Avoid unnecessary and unnecessarily long courses of antimicrobial treatment.
Be active in taking samples if a patient has diarrhoea during or after antimicrobial treatment.
Patients with diarrhoea in hospitals and long-term care institutions are treated applying contact precautions.
The close surroundings of patients with diarrhoea should be cleaned with agents that are effective against bacterial spores.
When treating a patient with diarrhoea, the hands should be washed with water and soap before applying a disinfectant.
General remarks
Any antimicrobial drug may cause Clostridioides difficile enteritis but the risk varies between different drugs. The risk is highest in association with the use of cephalosporins, fluoroquinolones and clindamycin.
Clinical manifestations and diagnosis
Watery, sometimes bloody diarrhoea. Diarrhoea may be absent in the most severe disease forms due to paralytic ileus.
The diarrhoea begins after the start of antimicrobic therapy, sometimes already during the same day, sometimes only after weeks. In rare cases, C. difficile enteritis may appear without preceding antimicrobial treatment.
In C. difficile diarrhoea, the patient often has abdominal pain, abdominal cramps and fever.
The most severe forms of C. difficile infection, such as pseudomembranotic colitis or toxic megacolon, may be life-threatening.
ESR and serum CRP are increased. C. difficile infection often increases CRP by more than 100 units.
The diagnosis of C. difficile induced diarrhoea is based on the detection of the bacterium toxin from a stool specimen. Gene amplification assays are very sensitive and may show a positive result even without a clinical disease. Such a test should be carried out only in patients who are clinically suspected to have a C. difficile infection. Gene amplication assays should not be used for monitoring treatment response: the test may remain positive for a long time after a healed C. difficile infection.
Treatment
Mild diarrhoea, no fever
In mild diarrhoea associated with antimicrobial therapy, stopping the antimicrobial drug may be all that is needed.
At least if the diarrhoea is prolonged, test for C. difficile using a gene amplification assay.
Abdominal pain, profuse diarrhoea, bloody diarrhoea or fever
A clinical suspicion is a sufficient basis for starting the therapy, at least in patients with severe symptoms or fever. A gene amplification test is performed before starting the treatment or as soon as possible.
Concurrent use of metronidazole and warfarin should be avoided due to the risk of bleeding. Metronidazole may also cause neuropathy. Peroral vancomycin is not absorbed, which is why its adverse effects are minor. Vancomycin is, however, clearly more expensive than metronidazole.
Metronidazole should be switched to oral vancomycin if no treatment response is obtained within 3-4 days.
In severe disease (blood leucocytes > 15 x 109 , fever > 38°C or strong abdominal pain), medication is changed to vancomycin 125 mg × 4 p.o. for 10 days.
Choosing vancomycin in milder forms of the disease as well is backed up by age > 65 years, significant underlying diseases and immunodeficiency.
Fidaxomicin is also an effective drug, but its use is limited by its high price.
In complicated disease (sepsis, fever > 38.5°C, clinical picture or radiological findings suggesting severe form of disease) the treatment is started with a combination of oral vancomycin (125-250 mg × 4) and intravenous metronidazole (500 mg × 3). If sepsis is suspected, piperacillin/tazobactam may be added to the C. difficile treatment.
Fluid replacement is given according to the severity of diarrhoea and the patient's general condition.
Use of drugs that decrease intestinal motility (e.g. loperamide, opioids) should be avoided.
Recurrent C. difficile diarrhoea
The diarrhoea may relapse in as many as one out of four patients.
The first relapse is treated with oral vancomycin 125 mg × 4 for 10 days.
Should further relapses occur, a long oral vancomycin therapy (extended duration vancomycin, EDV), with slow tapering of the dosage or with pulsed dosing, is used.
Extended therapy (7 weeks) with taper regimen: starting dose is 125 mg 4 times daily p.o. for 1-2 weeks and thereafter
125 mg twice daily p.o. for 1 week
125 mg once daily p.o. for 1 week
125 mg every second or third day p.o. for 2-8 weeks
125 mg every third day p.o. for 2 weeks
Pulse regimen: 125 mg 4 times daily p.o. for 10 days, thereafter 125 mg every 3rd day for 3 weeks.
Fidaxomicin is an alternative, 200 mg twice daily p.o. for 10 days.
Faecal transplantation is an effective treatment for recurrent relapses. Faecal transplantation should be considered the latest when extended vancomycin therapy or therapy with pulsed dosing has failed. In faecal transplantation, bowel microbiota acquired from a donor is transplanted with the aim of correcting the disturbance in the intestinal microbiome that leads to recurrent C. difficile infections. For the time being, faecal transplantation is performed by colonoscopy.
A monoclonal antitoxin antibody, bezlotoxumab, is also available as a novelty, which in some patients may end the recurring cycle of infections. Its effectiveness is probably as good as that of faecal transplantation, but bezlotoxumab offers a potential therapeutic alternative for those to whom faecal transplantation cannot be done.
The settings in which bezlotoxumab is used are not yet completely established. The drug is expensive but competitive with faecal transplantation since a colonoscopy is not required. A specialist in infectious diseases or gastroenterology should be consulted about using bezlotoxumab.
Prevention
Avoid unnecessary use of antimicrobials.
Clostridioides difficile spreads through direct contact.
Good hand hygiene is the best way to prevent the infection from spreading from one patient to another.
When treating patients with C. difficile, a different hand hygiene practice is applied compared to ordinary situations.
The hands are disinfected before treating the patient and they are washed and disinfected after the treatment and when leaving the patient room.
Spores are resistant to alcohol-based hand rubs, and the staff in care institutions may thus easily transfer bacteria from one patient to another.
A patient with diarrhoea is treated applying contact precautions. Precautionary measures are continued until 2 days have passed since the last diarrhoea stools. Protective gloves are used when the patient or his/her immediate surroundings are touched. Furthermore, a single-use protective apron or coat is used in treatment situations involving close contact to the patient. Stethoscopes, thermometers and similar small instruments should not be shared between several patient rooms, and they are maintained after every treatment period.
Excretion stains on the surfaces are cleaned with appropriate measures.
The patient is primarily treated in a single room.
If there are not enough isolation beds, two patients with C. difficile may be placed in the same room (forming a cohort).
During an epidemic, cleaning of the facilities is intensified.
Control samples are not needed after the diarrhoea has resolved. Contact precautions may be discontinued 2 days after the diarrhoea has resolved. An employee in contact with patients who has contracted a C. difficile infection can return to work 2 days after the diarrhoea has resolved, as in any gastroenteritis with vomiting and/or diarrhoea.
The position of probiotics in the treatment and prevention of C. difficile is unclear. According to studies and meta-analyses, Lactobacillus rhamnosus GG and Saccharomyces boulardii may be beneficial in the prevention of diarrhoea associated with antimicrobials. The level of evidence, however, is not adequate to provide recommendations.
Use of probiotics in persons with immunodeficiencies entails risks.
References
Mattila E, Uusitalo-Seppälä R, Wuorela M et al. Fecal transplantation, through colonoscopy, is effective therapy for recurrent Clostridium difficile infection. Gastroenterology 2012;142(3):490-6. [PubMed]