Evaluation of Staphylococcus aureus eradication therapy in orthopaedic surgery.

Tsang STJ1,3*, McHugh MP2, Guerendiain D2, Gwynne P3, Boyd J4, Laurenson IF2, Templeton KE2, S Lewis5, Simpson AHRW1, Walsh TS4

1. Department of Orthopaedic surgeryUniversity of EdinburghChancellor’s Building49 Little France CrescentOld Dalkeith Road EdinburghEH16 4SB

2. Department of Medical MicrobiologyRoyal Infirmary of Edinburgh51 Little France CrescentOld Dalkeith RoadEdinburghEH16 4SA

3. School of Biological sciences University of Edinburgh King's Buildings Mayfield Road Edinburgh EH9 3JR

4. Department of Anaesthesia, Critical care and Pain MedicineUniversity of EdinburghChancellor’s Building49 Little France CrescentOld Dalkeith Road EdinburghEH16 4SB

5. Edinburgh Clinical Trials UnitUniversity of Edinburgh Usher InstituteOld Medical SchoolTeviot PlaceEdinburghEH8 9AG

Word countMain text 3511References 1349Figures 71Tables 258*Corresponding author: Jerry.Tsang@ed.ac.uk

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Abstract

Purpose. Despite WHO recommendations there is currently no national screening and

eradication policy for the detection of methicillin-sensitive Staphylococcus aureus (MSSA) in

the UK prior to elective orthopaedic surgery. This study aimed to evaluate the effectiveness

of current standard methicillin-resistant S. aureus (MRSA) eradication therapies in the context

of S. aureus (both MRSA and MSSA) decolonisation in an elective orthopaedic population.

Methodology. A total of 100 patients awaiting joint replacement surgery who were positive

for S. aureus on PCR nasal screening underwent the current standard MRSA pre-operative

decolonisation regimen for five days. Prior to commencement of the eradication therapy

swabs of the anterior nares, throat, and perineum were taken for culture. Further culture

swabs were taken at 48-96 hours following treatment, at hospital admission for surgery, and

at hospital discharge. Following completion of treatment patients were asked to provide

feedback on their experience using Likert rating scales. The primary outcome of this study

was S. aureus clearance 48-96 hours following eradication treatment.

Results/Key Findings. Clearance of S. aureus 48-96 hours following treatment was 94%

anterior nares, 66% throat, and 88% groin. Mean completion with nasal mupirocin was 98%.

There was no statistically significant recolonisation effect between the end of the eradication

treatment period and the day of surgery (p>0.05) at a median time of 10 days.

Conclusion. Current MRSA decolonisation regimens are well-tolerated and effective for

MSSA decolonisation for the anterior nares and groin. The decolonisation effect is preserved

for at least 10 days following treatment.

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Abbreviations

BMI Body mass index

CI Confidence interval

IQR Inter-quartile range

HAI Hospital-acquired infection

MRSA Methicillin-resistant Staphylococcus aureus

MSSA Methicillin-sensitive Staphylococcus aureus

MANOVA Multivariate analysis of variance

PJI Periprosthetic joint infection

RR Relative risk

SSI Surgical site infection

UK United Kingdom

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Introduction

Healthcare associated infection (HAI) is a significant clinical issue. This is

particularly the case for surgical site infection (SSI). SSI is widely tracked as a quality

indicator in healthcare systems and reporting is mandatory in many settings. Orthopaedic

surgery is a primary focus of SSI surveillance given the very high rates of implant use. The

development of SSI has been shown to have major implications on patient-reported quality of

life and function, healthcare costs, and medicolegal costs (1). A national audit of orthopaedic

practice in the UK highlighted the wide variation in the prevalence of periprosthetic joint

infection (PJI), ranging from 0.2-5% (2). It was estimated that between £200-300 million

could be saved annually through standardisation of practice in the prevention of PJI across

the UK. Amongst mono-microbial SSIs following hip and knee replacements (around 75% of

all cases), 30-38% were methicillin-sensitive Staphylococcus aureus (MSSA), 4-5% were

methicillin resistant S. aureus (MRSA), and 25-28% were coagulase-negative staphylococci.

