Probiotics for Reduction of Infections With Clostridium Difficile in Critically Ill Patients
Probiotics for Reduction of Infections With Clostridium Difficile in Critically Ill Patients
Symptoms of Clostridium difficile infection is almost always induced as a complication to the
 use of antibiotics. Most ICU patients are given antibiotics.

 Probiotics has the ability to improve conditions in the gut and it has been shown in some
 smaller studies that overgrowth of C. difficile can be reduced or prevented.

 In this study the intention is to show with sufficient statistical power that a mixture of
 two otherwise well studied probiotic strains reduces or prevents the incidence of emerging
 colonisation with C. difficile in critical ill patients on antibiotics.

 Half of the patients will be given a mixture of Lactobacillus plantarum 299 and Lactobacillus
 plantarum 299v twice daily and the rest a placebo mixture.

 Rectal swabs or faeces will be analysed for C.difficile and its toxins and the incidence of
 new cases will be compared for the two groups.

 White blood cells (WBC´s), C reactive protein (CRP), lactate, urea, and creatinine will be
 followed daily as well as antibiotics, corticosteroids and all acid reducing medication.

 Nutrition, enteral and total, and bowel habits will be recorded.
Infections with Clostridium difficile is considered to be the most frequent health care
 associated bacterial infection. Almost all cases are connected to the use of antibiotics.

 The spectra of symptoms of infection reaches from loose stools to sepsis and death. It is
 estimated that about 5% of the population are carriers without symptoms.

 Elderly people are more likely to be diagnosed with C. difficile infections and as about 50 %
 of ICU admissions (at least in Sweden) are patients aged 64 years or older C. difficile is
 also an ICU issue.

 Probiotic bacteria given to antibiotic treated patients results in fever cases of infection
 with C. difficile as we and others have shown in some small studies. Due to a low statistical
 power in our former study this multicentre study is calculated to be large enough to fulfil
 statistical requirements.

 Adult patients with an expected length of stay in intensive care for three days or more can
 be included.

 Primary objective is to find emerging cases of colonisation with C. difficile and consequent
 symptoms of infection such as diarrhoea.

 Cultures and toxin analyses will be taken at inclusion and every second day till day 13 and
 then every third or fourth day depending on length of ICU stay. Positive cases will be given
 antibiotics according to normal routines.

 No other cultures are collected per protocol but all cultures will be recorded and results
 will be analysed in order to find any connection between treatment and reduction of secondary
 infections.

 In our earlier small study we found an improved and normalised gut barrier function for those
 patients that were given probiotic bacteria compared to a worsened, scattered pattern for the
 placebo group. This is probably why we found that inflammatory parameters improved for the
 probiotics group while those parameters remained elevated for the control patients. The same
 goes for creatinine, urea and lactate. This is why we will record those parameters together
 with blood gas analyses in this expanded study.

 Antibiotics and medication with corticosteroids, proton pump inhibitors or other acid
 reducing preparations, All nutritive prescriptions (enteral formulas and IV solutions as well
 as medical preparations containing glucose or fat) will be recorded and compared to actually
 given nutrients.

 Bowel movements frequency and consistency will be recorded and compared between groups.
Inclusion Criteria:

 -  Anticipated need for intensive care 3 days or longer

 -  Patients condition allowing enteral nutrition to be started within 24 h from ICU
 admission

 -  Antibiotics on-going or planned

 Exclusion Criteria:

 -  Known positive test for Clostridium difficile within the last week

 -  Known ulcers in the mouth, oropharynx, esophagus and stomach

 -  Known immune deficiencies

 -  Enteral nutrition contra indicated

 -  Pancreatitis as admission diagnosis at the hospital or at the ICU

 -  ICU admission earlier during this period of illness Patient being moribund