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Age and Ageing 2006 35(1):42-47; doi:10.1093/ageing/afj019
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Published by Oxford University Press on behalf of the British Geriatrics Society 2006 All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

The role of selective decontamination of the digestive tract in acute stroke

M. Gosney1, M. V. Martin2 and A. E. Wright3

1 The Institute of Health Sciences, Building 22, London Road, Reading RG1 5AQ, UK
2 Department of Clinical Dental Sciences, The Edward’s Building, University of Liverpool, Daulby Street, Liverpool L69 3GN, UK
3 Infection Surveillance, Royal Liverpool University Hospital, Prescot Street, Liverpool L7 8XP, UK

Address correspondence to: M. Gosney. Fax: (+44) 118 322 6544. Email: m.a.gosney{at}reading.ac.uk


   Abstract
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 Abstract
Introduction
 Methods
 Results
 Discussion
 Key points
 Source of funding
 References
 
Background: following a stroke, morbidity and mortality is high, with aspiration pneumonia being a common complication.

Objectives: to determine the levels of colonisation by and isolation of aerobic Gram-negative bacteria (AGNB) in acute stroke patients and determine the effect of selective decontamination of the digestive tract (SDD) on oral flora and whether it reduces both morbidity and mortality after an acute stroke.

Design: a prospective, randomised, placebo-controlled double blind trial.

Setting: acute stroke assessment units of three hospitals in the northwest of England.

Subjects: 203 patients admitted to hospital following a first acute stroke.

Methods: participants were randomised to SDD oral gel or placebo. Swallow was assessed on admission to hospital, and oral swabs were obtained thrice weekly. Demographic and clinical data were recorded.

Results: 203 patients (106 males and 97 females) participated, of whom 20 died during their hospitalisation, 19 withdrew and full follow-up was obtained for the remaining 164. A total of 122 AGNB were isolated in 105 samples from 48 patients. Abnormal swallow on admission was found in 58 patients (29%). A total of 34 patients carried a single gram-negative micro-organism that was present on one or more occasions. More than one AGNB was carried in 14 patients, and organisms were significantly more likely to be isolated from the placebo group than the active group during weeks 2 and 3 of treatment (P = 0.034, chi-squared). Seven patients in the placebo group and one in the treatment group developed pneumonia (P = 0.029, Fisher’s exact test).

Conclusions: high carriage of and colonisation by AGNB was found within this study, which was reduced by the addition of SDD. Although SDD reduced the presence of both organisms and documented episodes of pneumonia, mortality remained unchanged.

Keywords: stroke, selective decontamination, aspiration pneumonia, elderly


   Introduction
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 Abstract
 Introduction
Methods
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 Discussion
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 References
 
Stroke is a common and serious health problem in the UK. In 1999, 56,000 (11%) deaths in England and Wales were due to stroke [1], and the cost of caring for such patients consumes ~4–6% of the National Health Service budget annually [2, 3]. With increases in the number of elderly people, a 30% increase of first ever stroke by 2023 is predicted [4], and targets for reductions in post-stroke morbidity and mortality are therefore vital [3, 5].

Dysphagia after stroke is important as it may lead to dehydration or poor nutrition and may be associated with aspiration and pneumonia in up to 60% of patients [6].

Smithard et al. found that 51% of stroke patients were at risk of aspiration, and although many swallowing problems resolved in the first 3 days following stroke, 27% were still at risk at the end of a week and a smaller group (8%) continued to have swallowing problems for up to 3 months [7]. Dysphagia persisting for more than 3 weeks is associated with a less favourable outcome [8]. Six clinical indicators distinguish stroke patients who are at increased risk of aspiration: abnormal cough, abnormal gag reflex, dysphonia, dysarthria, voice change and cough after swallow [9].

Aspiration pneumonia occurs when large volumes of gastric contents, including food, are aspirated [10], although this is actually aspiration pneumonitis. Indeed, smaller amounts of material, e.g. saliva, may be aspirated and may contain a bacterial load sufficient to induce pneumonia, especially in a debilitated patient. Silent microaspiration may occur without being readily apparent, and aspiration pneumonia is generally bacterial in origin, with aerobic Gram-negative bacilli (AGNB) being the most frequently isolated micro-organisms [11]. Previous research has demonstrated oral carriage of AGNB in acute and rehabilitation stroke patients [12, 13].

