averted) (95% UI) | Isolation |
Peak isolation capacity required (%) |
Patients screened | Time to 50% prevalence reduction (Yrs) |
Prevalence after 15 years (%) |
Baseline | None | 0 | 0 | 0 | 2753 | 0 | NA | 0 | 0 | 0 | NA | 15 |
Selective | PCR | 6.17 | 4.05 | 10.22 | 547 | 2,206 | 4,633 (4,477–4,843) | 83,774 | 6.2 | 200,179 | 3.46 | 0.28 |
Selective | Chromogenic | 2.87 | 5.78 | 8.65 | 668 | 2,085 | 4,149 (3,948–4,442) | 119,407 | 7.2 | 200,839 | 3.92 | 0.49 |
Universal | PCR | 10.42 | 5.89 | 16.30 | 501 | 2,252 | 7,237 (7,000–7,487) | 121,681 | 7.8 | 375,725 | 3.33 | 0.22 |
Universal | Chromogenic | 4.21 | 8.15 | 12.36 | 622 | 2,131 | 5,799 (5,484–6,142) | 168,449 | 9.1 | 375,739 | 3.73 | 0.42 |
Baseline | None | 0 | 0 | 0 | 918 | 0 | NA | 0 | 0 | 0 | NA | 5 |
Selective | PCR | 5.81 | 2.71 | 8.52 | 237 | 681 | 12,508 (11,454–13,677) | 55,981 | 2.9 | 188,374 | 4.19 | 0.20 |
Selective | Chromogenic | 2.69 | 3.69 | 6.38 | 296 | 622 | 10,257 (9,110–11,819) | 76,226 | 3.3 | 188,461 | 4.96 | 0.33 |
Universal | PCR | 10.42 | 4.61 | 15.03 | 209 | 709 | 21,195 (19,841–23,347) | 95,310 | 4.3 | 375,745 | 3.87 | 0.17 |
Universal | Chromogenic | 4.21 | 6.18 | 10.39 | 271 | 647 | 16,056 (14,593–18,106) | 127,664 | 5.0 | 375,766 | 4.58 | 0.27 |
1 The number of patient days in isolation.
2 The peak isolation capacity required by the hospital in 97.5% of all simulations.
3 The number of years required to reach a 50% reduction in the nosocomial prevalence.
The cumulative and discounted costs in US$ (2007) and discounted effects for one hospital over 15 years, using base-case assumptions, for a high (15%) as well as a medium (5%) prevalence setting.
The total number of infections at baseline - over the 15 year timeframe -
amounted to 2,753 and 918 for high and medium prevalence, respectively. Of these
infections, the number averted by the different screening and isolation
strategies ranged from 2,085 to 2,252 and from 622 to 709 for high and medium
prevalence, respectively (
The least costly strategy in terms of the costs per infection averted is
‘Selective Chromogenic’. The investment costs of this strategy in a
high prevalence setting are $8.7 m and it averts a total of 2,085
(2,085/2,753 = 76%) infections compared to baseline
(
The most effective strategy was ‘Universal PCR’, averting 2,252 (82%) and 709 (77%) infections in high and medium prevalence settings, respectively. This strategy was also the most costly, requiring a total investment of $16.3 m and $15.0 m for high and medium prevalence, respectively.
To visualize comparisons between strategies, we plotted costs and health gains of
each strategy (
The investment costs in millions in US$ (2007) are depicted on the
horizontal axis and health benefits (infections averted) on the vertical
axis. The points shown represent the infections averted and investment
costs of each screening strategy. The origin represents baseline, a
policy of neither screening nor isolation. The incremental ratios of D
effectiveness to costs are represented by the slopes of the lines
connecting these points. The decreasing slope illustrates the
diminishing return on investment when extending the selective PCR to
universal screening in both settings. The strategy ‘Universal
Chromogenic’ is dominated by ‘Selective PCR’ (higher
costs, less health benefits), and is therefore not considered a relevant
option. The incremental investment costs, infections averted and
incremental cost-effectiveness ratio between selected strategies are
shown in the table beneath the graphs.
In the medium prevalence setting, the aCER - compared to baseline – of screening ‘high risk’ patients with a chromogenic based test (‘Selective Chromogenic’) is $10,300 per infection averted. Substituting the chromogenic media-based test by a PCR-based test (‘Selective PCR’), represented by line B, costs an incremental $2.1 m and averts an incremental 59 infections, resulting in an iCER of ‘Selective PCR’ compared to ‘Selective Chromogenic’, of $36,200 per additional infection averted. The incremental returns on investment strongly diminish with an extension of ‘Selective PCR’ to all patients (‘Universal PCR’), at an iCER of $232,700 per additional infection averted (line C).
Universal screening with a chromogenic media-based test is dominated in both settings by selective screening with PCR (i.e. selective screening with PCR is both cheaper and more effective).
