Probiotics for Antibiotic-Associated Diarrhoea
Older people living in care homes are generally more frail, and have a higher risk of having infections than other groups. Taking antibiotics can be associated with a number of health problems, including diarrhoea, and developing antibiotic resistance which makes it much harder to treat infections (in both the person who was treated and others who may need treatment) later on. The PAAD Study was a two-stage study, funded by the National Institute for Health Research.
Aims of the PAAD Study
Full details of the study can be found here.
The first stage aimed to explore how often care home residents are prescribed antibiotics, and how often they develop diarrhoea and Clostridium difficile infection (commonly known as C. difficile) as a result, and also to look at how a randomised controlled trial (RCT) of probiotics (given alongside any antibiotics) to prevent antibiotic-associated diarrhoea could be carried out.
Stage 2 was to be a trial of a probiotic preparation involving 400 care home residents who would be randomised to receive either the probiotic or an identical placebo preparation. However, the trial aspect did not go ahead due to a number of reasons. Some of the issues we encountered when setting up the second stage of the study, the randomised controlled trial, and our recommendations for future research practice have been published, and can be accessed here.
In order to record how many care home residents developed infections, were prescribed antibiotics, and developed diarrhoea, residents who took part in the study were monitored for 12 months. During this time any infections, antibiotic prescriptions, and episodes of diarrhoea were obtained from their care records, and they were asked to provide stool specimens at certain points. They (or their carers) were also asked to complete questionnaires that give an indication of their quality of life.
What did we find?
A total of 279 care home residents took part, from 11 care homes around the South East Wales area. We found that the number of antibiotics prescribed for care home residents is high – a resident could be expected to have just over two antibiotic prescriptions over a 1 year period. The most common infections treated with antibiotics were urinary tract infections followed by upper respiratory tract infections, and amoxicillin was the most commonly prescribed antibiotic. About half of all residents treated with antibiotics developed diarrhoea.
What are our recommendations for carrying out future studies in care homes?
Carrying out the study we found that approaching care homes to take part in the study takes more time in this setting comparted to other settings. It also generally takes longer to approach and recruit residents to take part, especially if they have impaired capacity and other people need to be involved in the decision about whether they should take part or not. We also found that it was difficult for busy care home staff to collect the study data, and it was difficult to obtain the stool samples needed for the study. We suggest that those carrying out similar clinical research in care homes may wish to consider*:
❖ Consulting an ‘expert’ with experience of working in a care home at the design stage of the study
❖ Allowing plenty of time to initially approach care homes, set up the sites, recruit residents and undertake the study
❖ Ensuring that processes are easy for staff to complete and where possible following their own processes, so as to not add to staff workload
❖ Embedding additional study staff or employing research nurses in the care homes to collect information from residents and carry out any sampling.
What did care home staff, residents, and relatives’ say about research in care homes?
We also explored, through interviews and focus groups with care home staff, residents, relatives and general practitioners, their views about any ethical and practical issues in conducting research in care homes, particularly a clinical trial in which residents would take part for a year. We found they were supportive of research being conducted in care home settings, and informed consent procedures would be broadly acceptable in any future trial of probiotics. The full recommendations for future research practice have been published, and can be accessed here.
The PRINCESS Study (Probiotics to Reduce Infections in Care home residents)
Infections in care home residents are more likely to be severe, recurrent and often require a stay in hospital and care home residents are frequently prescribed antibiotics, increasing the likelihood of antibiotic resistant infections (such as MRSA). Infections are a problem for care home residents because of weakened immunity, multiple illnesses and living near others. The Centre for Trials Research at Cardiff University is running the PRINCESS study funded by the National Institute for Health Research.
Aims of the study
This study aims to find out if people living in care homes who take probiotics (‘good bacteria’) each day have fewer infections and need antibiotic treatment less often. Probiotics are live bacteria and yeasts often described as 'good' or 'friendly' usually added to yoghurts or taken as food supplements. Existing research has shown that probiotics reduced antibiotic use and risk of respiratory infections in adults and may reduce antibiotic associated diarrhoea. Therefore, probiotics could benefit care home residents.
What will we do?
We aim to recruit 330 care home residents from approximately 20 care homes in England and Wales, and residents will be in the study for 12 months. This is to find out if a daily probiotic affects the need for antibiotic treatment for care home residents, how long any infections last, their immune response to the annual flu vaccine, and their general wellbeing. We ask residents to provide blood, stool, and saliva samples at certain points in the study, and complete questionnaires about their wellbeing and quality of life. This is a randomised controlled trial (RCT), so the care home residents taking part will receive either an active (probiotic), or a placebo capsule - to be taken once a day for 12 months. Capsules can be opened and sprinkled on food/drinks if needed. Neither the resident, care staff, nor the trial team know who has the active or placebo.
What have we learnt from setting-up a clinical trial with care homes?
The trial covered 12 months of follow up, daily administering the capsules, weekly collecting diary data e.g. any new infections and hospitalisations; and collecting data and samples at three and twelve months. We had to identify a Principal Investigator to take responsibility for the trial at that care home (care home manager, registered nurse at the care home, or a psychogeriatrician at the local NHS Trust). Care homes have a different skill mix of staff working with an active part in the trial administering the probiotic/placebo and collecting samples. We were supported by very experienced research nurses who get to know each care home and the residents very well and carry out as much of the research activity as possible. PRINCESS has ethical approval to include care home residents with, and without capacity (using a consultee to provide advice) to enter the trial. For care home residents without capacity we identify and contact relatives or friends to ask if they are willing to act as consultee, sometimes a lengthy process.
* Hood K, Nuttall J, Gillespie D, Shepherd V, Wood F, Duncan D, et al. Probiotics for Antibiotic-Associated Diarrhoea (PAAD): a prospective observational study of antibiotic-associated diarrhoea (including Clostridium difficile-associated diarrhoea) in care homes. Health Technol Assess 2014;18(63).
Vicky Shephard, NIHR Doctoral Research Fellow ShepherdVL1@cardiff.ac.uk
Trials Unit, Cardiff University http://www.cardiff.ac.uk/centre-for-trials-research/about-us
The National Institute for Health Research (NIHR) https://www.nihr.ac.uk/
PRINCESS study https://www.cardiff.ac.uk/centre-for-trials-research/research/themes/infections/princess-study