Aspiration pneumonia continues to be a problem, with up to 6% of patients dying from the condition during the first year after a stroke [14].

The healthy oropharynx consists predominately of facultative Gram-positive bacteria such as alpha-haemolytic streptococci, with AGNB being found transiently [15, 16]. The healthy individual can resist AGNB, although humans do carry these organisms from day 2 of life [17]. Carriage, the presence of a bacterium on two consecutive samples, and isolation, the presence of a bacterium on one occasion, are rare in health. Normal flora performs four functions that prevent colonisation by potentially pathogenic bacteria:

  1. they occupy receptor sites on all mucosa, thereby inhibiting adherence by AGNB;
  2. they consume the available nutrients, thereby starving out AGNB;
  3. they produce substances that are actively toxic to AGNB; and
  4. they promote normal physiologic processes including mucosal cell renewal, which contributes to the clearance of AGNB.

In the UK, 7% of denture wearers have AGNB, but they are not found in non-denture wearers [18]. Colonisation correlates with the severity of illness: 37% in the moderately ill and 73% of seriously ill patients [19], with similar findings in acute stroke patients versus rehabilitation patients [12].

One intervention aimed at the prevention of aspiration pneumonia involves the use of selective decontamination of the digestive tract (SDD). First described in 1980 [20], SDD is a prophylactic technique in which antimicrobials eradicate AGNB from the oropharynx, whilst preserving the normal oral microbial flora. SDD has reduced aspiration pneumonia in those requiring artificial ventilation or who are immunosuppressed. In its full form, SDD has four components: oral gel containing a combination of carefully chosen antimicrobial drugs, applied topically to the mouth four times daily; a liquid suspension containing the same antimicrobials, administered via a nasogastric tube; a 3 day course of intravenous antimicrobials; and lastly, stringent infection control measures. No study has previously used SDD in stroke patients.

In our study, we planned to recruit stroke patients who were acutely but not critically ill and to eradicate AGNB from the oropharynx.


   Methods
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 Methods
Results
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 References
 
A prospective, randomised, double-blind, placebo-controlled trial was carried out between January 2001 and 2003.

Patients were recruited from the acute stroke assessment units of three hospitals in the northwest of England: the Royal Liverpool University Hospital; Arrowe Park Hospital, Wirral; and Whiston Hospital, St Helens. Patients were recruited to the trial within 24 h of admission to hospital following a first acute stroke. Those patients receiving antibiotic or steroid medication, including inhaled steroids, or having had a previous stroke were excluded from the trial.

The study was approved by the Local Research Ethics Committees, and the patients were required to give informed consent. For patients too ill to consent, next of kin were invited to give assent to allow these patients to be included in the trial.

All patients had a bedside swallowing assessment performed either by the previously training project research nurse or by a speech and language therapist using Smithard’s water swallow method, allowing patients to be subdivided into two groups—safe swallow and unsafe swallow [21].

Patients were randomised to receive either SDD gel or placebo. The orabase contained 2% (w/v) colistin, 2% (w/v) polymyxin E and 2% (w/v) amphotericin B. A 500 mg dose of gel or placebo was prescribed to be applied topically to the mucous membranes of the mouth four times daily. Application of the gel was performed either by a nurse using a gloved finger or spatula or by the patient with a clean finger. Treatment was continued for 3 weeks for patients with unsafe swallow and for 2 weeks for those with safe swallow. Randomisation was carried out using computer-generated random numbers by the research pharmacist at the Royal Liverpool University Hospital, from where supplies of SDD gel were distributed to the participating centres.

Oral swabs were obtained from patients on recruitment to the trial less than 24 h after admission and thereafter on each Monday, Wednesday and Friday until nine swabs had been obtained. A dry sterile swab (Medical Wire & Equipment, Corsham, Wiltshire, UK) was passed around the left and right upper and lower buccal sulci, over the hard palate, then over the tongue, and swabs were processed qualitatively and semi-quantitatively.

