Joy Cleghorn, ICSSA treasurer, FIDSSA Nursing representative & National Infection Prevention and Control Risk Manager Life Healthcare
The following case scenario serves to introduce the topic of the testing, treatment and prevention and control required for Clostridium difficile Infection (CDI)
11 patients in a long-term care facility were reported with CDI over a 3 month period. All patients were appropriately treated and of these, 2 of the patients experienced recurrent CDI. The purpose of this document is to discuss the implementation of more stringent infection prevention and control measures together with increased environmental cleaning, based on literature research and evaluation of evidence-based practice.
Question 1: What is CDI
Answer to Q1
Clostridium. difficile has two forms, an active, infectious form that cannot survive in the environment for prolonged periods, and a non-active spore form that can survive in the environment for prolonged periods. Although these spores cannot cause infection directly, when they are ingested they transform into the active, infectious form and produce toxins.
Clostridium difficile can cause Clostridium difficile Infection (CDI) and is also referred to as C. difficile related colitis, formally known as CDAD (Clostridium difficile Associated Diarrhoea).
Clostridium difficile spores lie dormant inside the colon until a person takes antibiotics. The antibiotic disrupts the other bacteria that live in the colon and normally keep C difficile ‘in check’. When the normal balance of gut flora is disturbed, overgrowth of the organism can cause an acute inflammatory diarrhoea due to the production of toxins A and B. Disease can range from mild to severe and is sometimes fatal.
Question 2: Define diarrhoea with regards to Clostridium difficile
Answer to Q2
Clostridium difficile related diarrhoea is diarrhoea in the presence of a positive test for Clostridium difficile typically a loose watery stool that conforms to the shape of a container. These bowel actions are not usual for the specific patient and there is no other anticipated cause for diarrhoea e.g. the use of laxatives. These bowel actions can be voluminous and, less commonly, bloody (< 5%).
Severity of CDI is defined by the presence of WBC >15 x109/L, rising creatinine and/or signs and symptoms of colitis. The number of stools per day is not an indicator of severity. The most consistent marker of severity is raised WBC count.
Question 3: Testing for Clostridium difficile
Answer to Q3
Testing should only be done when there is an unformed diarrhoeal stool present, and the patient has been in hospital for at least 2-3 days, or has been in a health care facility recently. Patients who are admitted to hospital with a history of diarrhoea, but no risk factors for CDI should rather have stool examined for alternative pathogens if clinically indicated (viruses, parasites, Salmonella etc ).
In the past, diagnosis was usually done by detecting the presence of the toxin in stool samples, using either cell cytotoxicity assays (technically difficult, and not generally offered) or by commercial antigen detection tests such as lateral flow assays (much more user friendly). A number of assays exist to detect toxin, but suffer from poor sensitivity of 40-60% and specificity of most (if not all) of these tests. More recently a variety of molecular based tests have been made available, which seem to be far more reliable. The disadvantage of the molecular tests (certainly in the local context) is the often high price of the tests.
Re-testing for CDI once diarrhoea has subsided is not recommended, nor is testing of asymptomatic patients.
Question 4: What infection control measures are recommended to prevent spread of CDI?
Answer to Q4
The importance of good hand hygiene must be emphasized with all health care workers, patients and visitors. The use of a 4% chlorhexidine liquid soap and water has been documented as effective. Alcohol hand rub does not kill Clostridium difficile spores.
Isolation in a single room using contact precautions, with a dedicated commode or toilet is ideal. If this is not possible, cohort patients and ensures each patient has a dedicated commode.
Personal protective equipment
All health care workers and visitors must don gowns and gloves prior to entering the isolation area and gloves must be changed and hands washed after every contact.
Clean and disinfect the area using a hypochlorite at 1000ppm/available chlorine. High touch areas must be cleaned daily and the room must be terminally disinfected when the patient is discharged.
Use dedicated equipment e.g. blood pressure machines and cuffs, thermometers, stethoscopes etc.
Equipment must be cleaned with the hypochlorite solution or an acceptable sporicidal disinfectant wipe depending on equipment and sensitivity of material.
Discontinuation of any antibiotic that may be causing CDI is a key part of management of CDI. If the offending antibiotic is continued, time to resolution of diarrhoea is longer and the success rate of treatment of CDI is markedly reduced. Restricted or judicious antibiotic use will also reduce the incidence of Clostridium difficile infections.
Question 5: Treatment
Answer to Q5
There are currently 3 drugs internationally licenced for treatment of CDI; metronidazole, vancomycin and fidaxomicin. The action of metronidazole relies on re-secretion through an inflammed colon following absorption in the proximal gastrointestinal tract. The degree of inflammation determines the concentration of metronidazole available, which directly impacts on cure rates.
Answer to Q5
Pooled data from a multicentre randomised control trial of metronidazole vs vancomycin showed a clinical success rate of 72.7% for metronidazole compared to 81.1% for vancomycin (OR 1.68 95%CI 1.114-2.537). Approximately 25% of first cases of CDI will relapse after treatment, and of this group, 45-65% will have a further relapse (see below)
Answer to Q5
Most international guidelines advise metronidazole 400 mg orally 3 times per day for 10-14 days as first line treatment for mild to moderate CDI. Vancomycin 125 mg orally 4 times per day for 10-14 days is the drug of choice for severe CDI. Diarrhoea should resolve within 1-2 weeks and symptoms not improving or worsening should not normally be deemed a treatment failure until after 7 days. However, any evidence of developing severe CDI, metronidazole should be switched to vancomycin. If severe CDI fails to improve or worsens, intravenous metronidazole can be added to vancomycin. In countries where fidaxomicin is licenced, this would be an alternative. Early consultation with surgical colleagues is critical.
Answer to Q5
Trials of fidaxomicin, a novel macrocyclic antibiotic have shown cure rates of 88-92% at 30-day follow-up, i.e. non-inferiority compared to vancomycin, but with significantly reduced relapse rates of only 12-15%. Fidaxomicin is suggested as the treatment of choice for recurrent Clostridium difficile infection in new guidelines from Public Health England. The drug is prohibitively expensive for use in resource-limited settings. The benefit of fidaxomicin over vancomycin is not apparent against the CD027 strain.
Answer to Q5
Whilst probiotics have not been proven to be efficacious in the treatment of CDI, a recent landmark RCT of the ultimate probiotic combination, faecal transplantation, which was published in the New England Journal of Medicine, was stopped prematurely by the Drug and Safety Monitoring Board for the study. A total of 81.3% of patients were cured without relapse following faecal transplantation compared to 30.8% for those treated with vancomycin or 23.1% for those treated with vancomycin with bowel lavage, basically a sham procedure. Hence, faecal transplantation presents a treatment option for patients with multiple recurrences of CDI.
Question 6: Why are there relapses of CDI
Answer to Q6
Relapses typically occur 3-10 days after metronidazole or vancomycin is stopped. The main risk factors for recurrence are continuation of antibiotics and impaired humoral immunity. Other factors include previous recurrence, strain type, age and co-morbidity. Relapse occurs due to surviving spores, which transform into active bacterial forms, multiply and produce toxins again.
Challenges to the diagnosis and treatment of C difficile infection remain and the injudicious use of antibiotics continues to put patients at risk of this serious healthcare associated infection. Implementation of more stringent prevention strategies and infection-control practices are key to tackling this serious infection.
The author has no conflicts of interest to disclose.
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