Diagnosis and management of Clostridioides difficile

Definition and risk factors. Clostridioides difficile is a Gram-positive, spore-forming, toxin-producing anaerobe causing antibiotic-associated diarrhoea and pseudomembranous colitis through disruption of the colonic microbiota and elaboration of toxins A and B. Risk factors: antibiotics — especially clindamycin, fluoroquinolones, third-generation cephalosporins, carbapenems and broad-spectrum penicillins — age 65 and over, hospitalisation and long-term care residence, proton pump inhibitors, previous infection, enteral tube feeding, abdominal surgery, chemotherapy and comorbidity. Older adults are the highest-risk group and have the highest mortality and the highest recurrence rate.

Clinical spectrum. Asymptomatic colonisation is common in long-term care residents — do not test and do not treat. Mild-to-moderate infection: watery diarrhoea (three or more unformed stools in 24 hours), cramping abdominal pain, low-grade fever and leucocytosis. Severe infection: white cell count ≥15,000/mm³ or serum creatinine >1.5 mg/dL. Fulminant infection: hypotension or shock, ileus, or toxic megacolon — which may present with a paradoxical reduction in diarrhoea as the colon becomes atonic, a dangerous trap. Kane's advises considering C. difficile in any long-term care resident with fever, abdominal cramps and diarrhoea with or without blood or white cells in the stool.

Diagnosis. Test only unformed, diarrhoeal stool from a symptomatic patient. Do not test formed stool, do not repeat within 7 days, and never perform a test of cure — the assays stay positive for weeks. Use a two-step algorithm: a sensitive screening test — glutamate dehydrogenase (GDH) antigen or a NAAT/PCR for the toxin gene — followed by a specific confirmatory toxin A/B enzyme immunoassay. GDH-positive with toxin-positive confirms infection; both negative excludes it; a discordant NAAT-positive but toxin-negative result may represent colonisation and needs clinical judgement. Adjuncts: CBC, creatinine, albumin, lactate; abdominal radiograph or CT if fulminant disease is suspected; and flexible sigmoidoscopy showing pseudomembranes when the diagnosis remains uncertain.

General measures. Stop the precipitating antibiotic wherever possible, or narrow it; stop the proton pump inhibitor if it has no indication; avoid antimotility agents (loperamide, opiates) in severe disease; correct fluid and electrolyte losses. Infection control: single room with contact precautions, gloves and gowns; hand washing with soap and water — alcohol hand rub does not kill spores; and environmental cleaning with a sporicidal, chlorine-based agent. These are the highest-yield infection-control points for a geriatrics paper.

Treatment of the initial episode. Oral fidaxomicin 200 mg twice daily for 10 days is now preferred, because it produces markedly lower recurrence; oral vancomycin 125 mg four times daily for 10 days is an acceptable alternative and remains the pragmatic first choice in India where cost is limiting. Metronidazole is no longer first-line and is reserved for mild disease where neither agent is available, or as adjunctive intravenous therapy in fulminant disease. Fulminant infection: oral or nasogastric vancomycin 500 mg four times daily plus intravenous metronidazole 500 mg eight-hourly, with vancomycin retention enemas if there is ileus, and early surgical consultation for subtotal colectomy or diverting loop ileostomy with colonic lavage.

Recurrence — the dominant problem in older adults. Recurrence occurs in 20–25% after a first episode and 40–60% after subsequent episodes. First recurrence: fidaxomicin (including the extended-pulsed regimen) if vancomycin was used first, or a tapering and pulsed vancomycin course. Second and later recurrences: tapered/pulsed vancomycin, vancomycin followed by rifaximin, bezlotoxumab — a single-infusion monoclonal antibody against toxin B, used as an adjunct but with caution in heart failure — or faecal microbiota transplantation, which achieves cure rates above 85%.

The therapeutic landscape has changed with the approval of two standardised live biotherapeutic microbiome products for the prevention of recurrent infection — faecal microbiota, live-jslm (Rebyota), given rectally, and faecal microbiota spores, live-brpk (Vowst), given as oral capsules — which provide regulated, quality-controlled, donor-screened alternatives to conventional faecal microbiota transplantation. These followed the 2021 IDSA/SHEA focused update, which established fidaxomicin in preference to vancomycin for both initial and recurrent episodes and introduced bezlotoxumab as an adjunct for patients with an episode in the preceding six months. A 2024 Emerging Infections Network survey found uptake of fidaxomicin still limited by cost, so oral vancomycin remains the realistic first-line agent in most Indian hospitals, with fidaxomicin reserved for those at highest risk of recurrence.