scholarly journals Protection from lethal Clostridioides difficile infection via intraspecies competition for co-germinant

2021 ◽  
Author(s):  
Jhansi L Leslie ◽  
Matthew L Jenior ◽  
Kimberly C Vendrov ◽  
Alex Standke ◽  
Madeline R Barron ◽  
...  
Keyword(s):  
Amino Acids ◽  
Virulent Strain ◽  
Single Species ◽  
Multiple Infection ◽  
Clostridioides Difficile ◽  
Nosocomial Diarrhea ◽  
Infection Models ◽  
Clostridioides Difficile Infection ◽  
Intraspecies Competition ◽  
Gut Microbial Community

Clostridioides difficile, a Gram-positive, spore-forming bacterium, is the primary cause of infectious nosocomial diarrhea. Antibiotics are a major risk factor for C. difficile infection (CDI) as they disrupt the gut microbial community, enabling increased germination of spores and growth of vegetative C. difficile. To date the only single-species bacterial preparation that has demonstrated efficacy in reducing recurrent CDI in humans is non-toxigenic C. difficile. Using multiple infection models we determined that pre-colonization with a less virulent strain is sufficient to protect from challenge with a lethal strain of C. difficile, surprisingly even in the absence of adaptive immunity. Additionally, we showed that protection is dependent on high levels of colonization by the less virulent strain and that it is mediated by exclusion of the invading strain. Our results suggest that reduction of amino acids, specifically glycine following colonization by the first strain of C. difficile is sufficient to decrease germination of the second strain thereby limiting colonization by the lethal strain.

scholarly journals Protection from Lethal Clostridioides difficile Infection via Intraspecies Competition for Cogerminant

mBio ◽  
2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Jhansi L. Leslie ◽  
Matthew L. Jenior ◽  
Kimberly C. Vendrov ◽  
Alexandra K. Standke ◽  
Madeline R. Barron ◽  
...  
Keyword(s):  
Virulent Strain ◽  
Single Species ◽  
Multiple Infection ◽  
Life Stages ◽  
Content Type ◽  
Clostridioides Difficile ◽  
Nosocomial Diarrhea ◽  
Clostridioides Difficile Infection ◽  
Intraspecies Competition ◽  
Gut Microbial Community

ABSTRACT Clostridioides difficile, a Gram-positive, spore-forming bacterium, is the primary cause of infectious nosocomial diarrhea. Antibiotics are a major risk factor for C. difficile infection (CDI), as they disrupt the gut microbial community, enabling increased germination of spores and growth of vegetative C. difficile. To date, the only single-species bacterial preparation that has demonstrated efficacy in reducing recurrent CDI in humans is nontoxigenic C. difficile. Using multiple infection models, we determined that precolonization with a less virulent strain is sufficient to protect from challenge with a lethal strain of C. difficile, surprisingly even in the absence of adaptive immunity. Additionally, we showed that protection is dependent on high levels of colonization by the less virulent strain and that it is mediated by exclusion of the invading strain. Our results suggest that reduction of amino acids, specifically glycine following colonization by the first strain of C. difficile, is sufficient to decrease germination of the second strain, thereby limiting colonization by the lethal strain. IMPORTANCE Antibiotic-associated colitis is often caused by infection with the bacterium Clostridioides difficile. In this study, we found that reduction of the amino acid glycine by precolonization with a less virulent strain of C. difficile is sufficient to decrease germination of a second strain. This finding demonstrates that the axis of competition for nutrients can include multiple life stages. This work is important, as it is the first to identify a possible mechanism through which precolonization with C. difficile, a current clinical therapy, provides protection from reinfection. Furthermore, our work suggests that targeting nutrients utilized by all life stages could be an improved strategy for bacterial therapeutics that aim to restore colonization resistance in the gut.

scholarly journals Risk Factors Associated with Recurrent Clostridioides difficile Infection

Healthcare ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 352
Author(s):  
Nicoleta Negrut ◽  
Simona Bungau ◽  
Tapan Behl ◽  
Shamim Ahmad Khan ◽  
Cosmin Mihai Vesa ◽  
...  
Keyword(s):  
Treatment Strategies ◽  
First Episode ◽  
Old Patients ◽  
Clostridioides Difficile ◽  
Nosocomial Diarrhea ◽  
Clostridioides Difficile Infection ◽  
Comorbidity Index ◽  
Diarrhea Syndrome ◽  
Multiple Episodes