In poly-microbial infections Gram-positive organisms were implicated in 70-80% of cases

(3). High level nasal carriers of MSSA have a risk of health care-associated MSSA infection

that is 3-6 times the risk among non-carriers and low-level carriers. It is known that more

than 80% of health care-associated S. aureus infections are endogenous, implying acquisition

from sites on the patients’ own body (4,5). The association between nasal carriage of S.

aureus and SSI has been demonstrated in cohort studies (6,7) and a systematic review (8). A

pan-European study reported that 21.6% of healthy residents carry S. aureus in their nose,

with wide variation between countries (9). Amongst orthopaedic patients the prevalence has

been estimated to range from 20-36% (10,11). In contrast to MSSA, MRSA prevalence in

healthy community individuals is estimated to be <2% (12). A recent retrospective cohort

study in the UK reported a three-fold reduction in MSSA-associated SSI with a routine pre-

operative screening and decolonisation programme amongst patients undergoing elective

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orthopaedic surgery (13). Screening of patients presenting for surgery or admitted to hospital

areas with strong risk factors for MRSA (e.g. intensive care units, dialysis units, and elderly

care areas) is widely practiced in healthcare systems and is a part of national SSI-prevention

strategies. There are currently no national screening policies for MSSA in the UK prior to

orthopaedic surgery despite recent WHO recommendations (14). This study aimed to

evaluate the effectiveness of current MRSA eradication therapies in the context of S. aureus

decolonisation prior to joint replacement surgery.

Methods

This study was conducted at a university teaching hospital from October 2015 to

September 2016. The study protocol was reviewed and approved by the regional ethics

committee. Patients presenting for assessment prior to orthopaedic implant surgery were

prospectively enrolled and consented into the study. Pre-operative screening via a swab of the

anterior nares was undertaken using the Xpert® S. aureus Nasal Complete Assay (Cepheid).

Those positive for S. aureus (either MSSA or MRSA) on nasal PCR screening were invited to

participate in the study. Once enrolled further swabs of the anterior nares, throat, and

perineum were taken for culture assays. To ensure detection of both MRSA and MSSA, swabs

were subcultured onto Brilliance MRSA 2 Agar® and mannitol salt agar (Oxoid,

Basingstoke, UK). Antibiotic sensitivity testing was performed on the VITEK® 2 system

(bioMérieux, Marcy-l’Étoile, France).

All enrolled patients received a five-day decolonisation regimen comprised of nasal

mupirocin 2% ointment applied to the inner surface of each anterior nares (three times daily),

chlorhexidine gluconate 0.2% mouthwash solution to be gargled and used to rinse the

oropharynx (twice daily), and chlorhexidine gluconate 4% (Hibiscrub) solution to be used as

a soap / shampoo substitute (once daily). Patients were required to keep a daily record

documenting their ability to administer the above decolonisation regimen including

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concordance with personal hygiene habits as recommended by the study institute’s MRSA

decolonisation policy. Patients were excluded on grounds of known chlorhexidine allergy,

peri-operative systemic antibiotic treatment, known colonisation by mupirocin- or

chlorhexidine-resistant S. aureus, pregnancy or breast-feeding, or age <16 years.

In addition to S. aureus colonisation status the following baseline information was

also collected: age, gender, ethnicity, body mass index (BMI), aetiology of joint disease,

planned surgical procedure, concurrent medication, functional comorbidity index,

documented MSSA or MRSA infection during previous 12 months (plus site), hospital

admissions within the past 12 months, date of last hospital admission, admission to a long

term care facility or a rehabilitation facility within the past 12 months, usual residence, any

surgical interventions within the past 12 months, presence of indwelling urinary catheter or

other implant device, antibiotic use within the past 3 months, signs or symptoms of current

respiratory infection, and presence of skin lesions.

