Microbiology & Infectious Diseases
Treating Clostridioides difficile infections
This interactive case study was organised and funded by Tillotts Pharma.
Local prescribing conditions for fidaxomicin may vary. Please refer to prescribing information in your country of practice. Healthcare professionals are asked to report any suspected adverse reactions. Details on adverse event reporting are given at the end of this case study.
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Disclosure
These interactive case studies were developed with support from Francisco Javier Gonzalez, Internal Medicine Specialist, Hospital Universitario Toledo, Spain.
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Disclaimer
These are hypothetical patient cases and outcomes may not be reflective of clinical studies or real-life circumstances. The mention of these agents and their uses is intended solely for educational purposes and should not be considered an endorsement or recommendation for their use outside of approved indications. Please always consult guidelines and local prescribing information in your country of practice, as information may vary.
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Patient Background and Past Medical History
2/20
Personal history: Male, 70 years old, no known drug allergies.
He is a former smoker with hypertension and fits the clinical criteria for COPD. He does not have diabetes, dyslipidaemia, or known heart disease.
He has spondylarthrosis, gonarthrosis, and benign prostatic hypertrophy.
His usual treatment schedule includes valsartan/amlodipine/hydrochlorothiazide (HCT) 160/5/12.5 1-0-0; dutasteride/tamsulosin 0-0-1.
He is Admitted to the Hospital…
3/20
He is admitted to the hospital for a hip fracture. Receives surgical prophylaxis with cefazolin. Given positive urine culture for Escherichia coli, ceftriaxone is also prescribed for 7 days. For analgesia, paracetamol and ketorolac are alternated and pantoprazole 40 mg is administered intravenously.
Treatment upon discharge: enoxaparin 4,000 IU/24 hours (discontinue depending on mobility); omeprazole 40 mg 1-0-0; valsartan/amlodipine/HTC 160/5/12.5 1-0-0; dutasteride/tamsulosin 0-0-1; and paracetamol 1 g and dexketoprofen 25 mg alternating if in pain.
Fifteen Days After He is Discharged, He Presents with Watery Stools
4/20
After 15 days, he presents with watery stools without pathological products and abdominal pain, but is in good general health. His doctor refers him to the hospital emergency department, where routine blood tests are requested (leukocytes: 10,500 /μL; creatinine: 0.78 mg/dL). A microbiological study is requested: positive glutamate dehydrogenase (GDH) test, positive toxin A/B by enzyme-immunoassay, and positive Nucleic Acid Amplification Test (NAAT) for C. difficile.
A first episode of C. difficile infection (CDI) is diagnosed, and oral vancomycin 125 mg every 6 hours for 10 days is started, with clinical resolution and disappearance of diarrhoea on the third day. Treatment at discharge: Omeprazole 40 mg 1-0-0; valsartan/amlodipine/HTC 160/5/12.5 1-0-0; dutasteride/tamsulosin 0-0-1; paracetamol 1 g if pain; and oral vancomycin 125 mg every 6 hours for 10 days.
25 days after
Fifteen Days After Vancomycin Treatment (10 days)…
5/20
He presents with a new episode of diarrhoea: Click to explore >>
He has not taken any laxatives or enemas, and does not attribute it to anything he has eaten. No other family members are affected.
Current treatment: Omeprazole 20 mg 1-0-0; valsartan/amlodipine/HCT 160/5/12.5 1-0-0; and dutasteride/tamsulosin 0-0-1.
The patient returns to Accident and Emergency with diarrhoea (>3 bowel movements/day), without fever but with severe abdominal pain.
A 70-year-old male who successfully completed a 10-day course of oral vancomycin for a first episode of CDI 15 days ago now presents with a new onset of severe watery diarrhoea and intense abdominal pain. Based on this timeline and clinical context, what is the most likely clinical diagnosis?
6/20
Treatment failure of the initial CDI
Recurrence of CDI
New episode of community-acquired infectious diarrhoea unrelated to CDI with asymptomatic C. difficile colonisation
A
B
C
Van Prehn J et al. Recurrent Clostridioides difficile infections. JAMA. 2025;334(23):2128-9.
Examinations and Additional Tests
7/20
Physical examination: Good general condition, haemodynamically stable, eupnoeic at rest, afebrile. Mild dryness of mucous membranes. Abdomen: Increased bowel sounds, painful on diffuse palpation with no clear signs of abdominal irritation.
Additional tests requested: Basic blood tests Stool culture: determination of C. difficile Abdominal X-ray (of little use)
An Abdominal X-ray and Complete Blood Count Were Carried Out
8/20
Abdominal X-ray: poorly framed, psoas lines preserved, non-specific luminogram (normal)
Which combination of microbiological tests confirmed the diagnosis of CDI? Select all which apply:
9/20
Johnson S et al. Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults. Clin Infect Dis. 2021;73(5):e1029-44.
