MRSA colonisation (eradicating colonisation in people without active invasive infection)

Abstract

Introduction

Methicillin-resistant Staphylococcus aureus (MRSA) contains a gene that makes it resistant to methicillin as well as to other beta-lactam antibiotics, including flucloxacillin, cephalosporins, and carbapenems. MRSA can be part of the normal body flora (colonisation), especially in the nose, but it can cause infection. Until recently, MRSA has primarily been a problem associated with exposure to the healthcare system, especially in people with prolonged hospital admissions or underlying disease, or after antibiotic use. In many countries worldwide, a preponderance of S aureus bloodstream isolates are resistant to methicillin.

Methods and outcomes

We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of treatment for MRSA nasal or extra-nasal colonisation in adults? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2014 (BMJ Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview).

Results

At this update, searching of electronic databases retrieved 850 studies. After deduplication and removal of conference abstracts, 356 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 273 studies, and the further review of 83 full publications. Of the 83 full articles evaluated, no studies were added at this update. We performed a GRADE evaluation for three PICO combinations.

Conclusions

In this systematic overview, we categorised the efficacy for five interventions based on information about the effectiveness and safety of antiseptic body washes, chlorhexidine-neomycin nasal cream, mupirocin nasal ointment, systemic antimicrobials, and other topical antimicrobials.

Key Points

Methicillin-resistant Staphylococcus aureus (MRSA) has a gene that makes it resistant to methicillin as well as other beta-lactam antibiotics, including flucloxacillin, cephalosporins, and carbapenems, which limit the number of treatment options for infection.

MRSA can be part of the normal body flora (colonisation), especially in the nose, but it can cause infection, especially in people with prolonged hospital admissions or underlying disease, or after antibiotic use.

MRSA carriers are at increased risk for recurrent MRSA infection.

MRSA carriers who are found to be colonised with MRSA at multiple body sites or who are found to be persistently colonised with MRSA over time are at greater risk of infection with that bacterium.

Trauma, wounds, surgical incisions, or use of indwelling medical devices can facilitate the introduction of MRSA, which colonises the skin and mucosa into deeper tissues, leading to MRSA infection.

MRSA is now a leading cause of community-associated skin and soft tissue infections.

Bloodstream infection due to MRSA is an all-too-common problem worldwide.

We have searched for evidence from RCTs and systematic reviews of RCTs on eradication of colonised MRSA in adults in hospitals and residential homes, outpatients, and healthcare workers.

Mupirocin nasal ointment may reduce or eradicate MRSA colonisation compared with placebo, and may be as effective as topical fusidic acid plus oral trimethoprim-sulfamethoxazole (co-trimoxazole), although studies have given conflicting results.

• We don't know whether antiseptic body washes, chlorhexidine–neomycin nasal cream, systemic antimicrobials, or other topical antimicrobials are effective at clearing MRSA colonisation.

Clinical context

General background

Methicillin-resistant Staphylococcus aureus (MRSA) carriers are at increased risk for recurrent MRSA infection. Carriers who are found to be colonised with MRSA at multiple body sites or who are found to be persistently colonised with MRSA over time are at greater risk of infection with that bacterium. Furthermore, trauma, surgical incisions, or use of indwelling medical devices in the MRSA carrier may facilitate the introduction of the organism into deeper tissues, leading to MRSA infection.

Focus of the review

It has been thought that reduction or elimination of MRSA colonisation might lead to reductions in MRSA infection rates. Different topical and systemic antimicrobial regimens have been tried in various patient populations, with variable outcomes. Given that MRSA infection remains a significant problem in healthcare settings and, now, in the community, it is important to re-examine the evidence for or against the treatment of MRSA-colonised patients.

Comments on evidence

We found RCT evidence for three of our five interventions of interest. No direct information from RCTs was found for chlorhexidine-neomycin nasal cream or other topical antimicrobials. The included studies may have limitations to their generalisability for a variety of reasons including: the use of co-interventions, inclusion of patients with MSSA, or small number of comparators.