Further culture swabs were taken at 48-96 hours after completion of the five-day

eradication regimen. Additional swabs were taken at hospital admission for surgery (or day

21-28 for participants with postponed or cancelled surgery) and at either hospital discharge or

14 days post-surgery (whichever occurred first). Patients were followed up for six weeks

post-surgery. Following the five-day treatment period patients were asked to provide

feedback on their experience using Likert rating scales.

The primary outcome of this study was the proportion of S. aureus clearance at 48-96

hours following the eradication treatment period. Secondary outcomes were the proportion of

S. aureus clearance at hospital admission and hospital discharge, development of a hospital

acquired infection, length of stay in acute hospital care, discharge destination, development

of a surgical site infection, and history of infections requiring antibiotics following hospital

discharge.

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Statistical analysis.

Data were analysed using Minitab v17 (Minitab Ltd, UK). Fisher’s exact testing or

Chi-squared analysis were used to compare categorical data, Student’s T-test was used in the

analysis of univariate continuous data, and a multivariate analysis of variance (MANOVA)

was used for multivariate continuous data. A p-value <0.05 was deemed to be statistically

significant.

Results

A total of 273 patients were consented, enrolled, and underwent nasal PCR screening

in this study. A total of 100 patients were found to be positive for nasal S. aureus. There

were 14 patients withdrawn from the study prior to commencement of the eradication therapy

(Fig. 1). Of the 86 full participants, 81 were found to be colonised with MSSA and 5

colonised with MRSA. All isolates were mupirocin sensitive. Baseline characteristics of the

enrolled patients are shown in Table 1. A further two patients were withdrawn as they could

not complete the five-day course of eradication therapy as the date of their surgery was

brought forward. Surgery was cancelled for ten patients, who were followed-up for a second

and final time 21-28 days following the eradication therapy. The remaining 74 patients went

on to have their joint replacement surgery with all patients being assessed on hospital

admission and discharge. All patients received prophylactic antibiotics (Cefuroxime 1500mg

30mins prior to skin incision and two further doses Cefuroxime 750mg eight hourly) and

surgical skin preparation (Chlorhexidine Gluconate 0.5% (Hydrex® Ecolab, Leeds,

UK)/Povidone-Iodine 10% (Videne® Ecolab, Leeds, UK) in the perioperative period.

Following this eight patients were lost to final follow-up (six weeks post-surgery) as they

could not be contacted for confirmation of the visit (Fig. 1)

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A single patient (1.2%) had a MRSA positive respiratory infection within twelve

months prior to enrolment onto this study. There were twelve patients (14.0%) who had been

admitted to a hospital in the previous twelve months, eleven (12.8%) of whom were for the

purposes of surgical intervention. Surgical interventions occurred at a median time of five

months (IQR 3-9) prior to inclusion in this study. There was no longstanding indwelling

medical device or catheter-use amongst the enrolled patients. There were eleven (12.8%)

participants who had undergone and completed antibiotic therapy within the previous three

months, at a median time of one month (IQR 1-2 months). Almost all participants lived in

their own home with only two patients (2.3%) residing in long-term care facilities.

Patient completion of the eradication regimen is presented in Table 2. Completion

was defined as the number of the treatments reported to have been administered by each

participant divided by the total number of prescribed treatments. Mean completion of nasal

mupirocin was 98.2% (SD ±5.2). All other aspects of the eradication regimen, except for daily

changes of bed sheets (61.2% (SD ±31.5), also had >90% completion. Full compliance was

defined as no deviation from eradication regimen (Table 3) i.e. all the prescribed treatments

for a particular element were completed by the participant. Only 19/85 (22.3%) reported full

compliance with the entire regimen. There was full compliance to the nasal mupirocin

regimen in 69/85 (81.2%). Unsurprisingly full compliance was lowest with respect to daily

changes of bed sheets (26/85 (30.6%).

