Community Management of Clostridium difficile Infection (CDI)

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Download the complete Community Management of CDI Algorithm for printing:  Community CDI Algorithm (DPC Approved).pdf [pdf] 324KB

Abbreviations

BD – Twice daily, BP – Blood Pressure, CDI – Clostridium difficile Infection, CCM – Consultant Medical Microbiologist

CRP – C-Reactive Protein, FBC – Full Blood Count, FMT – Faecal Microbiota Transplant, H2RA – H2 Receptor Antagonist, QD – Once daily, PPI – Proton Pump Inhibitor, QDS – Four times daily, TDS – Three times daily, TPR Temperature, Pulse, Respiration, U&E – Urea and Creatinine, WCC – White Cell Count (total)

Disease Classification

Clostridium difficile causes a spectrum of disease, ranging from asymptomatic carriage to severe and life threatening illness. CDI can also lead to life-threatening complications such as severe swelling of the bowel from a build-up of gas (toxic megacolon).

Severity index

 

Symptoms of Clostridium difficile Infection (CDI) can include:

diarrhoea (types 5-7 Bristol Stool Chart)
temperature above 38ºC (100.4ºF)
painful abdominal cramps.
CDI should be considered in patients presenting with diarrhoea with no other obvious cause (e.g. history suspicious of food poisoning, viral gastroenteritis or foreign travel), particularly in the presence of the following risk factors:

  Risk factors for CDI

Asymptomatic carriage is seen in up to 3% of healthy adults, but may be as high as 20% in elderly patients in hospital1 and 50% in some long-term care facilities2. Over 80% of reported cases occur in people aged over 65 years2 It most commonly affects people who have been treated with antibiotics.

Spores of the Clostridium difficile bacteria can be passed out of the human body in faeces (stools) and can survive for many months, and sometimes years, on objects and surfaces. Latest evidence also suggests that symptomatic patients can also carry high levels of Clostridium difficile spores on the skin, making hand washing with soap and water (not alcohol gels) essential.

Prevention of CDI in the Community

Probiotics: There is currently conflicting evidence for the use of active culture yoghurts / probiotics to restore intestinal bacterial diversity but probiotics containing Saccharomyces boulardi or Lactobacillus species may help to prevent CDI relapse and could be worth pursuing in some patients.3 Care should be taken when administering live probiotics to those with severe immunocompromise. Patients should be advised to purchase probiotic products themselves.

PPI graph PPIGastric acid suppression: Gastric acid suppressing medications are shown to increase the risk of developing CDI and may contribute to re-infection. There is a clear dose response effect between the degree and type of acid suppression and CDI4-7:

No gastric acid suppression odds ratio (OR) 1
OR 1.53 (95% CI, 1.12-2.10) H2 Receptor Antagonist
OR 1.74 (95% CI, 1.39-2.18) daily PPI
OR 2.36 (95% CI, 1.79-3.11) more frequent PPI.
Reviewing the need for acid suppression and where possible stopping PPI’s (using a tapering regime with concomitant alginate cover for patients who have been receiving PPI’s for more than eight weeks) or switching to a H2 Receptor Antagonist or lower risk alternative is likely to be beneficial.

anti Antimicrobials: All non-CDI related antimicrobial treatment should be stopped in patients with CDI wherever possible. Exposure to any antimicrobial agent generally increases the risk of CDI and stopping concurrent antimicrobials may give intestinal bacterial flora the opportunity to repopulate4-8.

No antimicrobial therapy odds ratio (OR) 1Antimicrobial risk
All Antimicrobials OR 6.91 (95% CI 4.17-11.44)12,13
In community-associated cases, the following antimicrobials carry increased likelihood of CDI:

Clindamycin OR 16.80 (95% CI 7.48-37.76)8,12
Cephalosporins OR 5.68 (95% CI 2.12-15.23)8,12
Quinolones OR 5.50 (95% CI 4.26-7.11)8,12
Penicillins OR 2.71 (95% CI 1.75-4.21)8,12
Macrolides OR 2.65 (95% CI 1.92-2.43)8,12
Trimethoprim & Sulfonamides OR 1.81 (95% CI 1.34-2.43)8,12
Tetracyclines – no significant association seen

Diclofenac: has been linked with an increased risk of CDI. Where possible, consider stopping.9

Relapse Therapy:

Tapering vancomycin: Where the patient has already been treated with and failed to response to oral metronidazole or relapsed, use oral vancomycin 125mg QDS for 10-14 days. The use of tapering dose vancomycin may also be helpful10:

·      Week 1: 125mg QDS

·      Week 2: 125mg TDS

·      Week 3: 125mg BD

·      Week 4: 125mg OD

·      Week 5: 125mg alternate days

·      Week 6: 125mg every third day

Fidaxomicin: is a relatively new macrocylic antibiotic licenced for the treatment of moderate to severe CDI and has been shown to be non-inferior to vancomycin.10,11 There is evidence that it reduces the numbers of patients who relapse with CDI but there is limited data to support efficacy once the patient has had a number of relapses. In specific cases, where the patient i) is over 65 years of age, ii) has severe or fulminant illness and iii) needs concomitant antimicrobial treatment, it may be appropriate to use Fidaxomicin10,14,15. However, this treatment is comparatively expensive (£1,300 per course ex VAT) and should only be used on the advice of a consultant clinical microbiologist.

