Burden of <i>Clostridium difficile</i> Infection in the United States

doi:10.1056/nejmc1505190

Cited by 153 publications

(114 citation statements)

References 34 publications

Supporting

Mentioning

106

Contrasting

Order By: Relevance

“…The higher boundary was the total number of CDI cases in the US in 2011 extracted from Lessa et al [24], while the lower boundary was the result from a meta-analysis to estimate the total burden of CDI cases in the US [25] (For detailed results see Additional file 1). The total annual cost of CDI management was calculated multiplying the average cost of management per case of CDI, with the total number of CDI cases per year in the US (Fig.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2016

View full text Add to dashboard Cite

BackgroundClostridium 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.MethodsWe 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.ResultsThe average cost for CDI case management and average CDI-attributable costs per case were $42,316 (90 % CI: $39,886, $44,765) and $21,448 (90 % CI: $21,152, $21,744) in 2015 US dollars. Hospital-onset CDI-attributable cost per case was $34,157 (90 % CI: $33,134, $35,180), which was 1.5 times the cost of community-onset 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.ConclusionsThis 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1786-6) contains supplementary material, which is available to authorized users.

show abstract

Section: Methodsmentioning

confidence: 99%

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

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Primary treatment for acute infections is antibiotics. However, up to 20 percent of patients experience recurrence of CDI that may be resistant to subsequent treatment with antibiotics 6 . For these patients, novel therapies such as probiotics and fecal microbiota transplant are being tested 7, 8 .…”

Section: Introductionmentioning

confidence: 99%

Amelioration of Clostridium difficile Infection in Mice by Dietary Supplementation With Indole-3-carbinol

et al. 2017

View full text Add to dashboard Cite

Objective To determine the therapeutic effects of dietary supplementation on C. difficile infection (CDI). Background With limited treatment options, the rise of Clostridium difficile-associated disease has spurred on the search for novel therapies. Recent data define a role for the aryl hydrocarbon receptor (AHR) and diet-derived AHR ligands in mucosal immunity. We investigated the efficacy of indole-3-carbinol (I3C), a dietary supplement and AHR precursor ligand, in a murine model of CDI. Methods C57BL/6 (B6), AHR−/− and AHR+/− mice were placed on either grain-based or semi-purified diets with or without I3C prior to and during CDI. Mice were followed clinically for a minimum of 6 days, or euthanized between days 0 and 4 of inoculation for analysis of the inflammatory response and microbiota. Results B6 mice fed an AHR ligand-deficient, semi-purified diet have significantly increased disease severity (p < 0.001) and mortality (p<0.001) compared to mice fed diet containing I3C. The addition of I3C to the diet of AHR null mice had less of an impact than in AHR heterozygous littermates, although some protection was seen. Mice on semi-purified I3C-diet had increased cecal Tregs, ILC3s, and γδ T cells as well as an increased neutrophilic response without increased inflammation or bacterial translocation compared to controls. Conclusions I3C is a powerful treatment to reduce impact of CDI in mice. The findings indicate I3C may be acting through both AHR-dependent and -independent mechanisms in this model. Dietary supplementation with I3C is a potential new therapy for prevention and amelioration of C. difficile disease.

show abstract

“…[1, 2] Morbidity and mortality, particularly associated with recurrent disease, remain problematic, with ~25% of patients experiencing a recurrence of symptoms following treatment. [3, 4] A key contributing factor to the high rates of recurrence associated with CDI is the persistence of C .…”

Section: Introductionmentioning

confidence: 99%

Association of Fidaxomicin with C. difficile Spores: Effects of Persistence on Subsequent Spore Recovery, Outgrowth and Toxin Production

et al. 2016

View full text Add to dashboard Cite

BackgroundWe have previously shown that fidaxomicin instillation prevents spore recovery in an in-vitro gut model, whereas vancomycin does not. The reasons for this are unclear. Here, we have investigated persistence of fidaxomicin and vancomycin on C. difficile spores, and examined post-antibiotic exposure spore recovery, outgrowth and toxin production.MethodsPrevalent UK C. difficile ribotypes (n = 10) were incubated with 200mg/L fidaxomicin, vancomycin or a non-antimicrobial containing control for 1 h in faecal filtrate or Phosphate Buffered Saline. Spores were washed three times with faecal filtrate or phosphate buffered saline, and residual spore-associated antimicrobial activity was determined by bioassay. For three ribotypes (027, 078, 015), antimicrobial-exposed, faecal filtrate-washed spores and controls were inoculated into broth. Viable vegetative and spore counts were enumerated on CCEYL agar. Percentage phase bright spores, phase dark spores and vegetative cells were enumerated by phase contrast microscopy at 0, 3, 6, 24 and 48 h post-inoculation. Toxin levels (24 and 48h) were determined by cell cytotoxicity assay.ResultsFidaxomicin, but not vancomycin persisted on spores of all ribotypes following washing in saline (mean = 10.1mg/L; range = 4.0-14mg/L) and faecal filtrate (mean = 17.4mg/L; 8.4–22.1mg/L). Outgrowth and proliferation rates of vancomycin-exposed spores were similar to controls, whereas fidaxomicin-exposed spores showed no vegetative cell growth after 24 and 48 h. At 48h, toxin levels averaged 3.7 and 3.3 relative units (RU) in control and vancomycin-exposed samples, respectively, but were undetectable in fidaxomicin-exposed samples.ConclusionFidaxomicin persists on C. difficile spores, whereas vancomycin does not. This persistence prevents subsequent growth and toxin production in vitro. This may have implications on spore viability, thereby impacting CDI recurrence and transmission rates.

show abstract

Burden of Clostridium difficile Infection in the United States

Cited by 153 publications

References 34 publications

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

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

Amelioration of Clostridium difficile Infection in Mice by Dietary Supplementation With Indole-3-carbinol

Association of Fidaxomicin with C. difficile Spores: Effects of Persistence on Subsequent Spore Recovery, Outgrowth and Toxin Production

Contact Info

Product

Resources

About