Search and appraisal summary

The update literature search for this overview was carried out from the date of the last search, January 2010, to June 2014. For more information on the electronic databases searched and criteria applied during assessment of studies for potential relevance to the overview, please see the Methods section. Searching of electronic databases retrieved 850 studies. After deduplication and removal of conference abstracts, 356 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 273 studies and the further review of 83 full publications. Of the 83 full articles evaluated, no studies were added at this update.

About this condition

Definition

Methicillin-resistant Staphylococcus aureus (MRSA) is an organism resistant to methicillin by means of the mecA gene. This confers resistance to the majority of beta-lactam antibiotics, including flucloxacillin, oxacillin, cephalosporins, and carbapenems. Antimicrobial resistance is defined as the failure of the antimicrobial to reach a concentration in the infected tissue high enough to inhibit the growth of the infecting organism. MRSA presents in the same way as susceptible S aureus. It can be part of the normal flora (colonisation), or it can cause infection. The phenomena of colonisation and infection should be treated as separate entities. In many countries worldwide, a preponderance of S aureus bloodstream isolates are resistant to methicillin. MRSA colonisation growth of MRSA from a body fluid or swab from any body site. The most common site of colonisation is the anterior nares, but MRSA can also be found in other areas such as the axillae, abnormal skin (e.g., eczema, wounds), urine, rectum, and throat. There should be no signs or symptoms of infection. The colonised site may act as a reservoir of MRSA, which then causes infection at another site or can be passed on to others. Although the colonised patient (or staff member) does not need treatment, a course of decolonisation treatment may be given in order to eradicate carriage and prevent future infections or transmission. In this overview, we have included adults aged 18 years or older in hospitals and residential homes, outpatients, and healthcare workers.

Incidence/ Prevalence

The incidence of MRSA varies from country to country. The UK, Ireland, and southern Europe (e.g., Spain, Italy, and Greece) have a high incidence when compared with northern Europe and Scandinavia. The most objective measure of incidence is the percentage of S aureus found in blood cultures that are resistant to methicillin. Rates may exceed 40% in many countries.

Aetiology/ Risk factors

Traditional risk factors for MRSA colonisation include prolonged stay in hospital, severe underlying disease, prior antibiotics, exposure to colonised people, and admission to a high-risk unit (critical care, renal unit, etc). MRSA has primarily been a problem associated with exposure to the healthcare system. More recently, MRSA strains have emerged in the community (so-called community-associated MRSA [CA-MRSA] strains) that have no relationship with healthcare-related strains. These strains may colonise and cause infection among young, healthy people.

Prognosis

The virulence of MRSA, or its ability to cause death and severe infection, seems to be greater than that of methicillin-susceptible S aureus strains. A meta-analysis of 31 cohort studies found that mortality associated with MRSA bacteraemia was significantly higher than that of methicillin-susceptible S aureus bacteraemia (mean mortality not reported; OR 1.93, 95% CI 1.54 to 2.42).

Aims of intervention

To reduce the number of people colonised with MRSA or MRSA infection, with minimal adverse effects of treatment.

Outcomes

MRSA eradication rates, adverse effects.