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Treatment Failure and Recurrence
10/20
Treatment failure is defined as the persistence of clinical symptoms of CDI (diarrhoea, abdominal pain, fever, leukocytosis) and/or the absence of clinical resolution after completing an adequate course of targeted antibiotics (e.g., vancomycin or fidaxomicin), usually assessed 5–7 days after starting treatment.
1. Johnson S et al. Clinical practice guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 focused update guidelines on management of Clostridioides difficile infection in adults. Clin Infect Dis. 2021;73(5):e1029-44. 2. Kelly CR et al. ACG clinical guidelines: prevention, diagnosis, and treatment of Clostridioides difficile infections. Am J Gastroenterol. 2021;116(6):1124-47. 3. Poylin V et al. The American Society of Colon and Rectal Surgeons clinical practice guidelines for the management of Clostridioides difficile infection. Dis Colon Rectum. 2021;64(6):650-68.
Recurrence is defined as the reappearance of CDI symptoms (diarrhoea and positive microbiological findings) after complete resolution of the initial episode, within the first 2–8 weeks after completing treatment. Recurrence may be due to the persistence of spores (relapse) or a new infection by a different strain (reinfection). Most recurrences occur within the first 30 days and are associated with factors such as advanced age, antibiotic use, PPI use, and previous hospitalisation.
The Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) consider failure to be the absence of clinical improvement or the need to change antibiotics due to lack of response.
Based on the clinical presentation, a 70-year-old male presenting with a documented first recurrence of CDI 15 days after successful completion of a 10-day course of oral vancomycin, how would you approach treatment?
11/20
Fidaxomicin 200 mg every 12 hours for 10 days
Oral vancomycin 125 taper and pulse regimen
Faecal microbiota transplantation
Van Prehn J et al. European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults. Clin Microbiol Infect. 2021;27(Suppl 2):S1-21.
Intravenous vancomycin combined with oral metronidazole
Diagnosis: Recurrence of C. difficile Infection
12/20
The diagnostic criteria to be met are:
Recurrence of clinical symptoms consistent with CDI (watery diarrhoea, abdominal pain, fever, leukocytosis) after complete resolution of a previously treated and documented episode, within the first 2–8 weeks after completion of targeted antibiotic treatment. Microbiological confirmation by detection of C. difficile toxins in unformed stool samples, using combined tests: GDH test or NAAT as screening, followed by enzyme immunoassay for toxins, as recommended by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). It should be remembered that it is essential to avoid retesting in the absence of symptoms and to rule out asymptomatic colonisation. Exclusion of other causes of diarrhoea (infectious, drug-related, metabolic) and temporal correlation with a history of CDI and present risk factors (age ≥65 years, recent use of antibiotics, proton pump inhibitors [PPI], hospitalisation).
Treatment
13/20
In all cases, review proton pump inhibitor (PPI) use. In this patient’s case of first recurrence previously treated with vancomycin, this aligns with CDI ESCMID 2021 Guidelines, which recommend fidaxomicin 200 mg every 12 hours for 10 days.
Obtained from Van Prehn J et al. Clin Microbiol Infect. 2021;27 Suppl 2:S1–21. BID: twice a day; CDI: Clostridioides difficile infection; FMT: faecal microbiota transplantation; QID: four times a day; SoC: standard of care; TID: three times a day.
*Risk stratification for risk of recurrence may be applied for selective use of fidaxomicin in case of limited access or resources. **Consider extended fidaxomicin: 200 mg BID on Day 1–5, 200 mg q48h on Day 7–25. Most important risk factor for recurrence is age >65–70 years. Additional risk factor(s) to consider are healthcare-associated CDI, prior hospitalisations ≤3 months, prior CDI episode, continued non-CDI antibiotic use, and PPI therapy. The risk of recurrence is assumed higher with more risk factors present. $Vancomycin taper and pulse: 2 weeks 125 mg QID, followed by 1 week 125 mg BID, then 1 week 125 mg QID, then 1 week 125 mg q48h, and finally 125 mg q72h for 1 week. $$Rectal or nasoduodenal delivery.
CDI ESCMID guidelines 2021
Fidaxomicin was compared with vancomycin in several studies for the treatment of CDI. Which statement about fidaxomicin versus vancomycin is not correct?
14/20
Bactericidal against C. difficile
Inhibition of spores and toxins production
Significant reduction of the recurrence rates of CDI
Broader spectrum activity against CDI, which can lead to a disruption of the microbiota
References
1. Babakhani F et al. Fidaxomicin inhibits spore production in Clostridium difficile. Clin Infect Dis. 2012;55(Suppl2):S162-9. 2. Louie TJ et al. Fidaxomicin preserves the intestinal microbiome during and after treatment of Clostridium difficile infection (CDI) and reduces both toxin reexpression and recurrence of CDI. Clinical Infectious Diseases. 2012;55(suppl 2). 3. Louie TJ et al. Fidaxomicin versus vancomycin for Clostridium difficile infection. New England Journal of Medicine. 2011;364(5): 422-31. 4. Cao X et al. Basis of narrow-spectrum activity of fidaxomicin on Clostridioides difficile. Nature. 2022;604(7906):541-5.