Following the treatment period 78% patients strongly agreed that the regimen did not

cause discomfort, 96% patients were in strong agreement that the treatment was painless, and

79% patients in strong agreement that the treatment was acceptable (Fig. 2).

The clearance of S. aureus 48-96 hours following treatment from the anterior nares

was 93.8% (95% Confidence Interval (CI) 79.2-99.2%), from the throat 65.6% (95% CI 46.8-

81.4%), and from the groin 87.5% (95%CI 71.0-96.5%) (Fig. 3). There were no statistically

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significant differences in colonisation between the first follow-up (48-96 hours following the

eradication treatment period) and the day of surgery (p>0.05) (Fig. 3). Surgery was

performed at a median time of 9.5 days (IQR 6-13 days) following the eradication treatment

period. No statistically significant associations between treatment completion and

decolonisation at time of surgery were demonstrated on comparative analysis (p>0.05). Final

swabs were taken on discharge at a median time of four days (IQR 3-5 days) from the date of

surgery and showed evidence of further decolonisation (Pre-op 43.8% (95% CI 26.4-62.3%)

vs. Post-op 84.0% (95% CI 63.9-95.5%), p=0.003). However only the improvements in S.

aureus decolonisation from the throat (Pre-op 66.7% (95% CI 47.2-82.7% vs. Post-op 92.0

(95% CI 74.0-99.0%), p=0.046) and groin (Pre-op 76.7% (95% CI 57.7-90.1%) vs. Post-op

96.0 (95% CI 79.6-99.9%), p=0.026) were found to be statistically significant.

All patients were discharged back to their home accommodation. There was a single

episode of a HAI, in the form a urinary tract infection, during the admissions. Of the 66

patients available for follow-up at six weeks, three patients reported surgical/anaesthetic site

infections. Two of these were at the operative site and one at the site of their spinal

anaesthetic. All were treated with oral antibiotics. A further three patients required antibiotic

therapy for urinary tract infections. There were no reported deep infections or requirement for

revision surgery.

Discussion

The prevention of PJI is currently a hot topic in the field of orthopaedics. The

publication of a national audit highlighted the wide variation in the prevalence of PJI across

the UK (0.2-5%) (2). It was estimated that between £200-300 million could be saved annually

through standardisation of practice across the UK in the prevention of PJI. The most recent

joint registry data recorded ~182,000 primary joint replacements being performed in the UK

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in 2015 (15,16). From previous studies it is estimated that 45,000-66,000 of these patients

were colonised with MSSA (10,13) prior to joint replacement surgery . Nasal MSSA

colonisation has previously been reported to confer a 7.7% (95% CI 5.4-10.8%) absolute risk

of S. aureus PJI in elective orthopaedic patients (17). Screening and eradication programmes

prior to elective orthopaedic surgery are reported to confer a 66.4% (95% CI 45.8-87.0%)

relative risk reduction for the prevention of S. aureus PJI (13,17–21). Therefore 1000-6200

cases of S. aureus PJI per annum could potentially be prevented in the UK with the creation

of a national MSSA screening and eradication programme in line with the latest WHO

recommendations (14). It has been previously estimated that the total hospital costs of PJI

treatment are between £20,000-£100,000 per case (2,22), therefore a national S. aureus

decolonisation programme could result in £20 million-£620 million worth of savings in

avoided treatment costs.

