Volume 75, Issue 1, Pages 47-50 (January 2007)

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ABSTRACT

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Methicillin-resistant Staphyloccocus aureus (MRSA) isolation from diabetic foot ulcers correlates with nasal MRSA carriage

Received 30 November 2005; accepted 31 May 2006. published online 12 September 2006.

Abstract

Methicillin-resistant Staphylococcus aureus is increasingly isolated from diabetic foot ulcers, and may be associated with an adverse prognosis. We have explored the relationship between MRSA isolation from foot ulcers and nasal MRSA carriage. Over a 12 month period, 65 consecutively attending patients with diabetic foot ulceration were recruited. Demographic information was collected, and the ulcer and nose swabbed bacteriologically using standard techniques. The patients were mean age 61year, diabetes duration 14 year, and HbA1c 8.5%. There were 61% male and 85% with type 2 diabetes. Ulcers were neuropathic in 55%, ischaemic in 14% and neuroischaemic in 31%. MRSA was isolated from 12 (19%) ulcers, and 11 (17%) had nasal carriage. Of the MRSA positive ulcer patients 7/12 (58%) had nasal MRSA carriage, compared with 4/53 (8%) with MRSA negative ulcers (p<0.0003). We conclude that nasal MRSA carriage in diabetic patients is a significant risk factor for foot ulcer MRSA infection.

Keywords: Diabetes mellitus, Foot ulceration, MRSA, Staphylococcus aureus, Nasal carriage

Article Outline

• Abstract

• 1. Introduction

• 2. Patients and methods

• 3. Results

• 3.1. Patient characteristics

• 3.2. Bacteriology of ulcers

• 3.3. Nasal MRSA

• 3.4. Statistical analysis

• 4. Discussion

• References

• Copyright

1. Introduction

Foot ulceration in diabetes mellitus is a serious complication. For example, it is a contributory factor in over 80% of lower limb amputations in diabetic patients [1]. Foot ulcer patients also have a longer stay in hospital than diabetic patients admitted for other reasons [2]. Infected ulcers take longer to heal, and further increase the risk of amputation [3], which is itself a predictor of mortality in diabetes, mainly from vascular disease [4], [5]. Foot ulcers themselves are independent risk factors for death [6], [7].

Infection with methicillin-resistant Staphylococcus aureus (MRSA) is an increasing problem in both hospital and the community [8], [9]. MRSA is now commonly grown from foot ulcer swabs of diabetic patients [10], and such isolates appear to be increasing in frequency [11]. In this study, we have investigated the prevalence of MRSA carriage in our Diabetic Foot Clinic, and assessed the characteristics and correlates of such patients. We have also explored the relationship between MRSA ulcer infection and nasal MRSA carriage.

2. Patients and methods

The study was carried out at the Diabetic Foot Clinic of the Walton Diabetes Centre, University Hospital Aintree, Liverpool. Over a 12 month period, 65 consecutively attending patients with foot ulceration were prospectively recruited. Data recorded included age, diabetes duration, type of diabetes, treatment, and most recent (within the last 6 months) glycosylated haemoglobin (HbA1c) level. HbA1c was measured by a high-performance liquid chromatography (HPLC) method which was DCCT-aligned (non-diabetic range 4.5–6.0%). Peripheral sensory neuropathy was considered present if three or more sensory modalities were absent [12]. Peripheral vascular disease (PVD) was diagnosed if both foot pulses (dorsalis pedis and posterior tibialis) were absent on palpation from the ulcer-affected limb. Neuroischaemic ulceration was diagnosed if criteria for both PVD and sensory neuropathy were met.

Ulcers were swabbed using a transportable cotton swab (Technical Services Consultants Ltd., Heywood, UK) applied with firm rolling pressure to the base of the ulcer after debridement. All patients had single ulcers only. It was transported to the laboratory in medium, and plated for culture on blood agar, cysteine lactate electrolyte deficient agar, and selective staphylococcal and streptococcal agar. Swabs were similarly taken from both nostrils, and treated microbiologically in the same way. For swabs on both sites, MRSA was identified using standard techniques [13].

Data from clinical proformas was transferred to a Microsoft Excel spreadsheet, and statistically analysed using a StatsDirect package. Chi-testing was used for proportionate data, and logistic regression analysis of all measured variables was used to predict association with MRSA positive ulcers.

3. Results

3.1. Patient characteristics

These are shown in Table 1. In common with other reports [14], most had type 2 diabetes, were elderly or in late middle-age, and there was a male predominance. The majority of ulcers were neuropathic or neuroischaemic (86%).

Table 1.