Each swab was inoculated onto solid culture media in the following order: 5% w/v horse blood agar; MacConkey agar; Sabouraud’s yeast morphology agar; kanamycin–aesculin azide agar (Oxoid, Basingstoke, Hampshire, UK). The tip of each swab was broken off into a 3 ml bottle of brain–heart infusion broth. These were incubated at 37°C for 24 h and then examined visually. Commercial kits API20E and API20NE (Biomerieux, UK) were used to identify Gram-negative micro-organisms. Colonisation was defined as the finding of isolated AGNB in the mouth on one occasion. Carriage was defined as the presence of the same organism on two or more consecutive samples from the same patient.

Barthel Index [22] and Scandinavian Stroke Scale [23] were performed on admission to hospital and on days 8 and 15 of hospital stay. The Barthel Index prior to stroke was estimated by questioning the patient and/or the relatives about the pre-stroke level of functioning.

In addition to data about medical history and concurrent illnesses, clinical data were obtained regarding episodes of septicaemia and/or respiratory tract infections during hospital stay. Pyrexia was defined as a peripheral temperature of 38°C or above, as recorded on the patient’s temperature chart, and the duration in days of any pyrexial episode was recorded. For the purpose of this study, clinical signs and symptoms of pneumonia as recorded in the case notes were accepted as evidence of probable pneumonia. This included comments made about X-ray changes, diagnosis of pneumonia, chest infection or lower respiratory tract infection being recorded in the notes as well as positive sputum culture reports. Septicaemia was defined as culture of one or more pathogenic organisms from the blood. Any antibiotics prescribed including the duration of treatment and route of administration were noted.


   Results
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 Abstract
 Introduction
 Methods
 Results
Discussion
 Key points
 Source of funding
 References
 
Combined data from patients from the three participating centres are presented. Table 1 summarises the demographic characteristics of the active and placebo groups for each of the hospitals and illustrates that they were not significantly different.


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  		Table 1.. Summary of demographic data

 

Dysphagia
Fifty-eight patients (29%) had dysphagia on admission to hospital, and the mean duration was 6 days, with 20 patients still dysphagic at day 8 and 12 at day 15.

Ten patients (17% of those with initial dysphagia) continued to have problems with swallow for the 3 weeks, and dysphagia resolved in all surviving patients by 12 weeks.

Micro-organisms and effects of SDD
We found AGNB to be present in the mouths of 11 patients on their first swab following admission to hospital: seven in the treatment group and four in the placebo group. AGNB were nosocomially acquired by 14 treatment and 23 placebo group patients. A total of 6 treatments and 11 placebo patients were colonised by AGNB. No significant differences were seen between the two groups.

Table 2 lists the micro-organisms cultured from oral swabs, and Figure 1 shows the number of positive isolates per time period for the treatment and placebo groups. In the treatment group, the number of positive samples peaks by the third sample and then falls during gel use, rising again in the third week when patients with a normal swallow discontinued the gel. In the placebo group, there was a marked rise in the number of positive samples, particularly at swabs 4 and 7. The numbers of positive samples were greater at the end of the sample period than at the beginning, in contrast to the treatment group (Table 3).


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  		Table 2.. Identity and frequency of isolation of aerobic Gram-negative bacteria

 


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  		Figure 1.. AGNB isolated from each swab.

 

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  		Table 3.. Pattern of AGNB isolation

 

Of the 58 patients with an abnormal swallow on admission, 13 were found to have AGNB present in their mouths at some time during the study. Of these 13, 9 were in the placebo group and only 4 in the treatment group. In the treatment group, two of the four patients had AGNB isolated from the first swab, and the remaining two acquiring AGNB during their hospital stay. In the placebo group, three of the nine had AGNB isolated from the first swab, and the remaining six acquired the AGNB during hospitalisation.

Five of the 58 patients (8.6%) with an abnormal swallow were found on initial swabs to have AGNB in their oral cavity. In contrast, six of 145 (4.1%) patients with a normal swallow were found to have organisms present in the initial swab (P = 0.2024, chi-squared).

AGNB were more likely to be isolated from the placebo group patients during weeks 2 and 3 of treatment (P = 0.034, chi-squared).