Systematic reviews of the efficacy and cost effectiveness of MRSA screening and

eradication programmes conclude that treatment with mupirocin nasal ointment (three times

daily for five days) combined with antiseptic wash (once daily for five days) as the optimum

intervention (23). Although the proportion of MRSA clearance two days after completion of

the regimen has been reported to be as low as 53% (24), it remains the most widely used

approach, especially when combined with changing of bed sheets (23). Using the same

regimen in this study for patients colonised with S. aureus (MSSA or MRSA) there was 94%

clearance from the anterior nares, 66% from the throat, and 88% from the groin. There was

evidence of further decolonisation of the throat and groin during the patient’s admission to

hospital. This was likely due to the use of perioperative prophylactic antibiotics and surgical

skin preparation, which was received by all the participants enrolled in this study. Chen et al

(25) reported an 83% (20/24) clearance of nasal MSSA in elective orthopaedic patients, using

a five day course of nasal mupirocin and chlorhexidine body wash. A similar level of MSSA

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elimination from the nose in elective orthopaedic patients was also reported by Kalmeijer et

al (84%, 80/95) using a five-day course of nasal mupirocin only. In an analysis of six clinical

trials, Doebbeling et al (26) reported a pooled proportion of elimination of 91% (range 68%–

100%) for healthy volunteers who received a five day course of mupirocin twice per day.

The effectiveness of mupirocin in the decolonisation of S. aureus (both MSSA and MRSA)

nasal carriers was reported in a meta-analysis to be up to 90% at one week and but only 65%

after two weeks. In a further meta-analysis of topical nasal mupirocin effectiveness, its use in

MRSA colonised cohorts (Relative risk (RR) of treatment failure 0.71, 95% CI 0.55-0.90) was

reported to be less effective than when used in MSSA (RR 0.52, 95% CI 0.43-0.64) or mixed

(MRSA and MSSA) cohorts (RR 0.30, 95% CI 0.24-0.38) (8). This should be considered when

interpreting the results presented in our study given the proportion of MSSA in our mixed S.

aureus cohort. Treatment failure was reported to be associated with bacterial resistance to

mupirocin, extra-nasal colonisation, and longer hospital stays (8). A further reason for

treatment failure may be the intensity of decolonisation protocols (especially when carried

out at the patient’s home) resulting in low patient compliance. A further explanation that has

been postulated for low treatment completion is poor patient tolerance of nasal mupirocin. A

recent survey study found 39% of orthopaedic patients undergoing pre-operative

decolonisation described “unpleasant or very unpleasant symptoms” associated with

treatment (27).

One study of nasal decolonisation in non-orthopaedic patients found a 75% failure in

nasal MRSA eradication due to mupirocin resistance, both low and high level resistant

organisms (28). Low-level resistance is defined as a minimum inhibitory concentration of 8

to 256 mg/L and is mediated by a point mutation in the gene coding for isoleucyl-tRNA

synthetase. High-level resistance is defined as a minimum inhibitory concentration of ≥512

mg/L and is mediated by the acquisition of a plasmid containing the mupA gene, which

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encodes for an alternative isoleucyl-tRNA synthetase (29). The prevalence of high level

mupirocin resistance in the United States of America has previously been estimated to be

3.3% (30). The absence of mupirocin-resistant organisms in our cohort has undoubtedly

contributed to the high levels of treatment success seen in this study and our data should be

interpreted within this context.

Topical agents such as chlorhexidine or triclosan body wash are recommended for

patient-administered preoperative skin preparation as they have been shown to decrease

bacterial counts on the skin (31). They are often used as adjuncts to topical nasal mupirocin

ointment in decolonization protocols to reduce bacterial density at extra-nasal sites. Recently

2% chlorhexidine wipes have been introduced to improve ease of administration and have

been shown to be as effective as 4% chlorhexidine solution in reducing bacterial skin counts

(32). Several studies have also examined whether chlorhexidine wipes used as empiric

preoperative monotherapy can reduce PJI risk after total hip or knee arthroplasty. These

studies, which did not screen for S. aureus carrier status (33–35), have reported mixed results.

The application protocols in these studies varied greatly. Those that instructed patients to

apply the 2% chlorhexidine wipes preoperatively to six anatomic sites (head and neck, both

arms, both legs, and the surgical site (33,34)) were found to be effective in reducing the risk

of PJI. Other studies that instructed patients to only apply wipes to the surgical site (35) were

not effective in reducing the risk of PJI. In this study chlorhexidine body wash alongside

daily changes of clothes, towels, and bed sheets was found to be effective in decolonisation

of the groin. However, the effectiveness of chlorhexidine mouthwash (66%) was limited

despite high-levels of patient–reported treatment completion.

