Ridinilazole: A novel therapy for Clostridium difficile infection

Clostridium difficile infection (CDI) is the leading cause of infectious healthcare-associated diarrhoea. Recurrent CDI increases disease morbidity and mortality, posing a high burden to patients and a growing economic burden to the healthcare system. Thus, there exists a significant unmet and increasing medical need for new therapies for CDI. This review aims to provide a concise summary of CDI in general and a specific update on ridinilazole (formerly SMT19969), a novel antibacterial currently under development for the treatment of CDI. Owing to its highly targeted spectrum of activity and ability to spare the normal gut microbiota, ridinilazole provides significant advantages over metronidazole and vancomycin, the mainstay antibiotics for CDI. Ridinilazole is bactericidal against . C. difficile and exhibits a prolonged post-antibiotic effect. Furthermore, treatment with ridinilazole results in decreased toxin production. A phase 1 trial demonstrated that oral ridinilazole is well tolerated and specifically targets clostridia whilst sparing other faecal bacteria. Phase 2 and 3 trials will hopefully further our understanding of the clinical utility of ridinilazole for the treatment of CDI

Clostridium difficile infection.

Infection of the colon with the Gram-positive bacterium Clostridium difficile is potentially life threatening, especially in elderly people and in patients who have dysbiosis of the gut microbiota following antimicrobial drug exposure. C. difficile is the leading cause of health-care-associated infective diarrhoea. The life cycle of C. difficile is influenced by antimicrobial agents, the host immune system, and the host microbiota and its associated metabolites. The primary mediators of inflammation in C. difficile infection (CDI) are large clostridial toxins, toxin A (TcdA) and toxin B (TcdB), and, in some bacterial strains, the binary toxin CDT. The toxins trigger a complex cascade of host cellular responses to cause diarrhoea, inflammation and tissue necrosis - the major symptoms of CDI. The factors responsible for the epidemic of some C. difficile strains are poorly understood. Recurrent infections are common and can be debilitating. Toxin detection for diagnosis is important for accurate epidemiological study, and for optimal management and prevention strategies. Infections are commonly treated with specific antimicrobial agents, but faecal microbiota transplants have shown promise for recurrent infections. Future biotherapies for C. difficile infections are likely to involve defined combinations of key gut microbiota

Cost of hospital management of Clostridium difficile infection in United States - a meta-analysis and modelling study

Background: Clostridium difficile infection (CDI) is the leading cause of infectious nosocomial diarrhoea but the economic costs of CDI on healthcare systems in the US remain uncertain. Methods: We conducted a systematic search for published studies investigating the direct medical cost associated with CDI hospital management in the past 10 years (2005-2015) and included 42 studies to the final data analysis to estimate the financial impact of CDI in the US. We also conducted a meta-analysis of all costs using Monte Carlo simulation. Results: The average cost for CDI case management and average CDI-attributable costs per case were $42,316 (90$ 39,886, $44,765) and$ 21,448 (90 % CI: $21,152,$ 21,744) in 2015 US dollars. Hospital-onset CDIattributable cost per case was $34,157 (90$ 33,134, $35,180), which was 1.5 times the cost of communityonset CDI ($ 20,095 [ 90 % CI: $4991,$ 35,204]). The average and incremental length of stay (LOS) for CDI inpatient treatment were 11.1 (90 % CI: 8.7-13.6) and 9.7 (90 % CI: 9.6-9.8) days respectively. Total annual CDI-attributable cost in the US is estimated US$6.3 (Range:$ 1.9-$ 7.0) billion. Total annual CDI hospital management required nearly 2.4 million days of inpatient stay. Conclusions: This review indicates that CDI places a significant financial burden on the US healthcare system. This review adds strong evidence to aid policy-making on adequate resource allocation to CDI prevention and treatment in the US. Future studies should focus on recurrent CDI, CDI in long-term care facilities and persons with comorbidities and indirect cost from a societal perspective. Health-economic studies for CDI preventive intervention are needed.Sanofi PasteurSCI(E)[email protected]

The Economic Burden of Clostridium difficile infection

Clostridium difficile infection (CDI) leads to significant burden on the healthcare system (e.g., lengthy hospital stay, readmissions). The economic impact associated with CDI in Canada is poorly understood, as only three studies have quantified the burden with results primarily based on expert opinion. This thesis is comprised of three studies to further the understanding of CDI costs. The first study was a systematic review of CDI costing literature. This study identified 45 cost of illness studies that found an economic burden associated with CDI. Mean attributable CDI costs ranged from $10,961 to$36,960 per hospitalized patient (2014 Canadian dollars, range derived from six studies with similar patient populations). The costing methods across the 45 studies were heterogeneous and some studies did not follow standard cost of illness methodology (e.g., provide a justified study viewpoint, conduct sensitivity analyses). The second study examined the economic burden of hospital-acquired CDI using linked health administrative data and a population-based propensity-score matched cohort design. This study evaluated costs unadjusted and adjusted for survival, with the latter estimating costs using the phase of care approach. The results were stratified by elective (e.g., planned) and non-elective admissions. Mean attributable 1-year costs unadjusted for survival were $48,029 (95$43,315-$52,871) for elective admission subjects and$40,889 (95%CI, $39,768-$42,010) for non-elective admission subjects. Mean attributable 1-year costs adjusted for survival were $32,151 (95$28,192-$36,005) for elective admission subjects and$21,909 (95%CI, $21,221-$22,609) for non-elective admission subjects. The third study examined the economic burden of community-onset CDI also using a population-based propensity-score matched cohort design and evaluating costs unadjusted and adjusted for survival. Mean attributable 1-year costs were $13,217 (95$12,062-$14,388) unadjusted for survival and$10,700 (95%CI, $9,811-$11,645) adjusted for survival. Both the second and third studies were from the Ontario healthcare payer perspective. Overall, CDI is associated with considerable economic burden. Decision makers can use the absolute and relative results of the three studies to assess CDI-related interventions. This body of work contributes estimates to the economic burden of CDI and demonstrates the use of health administrative data to estimate the costs of infectious diseases.Ph.D.2017-11-30 00:00:0