Clinical outcomes
Fourteen patients developed an infection during the study period: 10 occurred in the placebo group and 4 in the treatment group. Seven of the eight cases of pneumonia occurred in patients with abnormal swallow, and seven patients developed their infection during the first 2 weeks after stroke.

Twenty patients died whilst still inpatients (9 in active and 11 in placebo group), and three died within 3 months of discharge from hospital. Three inpatient deaths were attributed to pneumonia—all in the placebo group and with dysphagia. Figure 2 summarises these findings.



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  		Figure 2.. Clinical outcomes for the treatment and placebo groups.

 


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
Key points
 Source of funding
 References
 
This study has confirmed that acute stroke patients are prone to both isolation and carriage of AGNB. These potentially pathogenic micro-organisms are carried on admission to hospital by a proportion of stroke patients, whilst others acquire them nosocomially. The micro-organisms isolated from the patients in the study are those implicated in aspiration pneumonia. Eleven patients (5.4%) in this study were found to have AGNB on their first swab. Within the 100 patients in the placebo group, 27 (27%) were found at sometime during the first 3 weeks of hospitalisation to have either isolation or carriage of AGNB, being similar to the 34% carriage rates previously described by our group [13].

We found 29% of our patients to have dysphagia on admission to hospital, which is lower than our previous findings but consistent with the 27% patients still at risk at the end of week 1, described by Smithard et al. [7]. Our cohort, we believe, is fitter than that described by others [7, 12]. Our mortality rates were lower, and this may be because assent and consent are more difficult to obtain in interventional trials than in purely observational studies. When considering patients with an abnormal swallow, they were twice as likely to have organisms present in the first swab than those with a normal swallow, although this did not reach statistical significance. In the placebo group, a further six patients were found to have AGNB during the 3 weeks of study, although only a further two patients in the active group developed positive cultures for AGNB during their subsequent stay, thus suggesting that the AGNB are quick to colonise the oral cavity, and this occurs in the first hours after a stroke especially in patients with abnormal swallow.

The study has confirmed that SDD can eradicate AGNB from the oral cavity of stroke patients. Patients with normal swallow received the gel for 2 weeks, and therefore acquisition of AGNB in week 3 is not entirely unexpected. The most striking difference in AGNB isolation was seen between weeks 2 and 3 in those with a normal versus an abnormal swallow.

Escherichia coli were isolated in 24 different swabs, and Enterobacter species were isolated in 36 different swabs, in keeping with previous studies [13]. The SDD gel appeared to remove and prevent isolation of the following organisms: Chryseomonas luteola, Citrobacter freundii, Citrobacter koseri, Hafnia alvei and Serratia liquefaciens, which were found only in the placebo group. Amongst the treatment group, Klebsiella oxytoca, Klebsiella pneumoniae, Serratia marcescens and E. coli were found on initial swabs but not after the introduction of the SDD gel and therefore appeared to be removed by the gel.

We have shown that SDD reduces the incidence of aspiration pneumonia among acute stroke patients. In our study, pneumonia was uncommon, although there was a statistically significant difference in its incidence between those patients who received SDD gel and those who did not. Of the eight cases of pneumonia diagnosed during the study, seven occurred in patients with abnormal swallow. Three patients were deemed to have died as a result of pneumonia, and all had dysphagia on admission. It may be concluded from our study that the presence of an abnormal swallow and AGNB increased the risk of death and that SDD was efficacious in some patients. However, its use in all patients following stroke cannot be recommended, and organisms were able to colonise the oral cavity after discontinuation of the gel. It might therefore be suggested that SDD gel plays a vital role in patients with an abnormal swallow, and further studies should target this group continuing SDD gel for the duration of the dysphagia, not for an empirical predetermined duration.

Future investigation should also address the mechanisms by which AGNB are able to colonise the oral cavity and why stroke patients are particularly prone to such colonisation.


   Key points
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Key points
Source of funding
 References
 

  • Aspiration pneumonia is a common complication of acute stroke.
  • The presence of gram-negative bacilli in the mouths of stroke patients may predispose to aspiration pneumonia.
  • High levels of carriage and colonisation by AGNB are found in patients in the first 3 weeks following an acute stroke.
  • SDD reduces the presence of organisms and documented episodes of pneumonia in patients following acute stroke.