Methods

Search strategy BMJ Clinical Evidence search and appraisal date June 2014. Databases used to identify studies for this systematic overview include: Medline 1966 to June 2014, Embase 1980 to June 2014, The Cochrane Database of Systematic Reviews 2014, issue 6 (1966 to date of issue), the Database of Abstracts of Reviews of Effects (DARE) and the Health Technology Assessment (HTA) database. Inclusion criteria Study design criteria for inclusion in this systematic overview were systematic reviews and RCTs published in English, any level of blinding, and containing more than 20 individuals, of whom more than 80% were followed up. Although there was no minimum length of follow-up required to include studies, we preferentially report outcomes at 1 month or longer; we only include outcomes evaluated at less than 1 month if the same outcome is not reported at a time point of 1 month or longer. BMJ Clinical Evidence does not necessarily report every study found (e.g., every systematic review). Rather, we report the most recent, relevant and comprehensive studies identified through an agreed process involving our evidence team, editorial team, and expert contributors. Evidence evaluation A systematic literature search was conducted by our evidence team, who then assessed titles and abstracts, and finally selected articles for full text appraisal against inclusion and exclusion criteria agreed a priori with our expert contributor. In consultation with the expert contributor, studies were selected for inclusion and all data relevant to this overview extracted into the benefits and harms section of the overview. In addition, information that did not meet our pre-defined criteria for inclusion in the benefits and harms section may have been reported in the 'Further information on studies' or 'Comment' sections (see below). Adverse effects All serious adverse effects, or those adverse effects reported as statistically significant, were included in the harms section of the overview. Pre-specified adverse effects identified as being clinically important were also reported, even if the results were not statistically significant. Although BMJ Clinical Evidence presents data on selected adverse effects reported in included studies, it is not meant to be, and cannot be, a comprehensive list of all adverse effects, contraindications, or interactions of included drugs or interventions. A reliable national or local drug database must be consulted for this information. Comment and Clinical guide sections In the Comment section of each intervention, our expert contributors may have provided additional comment and analysis of the evidence, which may include additional studies (over and above those identified via our systematic search) by way of background data or supporting information. As BMJ Clinical Evidence does not systematically search for studies reported in the Comment section, we cannot guarantee the completeness of the studies listed there or the robustness of methods. Our expert contributors add clinical context and interpretation to the Clinical guide sections where appropriate. Structural changes this update At this update, we have removed the intervention 'tea tree oil preparations' from this overview as this is no longer used clinically for eradicating MRSA colonisation. Data and quality To aid readability of the numerical data in our overviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). BMJ Clinical Evidence does not report all methodological details of included studies. Rather, it reports by exception any methodological issue or more general issue that may affect the weight a reader may put on an individual study, or the generalisability of the result. These issues may be reflected in the overall GRADE analysis. We have performed a GRADE evaluation of the quality of evidence for interventions included in this overview (see table ). The categorisation of the quality of the evidence (into high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the BMJ Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).

Table 1.

GRADE evaluation of interventions for MRSA colonisation (eradicating colonisation in people without active/invasive infection)

Important outcomes	MRSA eradication, adverse effects.
Number of studies (participants)	Outcome	Comparison	Type of evidence	Quality	Consistency	Directness	Effect size	GRADE	Comment
What are the effects of treatment for MRSA nasal or extra-nasal colonisation in adults?
3 (unclear)	MRSA eradication	Mupirocin nasal ointment v placebo	4	–1	–1	–2	0	Very low	Quality point deducted for incomplete reporting of results; consistency point deducted for statistical heterogeneity among RCTs; directness points deducted for co-intervention in 1 RCT (chlorhexidine body wash) and inclusion of people with MSSA in 1 RCT
1 (43)	MRSA eradication	Mupirocin nasal ointment v oral trimethoprim–sulfamethoxazole plus topical fusidic acid	4	–2	0	–2	0	Very low	Quality points deducted for sparse data and incomplete reporting of results; directness points deducted for highly selected population (ITU/surgical unit) and inclusion of people with MSSA infection
1 (103)	MRSA eradication	Antiseptic body wash v placebo	4	–1	0	–1	0	Low	Quality point deducted for sparse data; directness point deducted for use of co-intervention (mupirocin, oral rinses)

Type of evidence: 4 = RCT Consistency: similarity of results across studies. Directness: generalisability of population or outcomes.Effect size: based on relative risk or odds ratio.

Glossary

Low-quality evidence

Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Very low-quality evidence

Any estimate of effect is very uncertain.

Disclaimer

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