Although a model based analysis indicated that a strategy of universal topical decolonisation, regardless of MRSA status, was optimal in the short term, such untargeted use may select for resistance, making such strategies unsustainable in the long term.44 45
For this reason, restricting the use of topical agents to patients known to be positive for MRSA may be preferred. Excluding pre-emptive decolonisation of all patients, the optimal strategy was targeted decolonisation based on the outcomes of universal admission and weekly screens using polymerase chain reaction. The next best strategy was admission and weekly screening of all patients using chromogenic agar with decolonisation of those found to be MRSA positive (fig 2), although this had a much lower probability (compared with polymerase chain reaction) of being optimal at a 5% prevalence on admission.
Where decolonisation strategies are not used, admission and weekly screening coupled with isolation using contact precautions potentially reduces MRSA transmission, infections, and deaths. Use of polymerase chain reaction in this case, however, led to only modest reductions in MRSA infection rates compared with culture. This is a consequence of a small number of patients with unusually long lengths of stay accounting for a disproportionate number of MRSA related bed days.38
Although screening using polymerase chain reaction reduces the number of unisolated bed days while MRSA positive compared with culture, the percentage reduction will be small for patients with long stays.
Among strategies without decolonisation, universal polymerase chain reaction screening was unlikely to be cost effective within the usual NHS range of £20
000 to £30
000 per QALY gained, with chromogenic agar based screening and strategies targeting high risk patients being favoured. This reflects the lack of effect on progression from colonisation with MRSA to infection, and large uncertainty about the effect of contact precautions in reducing transmission, with a possibility that such precautions increase transmission.30
This could plausibly occur as a result of poorer compliance with hand hygiene associated with glove use.46
Strengths and weaknesses of the study
Strengths of the modelling approach adopted here include the use of a dynamic transmission model to take into account that preventing MRSA acquisition in one patient benefits both that patient and other patients through reduced risk of cross infection.47 48 49
Such knock-on effects are important in high transmission settings such as intensive care units, and static decision analytical models would fail to take these effects into account.50 51 52
Accurate modelling of the length of stay distribution is also critical for assessing the benefits of rapid screening, as is accurately quantifying additional length of stay and mortality attributable to MRSA infections.38
These are likely to have been substantially over-estimated in the past by models that ignore the dynamic nature of infection.53
Additionally, quantifying what is often substantial uncertainty in parameter values and accounting for it in strategy evaluations represents a more rational approach than one based only on point estimates for parameter values.
Limitations relate to simplifying assumptions and generalisability. Because the model ignores infections after discharge and because colonisation with MRSA may have longer term health consequences, as well as potentially leading to readmissions of colonised patients, the results presented are expected to underestimate health benefits and cost savings resulting from interventions to control MRSA.
For targeted strategies we used a decolonisation regimen of mupirocin alone, whereas many protocols may use skin antiseptics concurrently. As the best available evidence on effectiveness was for mupirocin alone, however, we used these to inform our model. Our estimates of the effectiveness of decolonisation are therefore likely to be conservative.
Pre-emptive universal decolonisation with agents such as chlorhexidine may reduce other healthcare associated infections, particularly catheter related ones, the benefit of which was not incorporated into our models.54 55 56 57
Conversely, decolonisation using nasal mupirocin has been reported to be associated with an increase of infections caused by other micro-organisms, although it remains unclear whether the link is causal.32
Therefore, with the possible exception of mupirocin based decolonisation interventions, cost effectiveness estimates reported here are likely to be conservative: true net monetary benefits are likely to be somewhat higher than those we report. Another assumption is lack of resistance to topical antimicrobial agents used for decontamination of colonised patients. This will not be the case for all settings; mupirocin resistance is not uncommon and there has been a recent report of an MRSA strain with a reduced susceptibility to chlorhexidine,44
the clinical relevance of which is still open to debate.58 59
In view of this, in all evaluations of decolonisation regimens we have carried out a secondary analysis excluding universal use of decolonisation.
