Introduction
In this paper, the article entitled “Lactobacilli and bifidobacteria in the prevention of Antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomized, double-blind, placebo-controlled, multicentre trial” by Allen, et al., (2013) will be critically reviewed. The article investigates about Antibiotic-associated diarrhoea (AAD) which occurs more often in older patients who are 65 and above and are treated with antibiotics that provide immunity against a wide range of bacterial diseases. Clostridium difficile is a dangerous bacteria which can cause AAD, and it can be very harmful to the patient’s health. The researchers “did a multicentre, randomized, double-blind, placebo-controlled, pragmatic, efficacy trial of inpatients aged 65 years and some much older, and they administered them with some oral antibiotics and some parental antibiotics”. The study is being conducted because some studies did not provide sufficient and reliable accurate data and was funded by the NIHR Health Technology Assessment programme. Patients are already having antibiotic treatment within previous two months, probiotic use within the last seven days (medicinal purposes), Immunodeficiency, chronic GI disease, and diarrhoea (acute or chronic) cannot be included in the study.
Evaluation of the Introduction Section
Administration of a high dose of lactobacilli and bifidobacterium did not show the effect of Prevention of AAD in the trial of nearly 3,000 older inpatients. Other side effects are diarrhoea severity, the frequency of abdominal symptoms, the length of hospital stay, and quality of life showed no evidence of a beneficial effect attributable to the microbial preparation.
Aims or hypotheses
The aim of the study was to admit people in the hospital and treat them with the antibiotics and the administration of multi-strain probiotic that will decrease the number of AAD. The antibiotic which is related to physical health associated with the diarrhoea is very critical and serious issue which affects the health. The solutions which are available to prevent Clostridium difficile diarrhoea were very expensive and interrupted the clinical health care. The study is aimed to test the administration of a probiotic having multi strains of lactobacilli and bifidobacteria two strains from each, alongside antibiotic treatment prevents antibiotic-related diarrhoea. It was not much precise about intervention and outcomes.
Evaluation of the Methods Section
The participants were the patients who administered with one or more oral antibiotics or parenteral antibiotics. The inclusion criteria were the patients aged more than 65 years who were admitted to the hospital, consultant approval to invite patient to join the study, and the Clostridium difficile in past three months. The exclusion criteria were existing diarrhea, immuno-compromisation requiring isolation or barrier nursing, illness requiring high dependency care or intensive care, prosthetic heart valve, Clostridium difficile infection in previous three months, and inflammatory bowel disease needing specific treatment in previous twelve months. Exclusion criteria also include suspected acute pancreatitis, known abnormality of disease of mesenteric vessels or coeliac axis, receiving jejunal feeds, previous adverse reaction to probiotics, unwilling to discontinue current probiotic regime, nil by mouth patients, severely ill patients, and the patients not expected to survive the study time frame. If the sampling mode was appropriate, this could become better and easy. The medical and surgical wards of five hospitals were used in this trial.
Apparatus
It was a “multicentre, randomized, double-blind, placebo-controlled, pragmatic, efficacy trial study” . There was a scheme which was generated through computers, it was randomized and was used to distribute the participants to get a preparation of multi-strain lactobacilli and bifidobacteria, in 21 days at least one, with 60 billion organisms, or a similar placebo. The study included hospital staff, patients, specimen, instruments, equipment, data analysts and other associated things which were masked properly. The questions on the validity and reliability of the instruments are possible.
Placebo Study
It was a placebo-controlled study, the patients in the placebo-controlled study were randomly selected. Other groups should also be considered for better and accurate results.
The patients were randomly selected in the groups. Some characteristics distinguished between the two groups at the time of selection. The assigned sequence was generated by the independent statistician who had no contact with the members of different groups until the data and research had been completed and locked.
Treatment Parameters
Treatment is done with the most common indication like respiratory, thoracic, and meditational disorders. Treatment parameters in this study need more genuine description. In this study, prolonged follow-up for participants on the long-term use of antibiotics was not viable, and follow-up was discontinued at eight weeks after recruitment. Gastrointestinal symptoms, adverse events, Changes to antibiotic treatment, the occurrence of diarrhoea, and compliance with the trial interventions were recorded on standard forms.
A lyophilized powder in a vegetarian capsule (one daily) containing six x1010 live bacteria was given. Lactobacillus acidophilus two strains including “(CUL60, National Collection of Industrial, Food and Marine Bacteria {NCIMB} 30157; and CUL21, NCIMB 30156) and two strains of Bifidobacterium (Bifidobacterium bifid CUL20, NCIMB 30153; and Bifidobacterium lactic CUL34, NCIMB 30172” (Allen, et al., 2013).
Rosenthal and Hawthorn effects
Hawthorn effects are independent safety monitors, and Rosenthal effect refers to higher expectations which direct towards an increase in the performance.
