November is Clostridiodes (or formerly known Clostridium) difficile awareness month. We would like to share interesting details on the infection caused by C. difficile and promising new therapeutic approaches to restore the microbiome instead of secondary antibiotic therapies.
C. difficile infection (CDI) caused by a Gram-positive spore-forming bacterium resulting severe diarrhea and life-threatening colitis (inflammation of the colon). It is estimated over 200,000 infection occurs each year in the Unites States alone, and over 12,000 die annually with a $1B attributed healthcare cost related to medical expenses and extended hospitalizations.
Most cases of CDI occur secondary to antimicrobial therapy frequently seen in elderly and hospitalized patients. Taking antibiotics may destroy the healthy gut microbiome (the 100 trillions of bacteria living in the gut), which could lead to the overgrowth of C. difficile resulting in severe symptoms and health consequences.
The diagnostic tests are based on either detecting the free toxin (produced by C. difficile) or the toxigenic strains of the organism. Toxin enzyme immunoassays (EIAs) and nucleic acid amplification tests (NAATs) are the most commonly used tests for C. difficile detection. There are several challenges in the field of CDI diagnostics around sensitivity, specificity and the distinction between colonization (asymptomatic carrier) and acute infection.
CDI has a recurrence rate of 20-30% resulting in an ongoing challenge to treat these patients. Metronidazole and vancomycin have been the gold standard in the treatment of CDI-associated diarrhea. Other treatments such as fidaxomicin, a narrow-spectrum antibiotic, and monoclonal antibodies like bezlotoxumab, have demonstrated limited improvement in CDI severity and recurrence.
New frontline therapies targeting the intestinal microbiome have been brought to the forefront in order to avoid secondary antimicrobial drugs for CDI patients. Fecal microbiota transplantation (FMT) is a procedure using healthy donor fecal material to restore the healthy gut microbiome and protects against recurrent CDI. FMT has a cure rate of 80-90% with only one administration. FMT can be performed by trained physician in clinical trials for recurrent CDI, but it is still considered an investigational procedure and is not approved by the FDA. In a recent study co-authored by our Chief Medical Officer, Dorottya Nagy-Szakal, MD PhD, the success of pediatric FMT therapy was significantly influenced by underlying co-morbidities in children with recurrent CDI. Several pharmaceutical companies (Ferring/Rebiotix, Seres, Finch Therapeutics, Vedanta Bioscience) are developing microbiota-based live therapeutics against recurrent CDI. Moving away from FMT and donor screening, the development of live bacteria products (under current good manufacturing practices) with demonstrated efficacy and tolerability provides some hope of a potential FDA-approved product to fight against recurrent CDI.
Currently no vaccine has been developed against C. difficile. Some of the latest toxoid vaccine studies showed promises to be deployed in phase 1 and 2 clinical studies. The formulation demonstrated immunogenicity, however the studies had to be stopped early because of reported adverse events. A new aluminum hydroxide formulation with sufficient immunogenicity and acceptable safety profile is currently in phase 3 study.
C. difficile is considered one of the most urgent antibiotic-resistant threats to public health. The CDC urged the implementation of several preventative measures including hand-washing, the avoidance of using unnecessary antibiotics, contact precautions and cleaning in hospitals, and better monitoring in long-term care facilities and high risk areas where patients could contain the bacteria. About 2-5% of the population is asymptomatic carrier that is thought to be a major reservoir of CDI. Interventions to prevent, diagnose, monitor and treat CDI is urgently needed to improve since CDI results in extended and profound consequences for patients and hospitals.
Biotia is a high-complexity molecular diagnostic lab with NYS CLIA accreditation. If you are interested in Biotia’s sequencing service or our software tools to translate your metagenomic data into microbial and antimicrobial resistance information, please contact info@biotia.io. Photo source.
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