 

Faecal Microbiota transplant: For recurrent relapse, the most effective treatment may be a faecal transplant to replenish the patient’s intestinal flora. NICE support the use of faecal transplantation for the treatment of recurrent CDI (NICE IPG485 March 2014, https://www.nice.org.uk/guidance/ipg485 )16.

Faecal transplantation has a primary cure rate of 81% with an overall cure rate of 94% (compared with Vancomycin at 31%) and donor stools are currently available through Portsmouth Hospitals.

At the point of relapse, the patient should be started on vancomycin 125mg QDS to control their symptoms and referred for faecal transplantation.

Patients can receive this treatment as a day case using a donor sample available from a donor bank which has been fully screened for safety. The procedure involves the passing of a nasojejunal tube on the day, an x-ray to check placement and the infusion of the faecal transplant via the nasojejunal tube. Although this sounds unpleasant, patients tolerate the procedure well with good clinical effect.

 

1. Report to the Department of Health . National Clostridium difficile Standards Group, February 2003.

2. Riggs MM,  Sethi AK Zabarsky TF, et al. Asymptomatic Carriers Are a Potential Source for Transmission of Epidemic and Nonepidemic Clostridium difficile Strains among Long-Term Care Facility Residents: Clinical Infectious Diseases 2007; 45:992–8

3. Goldenberg JZ, Ma SS, Saxton JD, et al. Probiotics for the prevention of Clostridium difficile-associated diarrhoea in adults and children. Cochrane Database Syst Rev. 2013 May 31;5:CD006095. doi: 10.1002/14651858.CD006095.pub3.

4. Howell MD, Novack V, Grgurich P, et al D. Iatrogenic gastric acid suppression and the risk of nosocomial Clostridium difficile infection. Arch Intern Med 2010; 170: 784-90.

5. Dial S, Delaney JA, Barkun AN et al. Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile associated disease. Journal of the American Medical Association 2005; 294: 2989−95.

6. Dial S, Delaney JA, Schneider V and Suissa S. Proton pump inhibitor use and risk of community-acquired Clostridium difficile-associated disease defined by prescription for oral vancomycin therapy. Canadian Medical Association Journal 2006; 175(7): 745−8.

7. Janarthanan S, Ditah I, Adler DG, Ehrinpreis MN. Clostridium difficile-associated diarrhoea and proton pump inhibitor therapy: a meta-analysis. Am J Gastroenterol 2012; 107: 1001-10.

8. Brown KA, Khanafer N, Daneman N, et al. Meta-analysis of antibiotics and the risk of community-associated Clostridium difficile infection. Antimicrob Agents Chemother. 2013 May; 57(5):2326-32. doi: 10.1128/AAC.02176-12.

9. Suissa D, Delaney J, Dial S etal. Non-steroidal anti-inflammatory drugs and the risk of Clostridium difficile-associated disease. British Journal of Clinical Pharmacology. 74:2 / 370–375

10. Public Health England. Updated guidance on the management and treatment of Clostridium difficile infection, May 2013

11. National Institute for Health and Care Excellence ESNM1 Clostridium difficile infection: fidaxomicin July 2012,

12. National Institute for Health and Care Excellence. Clostridium difficile infection: risk with broad-spectrum antibiotics March 2015 NICE

13. Deshpande A, Pasupuleti P, Thota P et al. Community-associated Clostridium difficile infection and antibiotics: a meta-analysis. Journal of Antimicrobial Chemotherapy 2013: 68: 1951−61

14. Hu MY, Katchar K, Kyne L, et al. Prospective derivation and validation of a clinical prediction rule for recurrent Clostridium difficile infection. Gastroenterology 2009; 136: 1206-14.

15. Arora V, Kachroo S, Ghantoji SS et al. High Horn’s index score predicts poor outcomes in patients with Clostridium difficile infection Journal of Hospital Infection 79 (2011) 23e26

16. National Institute for Health and Care Excellence IPG485 Faecal microbiota transplant for recurrent Clostridium difficile infection. March 2014