   Source of funding
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Key points
 Source of funding
References
 
This project was funded by the Northwest Zonal Research and Development. AEW was employed as a research nurse by this funding body.


   References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 Key points
 Source of funding
 References
 

  1. Office for National Statistics. Mortality statistics: cause. Review of the Registrar General on deaths by cause, sex and age, in England & Wales, 1999. Series DH2 No. 26. 2000. London: The Stationery Office.
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  3. Secretary of State for Health. The health of the nation: a strategy for health in England 1992. London: HMSO.
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  5. Secretary of State for Health. Saving lives: our healthier nation. Cm. 4386 1999. London: The Stationery Office.
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  7. Smithard DG, O’Neill PA, England RE et al. The natural history of dysphagia following a stroke. Dysphagia 1997; 12: 188–93.[CrossRef][ISI][Medline]
  8. Barer DH. The natural history and functional consequences of dysphagia after hemispheric stroke. J Neurol Neurosurg Psychiatry 1989; 52: 236–41.[Abstract]
  9. Daniels SK, Ballo LA, Mahoney MC, Foundas AL. Clinical predictors of dysphagia and aspiration risk: outcome measures in acute stroke patients. Arch Phys Med Rehabil 2000; 81: 1030–3.[CrossRef][ISI][Medline]
  10. Johnson JL, Hirsch CS. Aspiration pneumonia. Recognising and managing a potentially growing disorder. Postgrad Med 2003; 113: 99–102.[CrossRef][Medline]
  11. Marik PE. Aspiration pneumonitis and aspiration pneumonia. N Engl J Med 2001; 344: 665–71.[Free Full Text]
  12. Preston AJ, Gosney MA, Noon S, Martin MV. Oral flora of elderly patients following acute medical admission. Gerontology 1999; 45: 49–52.[CrossRef][ISI][Medline]
  13. Millns B, Gosney M, Jack CI, Martin MV, Wright AE. Acute stroke predisposes to oral Gram-negative bacilli – a cause of aspiration pneumonia? Gerontology 2003; 49: 173–6.[CrossRef][ISI][Medline]
  14. Teasell RW, McRae M, Marchuk Y, Finestone HM. Pneumonia associated with aspiration following stroke. Arch Phys Med Rehabil 1996; 77: 707–9.[CrossRef][ISI][Medline]
  15. van Saene HK, Stoutenbeek CP, Torres A. The abnormal oropharyngeal carrier state: symptom or disease? Respir Med 1992; 86: 183–6.[ISI][Medline]
  16. Marsh P, Martin HV. Oral Microbiology, 4th edition. Wright: Oxford, 1999.
  17. Baltimore RS, Duncan RL, Shapiro ED, Edberg SC. Epidemiology of pharyngeal colonisation of infants with aerobic gram-negative rod bacteria. J Clin Microbiol 1981; 14: 51–62.
  18. Marsh PD, Percival RS, Challacombe SJ. The influence of denture-wearing and age on the oral microflora. J Dent Res 1992; 71: 1374–81.[Abstract/Free Full Text]
  19. Mackowiak PA, Martin RM, Jones SR, Smith JW. Pharyngeal colonisation by gram-negative bacilli in aspiration-prone persons. Arch Intern Med 1978; 138: 1224–7.[Abstract]
  20. Sleijfer DT, Mulder NH, Vries-Hospers HG et al. Infection prevention in granulocytopenic patients by selective decontamination of the digestive tract. Eur J Cancer 1980; 16: 859–69.[Medline]
  21. Smithard DG. Dysphagia assessment after acute stroke. Hosp Update 1995: 555–61.
  22. Mahoney FI, Barthel DW. Functional evaluation: the Barthel Index. Md State Med J 1965; 14: 61–5.[Medline]
  23. Lindentrom E, Boysen G, Christiansen LW, Rogri Hansen BA, Neilsen PW. Reliability of Scandinavian Neurological Stroke Scale. Cerebrovasc Dis 1991; 1: 103–7.[CrossRef][ISI]
Received June 14, 2005; accepted in revised form September 20, 2005.


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