Recurrent<i>Clostridium difficile</i>Infection: Risk Factors, Treatment, and Prevention

Song, Ju Yeon; Kim, You Sun

doi:10.5009/gnl18071

Cited by 135 publications

(119 citation statements)

References 98 publications

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“…Known risk factors for an initial CDI episode include recent systemic antimicrobial therapy, older age (!65 years), healthcare exposure, and underlying chronic comorbidities, among others 6 . Risk factors for rCDI are largely the same, but also include previous CDI severity, and presence of hypervirulent strain, NAP1/BI/027 7,8 .…”

Section: Introductionmentioning

confidence: 99%

Healthcare resource utilization and direct medical costs associated with index and recurrent Clostridioides difficile infection: a real-world data analysis

Feuerstadt

Stong

Dahdal

et al. 2020

Journal of Medical Economics

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Aims: This study aimed to evaluate all-cause economic outcomes, healthcare resource utilization (HRU), and costs in patients with Clostridioides difficile infection (CDI) and recurrent CDI (rCDI) using commercial claims from a large database representing various healthcare settings. Materials and methods: A retrospective analysis of commercial claims data from the IQVIA PharMetrics Plus database was conducted for patients aged 18-64 years with CDI episodes requiring inpatient stay with CDI diagnosis code or an outpatient medical claim for CDI plus a CDI treatment. Index CDI episodes occurred between 1 January 2010 and 30 June 2017, including only those where patients were observable 6 months before and 12 months after the index episode. Each CDI episode was followed by a 14-d claim-free period. rCDI was defined as another CDI episode within an 8-week window following the claim-free period. HRU, all-cause direct medical costs and time to rCDI were calculated over 12 months and stratified by number of rCDI episodes. Results: A total of 46,571 patients with index CDI were included. Mean time from one CDI episode to the next was approximately 1 month. In the 12-month follow-up period, those with no recurrence had 1.4 inpatient visits per person and those with 3 or more recurrences had 5.8. Most patients with 3 or more recurrences had 2 or more hospital admissions. The mean annual, total all-cause direct medical costs per patient were $71,980 for those with no recurrence and $207,733 for those with 3 or more recurrences. Limitations: The study included individuals 18-64 years only. A stringent definition of rCDI was used, which may have underestimated the incidence of rCDI. Conclusions: CDI and rCDI are associated with substantial healthcare resource utilization and direct medical costs. Timing of recurrences can be predictable, providing a window of opportunity for interventions. Prevention of multiple rCDI appears essential to reduce healthcare costs.

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Section: Introductionmentioning

confidence: 99%

Healthcare resource utilization and direct medical costs associated with index and recurrent Clostridioides difficile infection: a real-world data analysis

Feuerstadt

Stong

Dahdal

et al. 2020

Journal of Medical Economics

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“…Although oral administration of antibiotics is the standard rst-line therapy for CDI, antibiotics perturb the commensal gut microbiota and decrease colonization resistance against other pathogens [9,10]. Approximately 15% to 30% of CDI patients therefore experience recurrent CDI (rCDI) resulting from either a relapse of the previous CDI or reinfection [11]. Moreover, antibiotic therapies during CDI treatment may promote the expansion of antibiotic resistant organisms (AROs) such as vancomycin resistant Enterococci (VRE) [12,13].…”

Section: Introductionmentioning

confidence: 99%

Impact of investigational microbiota therapeutic RBX2660 on the gut microbiome and resistome revealed by a placebo-controlled clinical trial