Comparing selective screening with PCR using base-case assumptions with the
individual scenarios (
Strategy | Test | Screening ($m) | Isolation($m) | Total Investment Cost ($m) | Cases of infection | Cases of infection averted vs. baseline | aCER (Total investment cost $ per infection averted) (95% UI) | Isolation |
Peak isolation capacity required (%) |
Patients screened | Time to 50% prevalence reduction (Yrs) |
Prevalence after 15 years (%) |
Baseline | None | 0 | 0 | 0 | 2753 | 0 | NA | 0 | 0 | 0 | NA | 15 |
PCR | 6.17 | 4.05 | 10.22 | 547 | 2,206 | 4,633 (4,477–4,843) | 83,774 | 6.2 | 200,179 | 3.46 | 0.28 | |
PCR | 6.17 | 7.63 | 13.80 | 512 | 2,241 | 6,158 (5,920–6,406) | 157,568 | 8.3 | 200,176 | 3.37 | 0.22 | |
PCR | 6.17 | 3.62 | 9.79 | 579 | 2,174 | 4,502 (4,298–4,703) | 74,714 | 5.5 | 200,178 | 3.58 | 0.37 | |
PCR | 6.24 | 4.79 | 11.02 | 801 | 1,952 | 5,646 (5,232–6,086) | 98,900 | 5.8 | 202,360 | 3.50 | 2.59 | |
Chromo-genic 24 | 2.87 | 3.70 | 6.58 | 758 | 1,995 | 3,299 (3,076–3,555) | 76,543 | 5.9 | 200,730 | 4.23 | 0.80 |
1 The number of patient days in isolation.
2 The peak percentage of total patients in isolation in 97.5% of all simulations.
3 The number of years required to reach a 50% reduction in the nosocomial prevalence.
The cumulative and discounted costs in US$ (2007) and discounted effects for one hospital over 15 years, for a high (15%) prevalence setting.
The investment costs and the infections averted of varying test sensitivity and
specificity from 50% to 100% with increments of 5%, are
shown in
The costs of selective PCR-based screening are depicted on the horizontal axis and health benefits (infections averted) on the vertical axis. The left graph shows the combined results of alternately varying the test’s sensitivity and specificity from 50% to 100%, with increments of 5%. The right graph shows the test delay varied from 0 to 5 days, with increments of 0.5 day, for different pre-emptive isolation strategies: No pre-emptive isolation (diamonds), pre-emptive isolation of ‘flagged’ patients only, i.e. the base-case scenario (squares), and full pre-emptive isolation, i.e. ‘flagged’ patients as well as ‘high risk’ patients (triangles).
Parameters are ranked by the magnitude of their impact on the average cost-effectiveness ratio (aCER), of selective screening with PCR (aCER: $4,600) under base-case assumptions (base-case parameter values are shown between brackets).
The true costs attributable to MRSA infection are unknown and the appropriate
method to determine these costs is debated
Investment costs, savings (based on $17,645 averted hospital costs
per averted infection (
Our scenario analysis confirms that admission screening will be less effective
and more costly if neighboring hospitals do not screen
When extending the time frame, the costs per infection averted decrease (
Our results contrast with another recent economic analysis
The outcomes from our study depend on the validity of the transmission model. To assess the validity of our model we conducted extensive sensitivity analyses and have provided estimates around our estimated aCER. We did not perform a full probabilistic sensitivity analysis to estimate the impact of the uncertainty in the assumed model parameter values, because the computation time required would be unfeasibly long for the type of model we used. Instead, the impact of varying model parameters was investigated using one-way sensitivity analysis.
Because a model remains a simplification of real life situations, the inherent
limitations should be discussed. No limit was set on isolation capacity and it
was assumed that all identified carriers were isolated, with corresponding
isolation costs. However, this ideal policy will not always be realized
There are no published estimates on the additional cost (if any) of a patient in
a single room versus a semi-private room or a ward
As our main outcome measure was investment costs per infection averted, our
calculations neglect the benefit of patients of not having MRSA. The healthcare
utilization costs of treating MRSA infection are driven by the patient’s
length of stay. The length of stay varies considerably across hospitals and even
between wards in a single hospital. For hospitals with a relatively short length
of stay, the screening strategies investigated in this study will result in
lower cost savings and lower net benefits than shown in
For a more comprehensive determination of cost-effectiveness from the societal
perspective, more data is needed on the value of averted infections in terms of
the additional survival, quality of life and the costs of MRSA infection, during
hospital stay as well as after discharge. One would also hope to include the
potential negative effects of isolation on quality of care
Based upon our simulation model, three important conclusions can be drawn related to MRSA admission screening:
(1) Excluding any financial benefits from averted infections, the choice of strategy depends on the setting, the costs of isolation and the hospital’s willingness to pay to avert infection. In both settings, selective screening with a chromogenic media-based test is the least costly strategy in terms of the cost per infection averted. More infections can be averted by replacing the chromogenic media-based test with a PCR test, at additional costs. The additional infections that can be averted with universal screening with PCR are relatively costly.
(2) The ranking of strategies is sensitive to additional daily costs of single room isolation. At thresholds of $45 and $106, in high and medium prevalence settings respectively, selective screening with PCR becomes dominant over selective chromogenic media-based screening.
(3) Assuming $17,645 benefit per infection averted, all evaluated strategies using base-case assumptions are cost-saving with the exception of universal screening with PCR in a medium prevalence setting. The most cost-saving strategies in high and medium prevalence settings are selective screening with PCR and selective screening with a chromogenic media based test, respectively.