Fidaxomicin
Regulatory sources consulted
Approved indications
- Treatment of Clostridioides difficile infections, including C. difficile-associated diarrhoea, in adults and paediatric patients weighing at least 12.5 kg.
Contraindications
Absolute
- Hypersensitivity to fidaxomicin or any excipient.
Clinical warnings
- Major warning · Discontinue and manage appropriately if a severe allergic reaction occurs; use with caution with known macrolide allergy. — AEMPS CIMA, Dificlir, ficha técnica 11733004, sección 4.4
- Major warning · Use with caution in severe renal impairment, moderate or severe hepatic impairment, pseudomembranous colitis and fulminant or life-threatening infection. — AEMPS CIMA, Dificlir, ficha técnica 11733004, sección 4.4
Drug interactions
- ModerateCiclosporin and other potent P-glycoprotein inhibitors
Mechanism: Fidaxomicin is a P-glycoprotein substrate; ciclosporin increased exposure to fidaxomicin and its active metabolite in the cited study.
Recommendation: Concomitant administration with potent P-glycoprotein inhibitors is not recommended; if unavoidable, use caution.
https://cima.aemps.es/cima/dochtml/ft/11733004/FT_11733004.html
Adverse events
Common (≥1%)
Nausea · Vomiting · Constipation · Abdominal distension · Flatulence
Rare but serious
Angioedema · Hypersensitivity-related dyspnoea
Pregnancy and lactation
As a precaution, use during pregnancy should preferably be avoided. During breastfeeding, decide whether to stop breastfeeding or treatment after weighing benefits for the child and mother.
Recent literature (PubMed)
Clostridioides difficile infection is the most common healthcare-associated infection in the United States, with potential life-threatening complications and a significant impact on the costs of care. Antibiotic stewardship as well as discontinuation of chronic acid suppressive therapy are key for its prevention and treatment. Effective infection management requires appropriate interpretation of diagnostic tests, as well as the use of vancomycin and fidaxomicin as first-line treatment. Novel treatments such as Bezlotoxumab, fecal microbiota transplant, and live biotherapeutic products are proven effective in recurrent C. difficile infection and address dysbiosis.
This clinical practice guideline is a focused update on management of Clostridioides difficile infection (CDI) in adults specifically addressing the use of fidaxomicin and bezlotoxumab for the treatment of CDI. This guideline was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA). This guideline is intended for use by healthcare professionals who care for adults with CDI, including specialists in infectious diseases, gastroenterologists, hospitalists, pharmacists, and any clinicians and healthcare providers caring for these patients. The panel's recommendations for the management CDI are based upon evidence derived from topic-specific systematic literature reviews. Summarized below are the recommendations for the management of CDI in adults. The panel followed a systematic process which included a standardized methodology for rating the certainty of the evidence and strength of recommendation using the GRADE approach (Grading of Recommendations Assessment, Development, and Evaluation). A detailed description of background, methods, evidence summary and rationale that support each recommendation, and knowledge gaps can be found online in the full text. No information is available on the use of fidaxomicin during breastfeeding. Because it is poorly absorbed orally, it is not likely to reach the bloodstream of the infant or cause any adverse effects in breastfed infants.
Clostridioides (formerly Clostridium) difficile is the most important infectious cause of antibiotic-associated diarrhea worldwide and a leading cause of healthcare-associated infection in the United States. The incidence of C. difficile infection (CDI) in children has increased, with 20 000 cases now reported annually, also posing indirect educational and economic consequences. In contrast to infection in adults, CDI in children is more commonly community-associated, accounting for three-quarters of all cases. A wide spectrum of disease severity ranging from asymptomatic carriage to severe diarrhea can occur, varying by age. Fulminant disease, although rare in children, is associated with high morbidity and even fatality. Diagnosis of CDI can be challenging as currently available tests detect either the presence of organism or disease-causing toxin but cannot distinguish colonization from infection. Since colonization can be high in specific pediatric groups, such as infants and young children, biomarkers to aid in accurate diagnosis are urgently needed. Similar to disease in adults, recurrence of CDI in children is common, affecting 20% to 30% of incident cases. Metronidazole has long been considered the mainstay therapy for CDI in children. However, new evidence supports the safety and efficacy of oral vancomycin and fidaxomicin as additional treatment options, whereas fecal microbiota transplantation is gaining popularity for recurrent infection. Recent advancements in our understanding of emerging epidemiologic trends and management of CDI unique to children are highlighted in this review. Despite encouraging therapeutic advancements, there remains a pressing need to optimize CDI therapy in children, particularly as it pertains to severe and recurrent disease.
The chronic inflammatory bowel diseases (IBD), Crohn's disease, and ulcerative colitis, are associated with an increased risk of symptomatic Clostridium difficile infection (CDI). CDI may also masquerade as an IBD flare and complicate IBD management. This review provides a comprehensive overview of the epidemiology, diagnosis, and treatment of CDI in IBD patients. CDI remains common in IBD with complications including flares in disease activity, recurrent CDI episodes, and prolonged hospital stays. Newer IBD therapeutics including vedolizumab, ustekinumab, and tofacitinib are less likely to cause severe CDI. A high index of suspicion, rapid testing via a two-step method, and prompt treatment with vancomycin or fidaxomicin are paramount to managing CDI in IBD patients. Strategies to prevent recurrent CDI (rCDI) include the monoclonal antibody bezlotoxumab as well as fecal microbiota transplantation (FMT). FMT has a robust profile of safety and effectiveness in preventing rCDI in adults and children. Clinicians must remain vigilant in the prompt diagnosis and treatment of CDI in IBD patients. Corticosteroids, unnecessary antibiotics, and ongoing colonic inflammatory disease are modifiable risk factors. Improved infection control measures, newer IBD medications, and using effective CDI treatments will facilitate a reduced burden of severe CDI and complications for IBD patients.