Successful treatment of recurrent<i>Clostridioides difficile</i>infection by administration of crushed fidaxomicin via gastro-jejunal tube

Clostridioides difficile infection (CDI) is a common hospital-acquired infection and an increasingly frequent cause of morbidity and mortality among hospitalized patients. In the USA, C. difficile is now the single most common cause of healthcare-associated infection and is estimated to cause as much as $4.8 billion in excess healthcare costs for acute care facilities.1 Current IDSA guidelines suggest oral fidaxomicin for the treatment of both initial and recurrent CDI episodes over the previously recommended vancomycin.2 However, many hospitalized patients are unable to take medications orally and rely on enteral tubes for medication administration. While the vancomycin product monograph supports administration of vancomycin via nasogastric tube, administration of fidaxomicin via enteral tube is not recommended by the manufacturer and has not been validated.3,4 There is thus no validated way of treating patients who cannot tolerate oral intake with guideline-recommended first-line therapy. We report a case in which fidaxomicin was administered through a gastric-jejunal (GJ) tube with successful outcome. Written informed consent was obtained from the patient’s substitute decision-maker for the publication of this report. The adult patient originally developed anoxic brain injury secondary to severe COVID-19 pneumonia requiring permanent tracheostomy and GJ tube placement. He developed multiple respiratory and urinary tract infections in the subsequent months with resistant organisms including Citrobacter spp. and Pseudomonas aeruginosa. These required numerous courses of broad-spectrum antibiotics which unfortunately resulted in recurrent CDI. The first CDI was treated with a 14 day course of oral vancomycin, and the first recurrence was treated with a vancomycin tapering regimen. He presented to the hospital with several days of tachycardia, diaphoresis, diarrhoea and abdominal pain. On admission he was tachycardic with a pulse of 117 beats per minute and a WBC count of 15.7 × 109 cells/L. He was having approximately six watery stools per day. CT scan of the abdomen showed signs of colitis and C. difficile toxin assay was positive. The patient was diagnosed with a second recurrence of CDI and was treated with a 14 day course of enteral vancomycin and a concurrent 10 day course of enteral metronidazole, with plans for a slow vancomycin taper. He initially responded well to therapy with resolution of fever and tachycardia and bowel movements decreasing to two semi-formed stools per day at the end of the 14 day treatment course. However, on the third day of the vancomycin taper he developed abrupt onset tachycardia of 116 beats per minute and leucocytosis with WBC count increasing from 10.8 to 18.8 × 109 cells/L, and recurrent diarrhoea with five watery bowel movements per day. A repeat C. difficile toxin assay was positive. Imaging at this point was consistent with large bowel ileus and mild inflammatory changes, with no signs of megacolon. A urinary culture drawn from an indwelling catheter also grew P. aeruginosa, and the treating clinician elected to treat a possible catheter-associated urinary tract infection. Given his previous failures of vancomycin treatment, he was then initiated on fidaxomicin 200 mg via enteral tube twice daily × 10 days for CDI in addition to piperacillin/tazobactam 4.5 g IV q6h × 7 days for catheter-associated urinary tract infection. The fidaxomicin tablet was crushed and mixed with 20 mL of water, then administered through a 16-French GJ tube. The patient continued to have between two and four loose bowel movements a day and two C. difficile toxin assays performed on treatment Day 5 and post-treatment Day 1 were negative. Alternative causes for the persistent loose stools included multiple courses of systemic antibiotics, proton-pump inhibitor and zinc therapy, and enteral feed-related diarrhoea. The patient was discharged 10 days after completing fidaxomicin therapy with stable bowel movements and no signs of sepsis. While fidaxomicin is well established as an oral treatment option for CDI, there is limited experience with alternative routes of administration. In vitro studies have demonstrated a 96% recovery of fidaxomicin when crushed, mixed in water and passed through a nasogastric tube.5 Subsequent case reports have demonstrated successful treatment of CDI through nasogastric tubes.6,7 To our knowledge, this is the first case of CDI treatment with fidaxomicin administered via a GJ tube. Taken together with the existing evidence, this case report supports enteral tube administration of fidaxomicin as an option for CDI treatment in patients who are unable to take oral medications. We encourage further research studies to validate enteral tube administration of fidaxomicin given its importance for treatment of CDI in patients unable to take oral medications. This study was carried out as part of our routine work. None to declare.

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