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.

scholarly journals Initial vancomycin versus metronidazole for the treatment of first-episode non-severe Clostridioides difficile infection

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Kevin Zhang ◽  
Patricia Beckett ◽  
Salaheddin Abouanaser ◽  
Marek Smieja
Keyword(s):  
Treatment Guidelines ◽  
Multivariable Analysis ◽  
Current Treatment ◽  
Multivariate Logistic Regression Model ◽  
First Episode ◽  
Study Cohort ◽  
Clostridioides Difficile ◽  
Nosocomial Diarrhea ◽  
Clostridioides Difficile Infection ◽  
Incident Infection

Abstract Objective: Clostridioides difficile infection (CDI) is the leading cause of infectious nosocomial diarrhea. Although initial fidaxomicin or vancomycin treatment is recommended by most major guidelines to treat severe CDI, there exists varied recommendations for first-episode non-severe CDI. Given the discrepancy in current treatment guidelines, we sought to evaluate the use of initial vancomycin versus metronidazole for first-episode non-severe CDI. Methods: We conducted a retrospective cohort study of all adult inpatients with first-episode CDI at our institution from January 2013 to May 2018. The initial vancomycin versus initial metronidazole cohorts were examined using a multivariate logistic regression model. Results: The study cohort of 737 patients had a median age of 72.3 years, and 357 of these patients (48.4%) had hospital-acquired infection. Among 326 patients with non-severe CDI, recurrence, new incident infection, and 30-day mortality rates were 16.2%, 10.9%, and 5.3%, respectively, when treated with initial metronidazole, compared to 20.0%, 1.4%, and 10.0%, respectively, when treated with initial vancomycin. In an adjusted multivariable analysis, the use of initial vancomycin for the treatment of non-severe CDI was associated with a reduction in new incident infection (adjusted odds ratio [ORadj], 0.11; 95% confidence interval [CI], 0.02–0.86; P = .035), compared to initial metronidazole. Conclusions: Initial vancomycin was associated with a reduced rate of new incident infection in the treatment of adult inpatients with first-episode non-severe CDI. These findings support the use of initial vancomycin for all inpatients with CDI, when fidaxomicin is unavailable.

scholarly journals 2423. Cost-effectiveness of core and emerging infection control interventions to reduce hospital-onset Clostridioides difficile infection: An agent-based simulation modeling approach

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S837-S837
Author(s):  
Oguzhan Alagoz ◽  
Anna K Barker ◽  
Elizabeth Scaria ◽  
Nasia Safdar
Keyword(s):  
Cost Effectiveness ◽  
Hand Hygiene ◽  
Infection Control ◽  
Hospital Setting ◽  
Multiple Infection ◽  
Agent Based ◽  
Emerging Infection ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
The Cost

Abstract Background Multiple infection control interventions have been recommended to reduce hospital-onset Clostridioides difficile infection (C. difficile; HO-CDI), including contact isolation, environmental disinfection, and hand hygiene. These interventions have differential effects on reducing HO-CDI that change for each hospital setting. In the context of today’s constrained resources, with trade-offs a necessary part of any prevention plan, infection control personnel need information regarding intervention cost-effectiveness that is tailored to their unique hospital setting. Methods We evaluated the cost-effectiveness of nine infection control interventions and eight multiple-intervention bundles using our group’s agent-based model of C. difficile transmission. This previously developed model represents a general 200-bed acute-care adult hospital. Effectiveness was measured from the hospital perspective in terms of both quality-adjusted life years (QALYs) and HO-CDIs. Results Six interventions reduced cost while increasing QALYs and averting HO-CDI, compared with baseline standard hospital practices: daily cleaning (saved an average of $407,854 and 36.8 QALYs annually in a 200-bed hospital), HCW hand hygiene ($181,767; 17.7 QALYs), patient hand hygiene ($25,700; 6.3 QALYs), terminal cleaning ($64,986; 12.8 QALYs), screening at admission ($9,083; 18.5 QALYs), and reducing patient transfers ($27,514; 3.1 QALYs). Adding patient hand hygiene to the HCW hand hygiene intervention was cost saving. When screening, HCW hand hygiene, and patient hand hygiene interventions were sequentially added to daily cleaning to form two, three, and four-pronged bundles, the incremental cost-effectiveness ratios for these additions were $26,588, $44,173, and $123,379 per QALY, respectively. Conclusion Using cost-effectiveness data, institutions may consider streamlining their infection control initiatives and prioritizing a smaller number of highly effective interventions. Our model could be used to evaluate the cost-effectiveness of existing core and emerging infection control interventions for specific hospital settings. Disclosures All authors: No reported disclosures.