Overall treatment completion in this study was high (>90%), with the exception of

daily changes of bed sheets (31%). On the whole, patients thought the decolonisation was

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acceptable (79%) and did not cause pain (96%). Yet despite this only 19/85 (22%) reported

full compliance

with the entire regimen and 69/85 (81%) reported full compliance to the nasal mupirocin

regimen. However this is higher than in previous studies that have assessed patient

compliance with pre-operative S. aureus eradication bundles. Schweizer et al reported that

only 39% of patients undergoing elective cardiothoracic surgery were fully compliant with a

regimen that involved the use of topical mupirocin and chlorhexidine body wash.

Clearance was preserved at all sites up to the day of surgery at a median time of 10

days from the end of the treatment period. Recolonisation is highly relevant but poorly

understood and studied. Studies indicate there are broadly two groups of patients, those who

are transiently colonised and quickly lose S. aureus, and those who are persistent carriers for

whom S. aureus becomes established as part of their “normal” flora (36). These populations

may respond differently to eradication regimens, and have different recolonisation profiles.

This is particularly relevant to managing risk of cross colonisation/infection between patients

and healthcare workers. Long term studies suggest that 30% of successfully treated patients

remain decolonised after 12 months (37). Repeated eradication treatment is not recommended

because it may promote the development of mupirocin resistance. The effect of widespread

decolonisation, in particular mupirocin treatment, on infections caused by organisms other

than S. aureus is also of concern. A Cochrane systematic review concluded that although

mupirocin treatment of S. aureus carriers is effective at reducing infections caused by S.

aureus it may increase the incidence of infections with other organisms (38).

A potential argument against the inclusion of mupirocin in decolonisation regimens is

the development of resistance (39), with prior therapeutic use having been shown to increase

the risk of resistance in MRSA carriers by nine-fold (40). A systematic review reported that

there was a 1% risk of resistance with short-term prophylaxis (8). Other studies have noted

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evidence for increasing low-level mupirocin resistance associated with increased mupirocin

consumption (41). The relevance of mupirocin resistance to development of healthcare

associated infection is uncertain, but it remains the chief concern limiting its widespread use

in this context, leading to the exploration of alternative decolonisation strategies (29). Other

methods of decolonisation include phototherapy-based disinfection, total body chlorhexidine

gluconate wipes preoperatively, and iodine-based solutions applied hours before surgery (37).

Chlorhexidine gluconate wipes (2%) eliminate the need to bathe just before surgery and have

started to gain popularity and prominence in the orthopaedic literature (42).

This study presents a comprehensive evaluation of the effectiveness of current MRSA

eradication therapy in the context of S. aureus eradication. Its effectiveness has been

described across a number of clinically relevant-time points and anatomic sites. It also

quantified patient compliance for each aspect of the treatment and their overall perceptions of

the regimen. However these results should be taken in the context of possible selection bias.

The patients recruited to this study would have been likely to be highly motivated, thus

leading to high patient compliance, positive feedback, and high efficacy of the treatment. The

patient diary and regular follow-up encounters would have also created an additional

Hawthorne effect (43,44), further improving patient-reported compliance. A further limitation

of this study was that strain typing was not performed. It is therefore possible that the study

isolates belong to a single clonal lineage. However, the patients included in our study were

identified as carriers over a period of 12 months and none were involved in known

transmission clusters, so clonal relationships between isolates are less likely. In addition,

unpublished strain typing of S. aureus from our health board showed that the population was

diverse, containing multiple strain types (Andrew Robb, personal communication). Future

recommended studies include analysis of S. aureus clearance dynamics to optimise the

treatment regimen. A shorter treatment period would allow it to be applied to emergency

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surgery patients, improve patient compliance, and reduce the development of antimicrobial

resistance (45).