Results Section
The study included 2941 (98.7%) participants. From the study, it could be identified that both study groups had common risk factors for AAD. Furthermore, the study indicated that the frequency of AAD in placebo groups Clostridium difficile disease was not a common reason of AAD. It occurred in 1.0204 participants in the other group while in the case of placebo group it was 0.963 “(RR 0.71; 95% CI 0.34 to 1.47; p = 0.35)” (Allen, et al., 2013). Gastrointestinal symptoms, duration, and severity of diarrhoea, severe side effects and quality of life measures was also found in the placebo group.
Discussion
Clostridium difficile is a dangerous bacteria which can cause Antibiotic-associated diarrhea AAD, and it can be very harmful to the patient’s health. Clostridium difficile is a bacteria which is an opportunistic organism that is known for causing intestinal infection in patients. Since antibiotics disturb the natural intestinal flora, leading to susceptibility to infection from Clostridium difficile certain studies are conduct to prevent AAD in patients.
The research done by the National Institute for Health Research, UK did not prove complete prevention from the AAD through administering preparation of two antibiotics which are lactobacilli and bifidobacterium. It was a study that included only 3,000 patients of old age, but to prove a study worldwide the ratio of 3,000 seems so less. People and groups choose to try this study should me more in order to present a strong and authentic outcome. The people in the grouping should be from different tribes and countries, just to concern the environmental factors too. The analysis was done after a study of secondary outcomes did not show many beneficial results of the preparation of those antibiotics. The secondary outcomes that were not affected by the administration of this preparation of antibiotics include frequency of abdominal symptoms, the length of hospital stay, diarrhea severity, and quality of life.
The study was done by the busiest hospital the National Institute for Health Research is the largest study done concerning this topic of AAD. However, they had several weaknesses in their study which they tried to minimize through decreasing and controlling the inclusion and exclusion criteria. In their study they predisposed to diarrhea and those who might be at specific risk from bacterial supplements, they enlisted fewer than one in five eligible patients. The patients who refused to participate in this study had different reasons for someone who already was on other preparation of medicine, and some were just unwilling to be a part of this trial. The attitude of the participant was the main difficulty while conducting the trial especially while dealing with the older patients. The variety of the ethnicity was very low in this study only the local patients who were more than 65 years older were seen. In this study the point that lactic acid is effective for older patients against AAD is proven wrong as the production of lactic acid was not effective to prevent AAD. To find a cure and prevention for a disease like AAD, it is very important to understand its pathophysiology first then switch to further studied to prevent it. A lot of antibiotics cause diarrhea and the cause of some are still unknown, and this effects and interrupts any treatment in the normal flora, which is always different in every individual of any age. And it is also affected by any chronic disease, age factor, weakness, care methods, residence, and diet. It needs to be investigated in depth that certain strains of microbes show certain anti-diarrheal functions. The researchers in this failed to get stool samples of most of the patients as the period of AAD was very short in some of the patients. Problems like this should be solved by some measures to overcome such problems should be made. They were unable to take stool samples of some patients that mean they had a very low number of sample to prove their study; this clearly means that the number of samples was less than the number of patents in the end. The result of this study does not give evidence to take that preparation of antibiotics on a routine basis to avoid AAD. It is recommended to conduct furthers studies after studying the pathophysiological of the disease carefully and use specific microbes that act against a specific problem in a specific group of people. According to the study after administration of probiotic for 21 days the occurrence of AAD decreased to 73% it means if the collection of the sample were monitored more correctly the result that must come more specifically and the decreased amount of AAD would be more than 27%. According to the study, the preparation of the antibiotic contained an approximately level of live probiotic (at least 1·62×10¹⁰). If a recovery period was used as part of the enumeration method, then the cells injured could have made up a major segment of the probiotic, these injured cells might not survive much. And it can be said that the mixture of strain was not correct in this study. So until now this study cannot be claimed as a perfect study to prevent Antibiotic-associated diarrhea AAD from Clostridium difficile through the combination of antibiotic, it needs to get rid of all its weaknesses and give out a perfect outcome which can help patients around the globe. And that can help people of any age ground, country or cast to cure AAD with proper dose and combination of antibiotics. So it needs further evaluation and research on bigger groups of people.
Conclusion
The practical study does not provide statistical evidence to support recommendations for the use of microbial preparations for the prevention of AAD. More studies should be conducted when there is the availability of supporting evidence that is one or more specific microbes act against identified underlying pathophysiological mechanisms for AAD.
The overall outcomes include baseline characteristics similar to both groups, AAD (including Clostridium difficile) occurred in 10.6% of participants (n=312) with similar frequency in both groups. A small but significant difference was seen in the probiotic group with an increase inflatus and having a nasogastric tube in situ, bloating was more common in patients in the probiotic group with Clostridium difficile infection the microbial preparation of lactobacilli and bifidobacterium did not prevent AAD in this trial.
References
Allen, S. J., Wareham, K., Wang, D., Bradley, C., Hutchings, H., Harris, W., et al. (2013). Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. The Lancet , 382 (9900), 1249-1257.