Fidaxomicin Versus Vancomycin
15/20
In a Phase III clinical trial, adults (n=548) with acute C. difficile infection were randomly assigned to receive fidaxomicin (200 mg/2/d) or vancomycin (125 mg/4/d), to compare efficacy and safety. Primary endpoint: clinical cure (resolution of symptoms and no need for further therapy for C. difficile infection as of the second day after the end of the course of therapy). Secondary endpoint: recurrence of C. difficile infection and global cure.
Louie TJ et al.; OPT-80-003 Clinical Study Group. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med. 2011;364(5):422-31.
Fidaxomicin treatment was associated with a significantly lower rate of recurrence than vancomycin in both the modified intention-to-treat population (P=0.005) and the per-protocol population (P=0.004).
Fidaxomicin demonstrates a 45% relative reduction in recurrences and a correspondingly improved rate of global cure versus vancomycin.
-45%
Preserving the Microbiota May Result in a Lower Risk of Recurrence
16/20
Louie et al. observed that vancomycin causes more disruption to the microbiota than fidaxomicin, and this collateral damage contributes to CDI recurrence.
1. Louie TJ et al. Fidaxomicin preserves the intestinal microbiome during and after treatment of Clostridium difficile infection (CDI) and reduces both toxin reexpression and recurrence of CDI. Clin Infect Dis. 2012;55(Suppl 2):S132-42. 2. Gonzales-Luna AJ et al. Gut microbiota changes associated with Clostridioides difficile infection and its various treatment strategies. Gut Microbes. 2023;15(1):2223345.
The microbiota-preserving properties of fidaxomicin provide a selective therapy against C. difficile, resulting in a more robust microbiome and a lower risk of recurrent disease.
Species such as Bacteroides (Prevotella, Firmicutes C. leptum) and Bifidobacteria play a beneficial role in maintaining a healthy microbiome.
CDI is a prominent clinical example of the consequences of disrupting the normal gut microbiota. How can a healthy microbiota help prevent CDI?
17/20
By competing with C. difficile and maintaining an unfavourable environment in the gut for C. difficile infection
By promoting the growth of C. difficile to strengthen immunity
By directly neutralising C. difficile toxins
1. Louie TJ et al. Fidaxomicin preserves the intestinal microbiome during and after treatment of Clostridium difficile infection (CDI) and reduces both toxin reexpression and recurrence of CDI. Clin Infect Dis. 2012;55 Suppl 2(Suppl 2):S132-42. 2. Crobach MJT. Understanding Clostridium difficile colonization. Clin Microbiol Rev. 2018;31(2):e00021-17.
It has no influence on the prevention of CDI
Which of the following factors, identified in the patient's history during his initial hospitalisation, is an independent risk factor for the recurrence of CDI?
18/20
Clinical criteria for COPD
Benign prostatic hypertrophy
Advanced age (>65 years)
Chronic use of enoxaparin
1. Di Bella S et al. Clostridioides difficile infection: history, epidemiology, risk factors, prevention, clinical manifestations, treatment, and future options. Clin Microbiol Rev. 2024;37(2):e0013523. 2. Van Rossen TM et al. Prognostic factors for severe and recurrent Clostridioides difficile infection: a systematic review. Clin Microbiol Infect. 2022;28(3):321-31. 3. Van Prehn J et al. European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults. Clin Microbiol Infect. 2021;27(Suppl 2):S1-21.
Conclusion
19/20
After 4 days of treatment with fidaxomicin, the patient reaches clinical resolution and disappearance of diarrhoea with no further recurrence. Looking back, the patients at high risk of recurrence or treatment failure are:
Our patient was 70 years old, had recently been hospitalised, and had received antibiotic therapy with cephalosporins, which are risk factors for recurrence. Therefore, if available, he should have been treated with fidaxomicin in the first episode.
1. Di Bella S et al. Clostridioides difficile infection: history, epidemiology, risk factors, prevention, clinical manifestations, treatment, and future options. Clin Microbiol Rev. 2024;37(2):e0013523. 2. van Rossen TM et al. Prognostic factors for severe and recurrent Clostridioides difficile infection: a systematic review. Clin Microbiol Infect. 2022;28(3):321-31. 3. Van Prehn J et al. European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults. Clin Microbiol Infect. 2021;27(Suppl 2):S1-21.
≥65 years old
Immunocompromised
Hypervirulent strain
Recent hospitalisation
Concomitant use of antibiotics
THANK YOU
20/20
Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Tillotts Pharma at www.tillotts.com/products/dificlir/.
