Microbiota restoration for recurrent Clostridioides difficile: Getting one step closer every day!

Clostridioides difficile infection (CDI) is an urgent health threat being the most common healthcare-associated infection, and its management is a clinical conundrum. Over 450 000 infections are seen in the United States with similar incidence seen in the rest of the developed world. The majority of infections seen are mild-moderate with fulminant disease and mortality being rare complications seen in the elderly and in those with comorbidities. The most common complication of CDI is recurrent infection with rates as high as 60% after three or more infections. A dilemma in the management of primary and recurrent CDI is testing due to the high sensitivity of the nucleic acid amplification tests such as the polymerase chain reaction, which leads to clinical false positives if patients are not chosen carefully (with symptoms) before testing. A newer testing regimen involving a 2-step strategy is emerging using glutamate dehydrogenase as a screening strategy followed by enzyme immunoassay for the C. difficile toxin. Microbiota restoration therapies are the cornerstone of management of recurrent CDI to prevent future recurrences. The most common modality of microbiota restoration is faecal microbiota transplantation, which has been tainted with heterogeneity and adverse events such as serious infectious transmission. The success rates for recurrence prevention from microbiota restoration therapies are over 90% compared with less than 50% of recurrence prevention with courses of antibiotics. This has led to development and emergence of standardized microbiota restoration therapies in capsule and enema forms. Capsule-based therapies include CP101 (positive phase II results), RBX7455 (positive phase I results), SER-109 (positive phase III results) and VE303 (ongoing phase II trial). Enema-based therapy includes RBX2660 (positive phase III data). This review summarizes the principles of management and diagnosis of CDI and focuses on emerging and existing data on faecal microbiota transplantation and standardized microbiota restoration therapies.