Kwak

Choi

Hink

et al. 2020

Preprint

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Background. Intestinal microbiota restoration can be achieved by complementing a subject’s perturbed microbiota with that of a healthy donor. Recurrent Clostridioides difficile infection (rCDI) is one key application of such treatment. Another emerging application of interest is reducing antibiotic resistant genes (ARGs) and organisms (AROs). In this study, we investigated fecal specimens from a multicenter, randomized, double-blind, placebo-controlled phase 2b study of microbiota-based investigational drug RBX2660. Patients were administered either placebo, 1 dose of RBX2660 and 1 placebo, or 2 doses of RBX2660 via enema and longitudinally tracked for changes in their microbiome and antibiotic resistome.Results. All patients exhibited significant recovery of gut microbiome diversity and a decrease of ARG relative abundance during the first 7 days post-treatment. However, the microbiome and resistome shifts towards average configurations from unperturbed individuals were more significant and longer-lasting in RBX2660 recipients compared to placebo. We quantified microbiome and resistome modification by RBX2660 using a novel ‘transplantation index’ metric. We identified taxonomic and metabolic features distinguishing the baseline microbiome of non-transplanted patients and taxa specifically enriched during the process of transplantation. We elucidated the correlation between resistome and taxonomic transplantations and post-treatment dynamics of patient-specific and RBX2660-specific ARGs. Whole genome sequencing of AROs cultured from RBX2660 product and patient samples indicate ARO eradication in patients via RBX2660 administration, but also, to a lesser extent, introduction of RBX2660-derived AROs.Conclusions. Through shotgun metagenomic sequencing, we elucidated the effects of RBX2660 in the microbiome and resistome. Antibiotic discontinuation alone resulted in significant recovery of gut microbial diversity and reduced ARG relative abundance, but RBX2660 administration more rapidly and completely changed the composition of patients’ microbiome, resistome, and ARO colonization by transplanting RBX2660 microbiota into the recipients. Although ARGs and AROs were transmitted through RBX2660, the resistome post-RBX2660 more closely resembled that of the administered product—a proxy for the donor—than an antibiotic perturbed state.Trial registration: NCT02299570. Registered 19 November 2014, https://clinicaltrials.gov/ct2/show/NCT02299570

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“…The recurrence rate obtained (53.84%) was higher than that found in the medical literature. About 15-47.2% of patients initially treated for CDI developed, in the following weeks, at least one new episode of CDI [2,19]. The high relapse rate obtained in the study could be explained by the use of metronidazole as the first line of treatment, according to the national CDI treatment guidelines.…”

Section: Associated Factors With Recurrent CDImentioning

confidence: 75%

“…Furthermore, the risk for new diarrhea episodes increases from 25 to 65% after the first recurrence episode [1]. Each new episode raises the risk of a future episode by about 20% [2].…”

Section: Introductionmentioning

confidence: 99%

Risk Factors Associated with Recurrent Clostridioides difficile Infection

et al. 2020

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Clostridioides difficile (CD) is responsible for nosocomial diarrhea syndrome with possible severe progression. Recurrence of the disease induces higher health system costs, as well as exposes patients to additional health risks. Patients with recurrence of this disease are difficult to identify, so the purpose of this study is to quantify various demographic, clinical, and treatment factors that could prevent further progression to recurrence of the disease. In the period 2018–2019, about 195 patients were diagnosed with more than one episode of CDI in the three months following the first episode. The recurrence rate for CDI was 53.84% (60.95% for one episode and 39.05% for multiple episodes). Most commonly afflicted were 60–69-year-old patients, or those with higher Charlson Comorbidity Index (CCI). Multiple analyses associated cardiovascular (odds ratios (OR) = 3.02, 95% confidence intervals (CI) = 1.23–7.39, p = 0.015), digestive (OR = 3.58, 95% CI = 1.01–12.63, p = 0.047), dementia (OR = 3.26, 95% CI = 1.26–8.41, p = 0.014), immunosuppressive (OR = 3.88, 95% CI = 1.34–11.21, p = 0.012) comorbidities with recurrences. Risk factor identification in the first episode of CDI could lead to the implementation of treatment strategies to improve the patients’ quality of life affected by this disease.

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RecurrentClostridium difficileInfection: Risk Factors, Treatment, and Prevention

Cited by 135 publications

References 98 publications

Healthcare resource utilization and direct medical costs associated with index and recurrent Clostridioides difficile infection: a real-world data analysis

Healthcare resource utilization and direct medical costs associated with index and recurrent Clostridioides difficile infection: a real-world data analysis

Impact of investigational microbiota therapeutic RBX2660 on the gut microbiome and resistome revealed by a placebo-controlled clinical trial

Risk Factors Associated with Recurrent Clostridioides difficile Infection

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