Comparison with other studies
A Health Technology Assessment of the cost effectiveness of MRSA screening in Scotland concluded that screening of all admissions to hospital using chromogenic agar with isolation of those identified as potential carriers proved most effective at reducing prevalence and most cost effective compared with no screening, and screening according to risk (of unit) and clinical risk assessment, regardless of whether such screening used agar, chromogenic agar, or polymerase chain reaction.60
A further study61
projected that universal screening for MRSA could result in an important reduction in MRSA rates over three to five years, and while chromogenic agar and polymerase chain reaction had a comparable effect, polymerase chain reaction was more costly.
Our study differed in that we limited the focus to intensive care units and we evaluated a wide range of intervention policies accounting for parameter uncertainty. We combined available evidence to determine distributions for parameters describing the effectiveness of interventions.
Implications and future research
Since 2006 the emphasis on the prevention and control of healthcare associated infections, particularly MRSA, has increased and this research sits in a context of wide ranging national guidance on infection control.62 63
Although infection prevention methods of patient isolation and decolonisation (or suppression) are recommended, decisions remain locally driven and dependent on risk analysis. As a result, practices vary substantially between NHS trusts. While universal MRSA screening has been mandatory in England and Wales since December 2010, considerable uncertainty remains about the cost effectiveness of this and accompanying interventions. This study highlights the importance of evaluating the cost effectiveness of recommended prevention strategies and is especially important in supporting appropriate decision making during a period of cost restraint.
Our research found that even with conservative assumptions for the benefits of interventions, decolonisation strategies were highly likely to be cost effective in an intensive care unit setting and that, when combined with decolonisation, universal screening was likely to be a cost effective option. However, we highlight the need to be vigilant for the development of resistance to agents used for decolonisation. In contrast, we found no evidence to support universal screening (with any technology) as a cost effective intervention when accompanied by isolation. This reflects the lack of evidence on the effectiveness of contact precautions in substantially reducing transmission. Given this uncertainty, we found that isolation and screening strategies targeted to high risk patients were likely to be a more efficient use of resources.
The need for clinical investigations into the effectiveness of interventions has been further highlighted through this research.61 64
The large extent of uncertainty about parameters reflects the scarcity of high quality research, and some important model parameters can only be estimated using single studies. Methodologically rigorous assessments from randomised trials of the effectiveness of interventions in reducing MRSA transmission and infections are rare. Considering a recent study,65
where large reductions (62%) in MRSA infections were achieved using universal screening without accompanying decolonisation (among other interventions), rigorous evaluation of isolation should be a priority. Such studies would be of great value in helping to make better decisions about intervention policies.
Future work should also extend the model to describe long term patterns of patients’ movements (between and within the hospital and community) and to account for the spread of resistance to topical antimicrobial agents. An increase in resistance in MRSA strains has the potential to greatly reduce the efficacy of decolonisation and therefore may severely compromise these strategies. Understanding the longer term consequences of widespread decolonisation, whether pre-emptive or targeted, and devising strategies to minimise the risks of emerging resistance should be a priority.
What is already known on this topic
- Meticillin resistant Staphylococcus aureus (MRSA) continues to cause a high burden of disease in intensive care units (ICUs)
- Many ICUs use MRSA screening combined with isolation or decolonisation in an attempt to reduce MRSA infections, but practices vary widely between units
- New screening technologies allow MRSA carriage to be detected more rapidly and with greater sensitivity, although at greater cost than conventional approaches
What this study adds
- Screening and decolonisation are potentially cost saving in ICUs if MRSA is sensitive to decolonising agents
- Universal polymerase chain reaction based screening accompanied by decolonisation is likely to represent an efficient use of resources
- Targeting screening and isolation to high risk groups is likely to be a more efficient use of resources than universal screening with isolation or universal pre-emptive isolation