In conclusion this study found that current MRSA decolonisation regimens were well-

tolerated and effective in pre-operative MSSA decolonisation of the anterior nares and groin.

This effect was preserved for at least 10 days following treatment.

Funding information. This work was supported by the Royal College of Surgeons

Edinburgh, Edinburgh, United Kingdom (RCSEd/Cutner research fellowship awarded to

SJT) and Leonardo (Selex Medical), Edinburgh, United Kingdom (Research grant awarded to

TSW).

Acknowledgements. This authors would like to thank the Orthopaedic department Research

nurses, Microbiology Biomedical Scientists, and the Edinburgh Clinical Trials Unit for the

support received during the data collection and processing.

We thank Andrew Robb from the Scottish MRSA Reference Laboratory, Glasgow, UK for

providing typing data on S. aureus.

Conflicts of interest. The authors declare that there are no conflicts of interest.

Ethical statement. This study was approved by the South-east Scotland Research Ethics

Committee (reference 15/SS/0091) and witnessed consent was obtained from all enrolled

patients.

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Table 1. Baseline characteristics of participants undergoing S. aureus eradication therapy.

Total N=86Age Median (Q1-Q3) 65 years (57-72)Gender Female 56 (65.1%)Ethnicity White 85 (98.8%)

Asian 1 (1.2%)BMI Median (Q1-Q3) 31 kg/m2 (27-36)Planned orthopaedic procedure Primary total hip replacement 30 (34.8%)

Primary knee replacement 48 (55.8%)Primary bilateral knee replacements 1 (1.2%)Primary unicompartmental knee replacement 1 (1.2%)Primary total shoulder replacement 1 (1.2%)Primary total ankle replacement 1 (1.2%)Revision total hip replacement 1 (1.2%)Revision total knee replacement 3 (3.5%)

Days to planned procedure Median (Q1-Q3) 15 (12-19)Aetiology of joint disease Osteoarthritis 83 (96.5%)

Rheumatoid arthritis 2 (2.3%)Seronegative inflammatory arthropathy 1 (1.2%)

Co-morbidities Asthma or COPD* 18 (20.9%)Ischaemic heart disease 11 (12.8%)Congestive cardiac failure 2 (2.3%)Cerebrovascular disease 2 (2.3%)Peripheral vascular disease 1 (1.2%)Diabetes (Type I and type II) 8 (9.3%)

*Chronic obstructive pulmonary disease

Table 2. Patient reported completion with eradication therapy

Mean (standard deviation)Overall 90.4 (±10.1)Nasal mupirocin (3 times/day) 98.2 (±5.2)Chlorhexidine mouthwash (twice/day) 98.8 (±6.1)Daily change of bedding 61.2 (±31.5)Daily change of towels 93.6 (±18.6)Daily change of clothing 96.0 (±12.6)Daily chlorhexidine body wash 94.8 (±16.9)

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Table 3. Patient reported full compliance with eradication therapy i.e no deviation from regimen

Total (n=85)Entire regimen Yes 19 (22.3%)Nasal mupirocin (3 times/day) Yes 69 (81.2%)Chlorhexidine mouthwash (twice/day) Yes 80 (94.1%)Daily change of bedding Yes 26 (30.6%)Daily change of towels Yes 72 (84.7%)Daily change of clothing Yes 75 (88.2%)Daily chlorhexidine body wash Yes 75 (88.2%)

Figure 1. Consort diagram of enrolled study patients

Figure 2. Summary of patient feedback, using Likert rating scales, following the treatment period. Each questionnaire was scaled 0-10 where: 0 means strongly agree, 5 means uncertain, and 10 means strongly disagree.

Figure 3. S. aureus clearance following eradication therapy according to site and sampling time point. Statistically significant differences within site groupings denoted by *.

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