Patient characteristics

	Number of patients	65
	Age (mean with range)	61 (25–88)
	Duration of diabetes (mean with range)	14 (1–48)
	Male:female ratio	46:19 (61%:29%)
	Type 1:type 2 ratio	10:55 (15%:85%)

	Treatment
	Diet	3 (4%)
	Drugs	31 (48%)
	Insulin	31 (48%)

	HbA1c (mean with range)	8.5% (4.8–13.6%)

	Type of ulcer
	Neuropathic	36 (55%)
	Ischaemic	9 (14%)
	Neuroischaemic	20 (31%)

3.2. Bacteriology of ulcers

This is summarised in Table 2. There were 67% with positive swab isolates, 42% with S. aureus isolated, and 12 (19%) with MRSA.

Table 2.

Bacteriological results

	Total patients	65
	Positive bacterial isolates	44 (67%)
	Staphylococcus aureus (total)	27 (42%)
	MSSA	15 (23% of total, 56% of all S.aureus)
	MRSA positive	12 (19% of total, 44% of all S.aureus)

	Other organisms:
	Coliforms	7
	Haemolytic streptococci	7
	Enterobacter	6
	Anaerobes	5
	Pseudomonas	5
	Proteus	4
	Diphtheroids	2

Note: MSSA, methicillin-sensitive Staphylococcus aureus; MRSA, methicillin-resistant Staphylococcus aureus.

3.3. Nasal MRSA

MRSA was isolated from 11 (17%) of the 65 studied patients. A total of 16 patients had MRSA grown from either their ulcers or nose. In seven, both nose and ulcer were positive for MRSA, in five MRSA was cultured from the ulcer but not the nose, and in four there was nasal MRSA carriage but the ulcer was MRSA negative.

3.4. Statistical analysis

Of the 12 patients with ulcers MRSA positive, 7 (58%) had nasal MRSA carriage. However, of the 53 patients with ulcers MRSA negative, only 4 (8%) had nasal MRSA carriage (p<0.0001). Comparing MRSA positive and negative foot ulcer patients, there was no significant difference in age, diabetes duration, cause of ulcer, or HbA1c level. Multiple logistic regression analysis was also carried out, using the variables of age, type of diabetes, diabetes duration, HbA1c, cause of ulcer and nasal MRSA carriage, as potential variables which may predict MRSA positive ulcers. A significant predictive value was only found for nasal MRSA carriage (p=0.0003). The odds ratio for having an MRSA positive foot ulcer if a patient had nasal MRSA carriage was 17.2 (95% confidence intervals 3.7–79.6).

4. Discussion

There is relatively little information on the relationship between MRSA infection and diabetic foot ulceration. A study from Manchester, UK, of a similar population to our own, found that 12/75 cases grew MRSA from ulcer swabs (15%) [10]—a similar proportion to our figure of 12/65 (19%). A larger series from France showed MRSA to be present in 29/180 (16%) of diabetic foot ulcers [15]. There is also some evidence that MRSA infection is increasing—a further report from Manchester has shown an increase in ulcer MRSA positivity from 15% in 1998 [10] to 30% in 2001 [11]. These results are important as MRSA infection may delay healing time [10].

Nasal carriage of Staphylococci is known to increase the risk of more widespread infections in affected individuals [16]. Nasal S.aureus appears more common in diabetic ulcer patients compared to non-diabetic control subjects (39% versus 25%, p<0.05) in one study from London [17]. This study also showed that genotyping demonstrated that the same strain of S.aureus was present in nose and ulcer in 92% of the diabetic foot ulcer patients [17]. Our own work reported here has shown that nasal carriage of MRSA is very strongly associated with MRSA ulcer infection. From the report of Hill et al. described above in Ref. [17], it seems likely that the MRSA strain in nose and ulcer is the same.

A problem of our study, and others on the same subject, is that of whether MRSA cultured from a diabetic foot ulcer is truly an infecting organism, or whether it is simply in a state of “carriage” or “colonisation”. Even with ulcer debridement, a swab for culture may not truly represent the organism causing infection in deeper tissues [18], [19]. This may partially explain why reports on the outcome of diabetic foot ulcers growing MRSA on culture show variable outcomes compared with non-MRSA infected ulcers [10], [20], [21].

Our study adds to current knowledge on MRSA and diabetic foot ulceration by demonstrating a close association between nasal MRSA carriage and foot ulcer MRSA infection. It seems likely that foot ulcer infection originated from nasal carriage, but we cannot exclude the reverse process, i.e. primary MRSA ulcer infection, followed by secondary nasal carriage. Nevertheless, an important question is whether eradication of nasal MRSA may reduce foot ulcer MRSA infection, and this is an avenue of research we plan to explore.

References

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Department of Diabetes and Endocrinology, University Hospital Aintree, Liverpool L9 1AE, United Kingdom

Corresponding author. Tel.: +44 151 529 4749; fax: +44 151 529 4688.

PII: S0168-8227(06)00327-5

doi:10.1016/j.diabres.2006.05.021

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