scholarly journals Risk factors and Intestinal Microbiota: Clostridioides difficile Infection in Patients Receiving Enteral Nutrition at Intensive Care Unit

2020 ◽  
Author(s):  
Daosheng Wang ◽  
Danfeng Dong ◽  
Chen Wang ◽  
Yingchao Cui ◽  
Cen Jiang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Intensive Care Unit ◽  
Intensive Care ◽  
Enteral Nutrition ◽  
Intestinal Microbiota ◽  
Intestinal Microbiome ◽  
Clostridioides Difficile ◽  
Nosocomial Diarrhea ◽  
Clostridioides Difficile Infection ◽  
Clinical Records

Abstract Background: Clostridioides difficile infection (CDI) is a leading cause of nosocomial diarrhea. Patients receiving enteral nutrition (EN) in the intensive care unit (ICU) are potentially at high risk of CDI. Presently, we assessed the risk factors and intestinal microbiome of these patients to better understand the occurrence and development of CDI. Methods: Patients were screened for C. difficile every week after EN started and their clinical records were collected for risk factor identification. Feces were analyzed for 16S rRNA sequencing to evaluate the intestinal microbiota. Results : Overall incidence of CDI was 10.7% (18/168 patients). History of cerebral infarction was associated with CDI occurrence (OR, 9.759; 95% CI, 2.140-44.498) and treatment with metronidazole could be protective (OR, 0.287; 95% CI, 0.091-0.902). Patients with EN had lower microbial richness and diversity, accompanied by reduced abundance of Bacteroides , Prevotella_9, Ruminococcaceae and Lachnospiraceae. Of these patients, acquisition of C. difficile resulted in a transient increase in microbial diversity, along with consistent alterations in the proportion of some bacterial taxa, especially Ruminococcaceae and Lachnospiraceae. At the initiation of EN, patients who were positive for C. difficile later had enhanced abundance of Bacteroides , which was negatively correlated with C. difficile load when CDI developed. Conclusion : ICU patients receiving EN had a high prevalence of CDI, and a fragile intestinal microbial environment. Alteration of microbiota composition could be vital in the process of CDI development, bringing new insights in the interaction between C. difficile and host microbiome.

scholarly journals 1211. Response to Fecal Microbiota Transplant (FMT) in Refractory Clostridioides difficile Infection (CDI) is Modest Compared to Recurrent CDI in Hospitalized Patients

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S627-S627
Author(s):  
Jae Hyun Shin ◽  
R Ann Hays ◽  
Cirle Warren
Keyword(s):  
Health System ◽  
Complete Resolution ◽  
Fecal Microbiota ◽  
Inpatient Setting ◽  
University Of Virginia ◽  
Cure Rate ◽  
Fecal Microbiota Transplant ◽  
Safety And Efficacy ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection

Abstract Background There are limited options for Clostridioides difficile infection (CDI) refractory to conventional antibiotic therapy (metronidazole, vancomycin, or fidaxomicin). Fecal microbiota transplant (FMT) is considered a safe and effective treatment for recurrent CDI but has not been widely utilized for refractory CDI due to concerns about safety. Even when included in studies, refractory CDI has not been analyzed separately from recurrent CDI. We reviewed cases of FMT performed in the inpatient setting for CDI to evaluate its safety and efficacy for refractory CDI. Methods Patients who received FMT inpatient at University of Virginia Health System for recurrent or refractory CDI after Infectious Diseases and Gastroenterology consultation signed informed consent acknowledging that FMT was considered investigational use in CDI not responding to standard of care as per 2014 FDA guidance. Charts were reviewed as part of quality improvement efforts to evaluate safety and efficacy of FMT in inpatient setting. Results Starting in July 2014, 13 patients received FMT for CDI as inpatients. Six received FMT for recurrent CDI, with four having complete resolution, one had recurrent CDI, and one had persistent C. difficile-negative diarrhea, for cure rate of 83%, comparable to published studies. Seven patients received FMT for refractory CDI, with three resulting in complete resolution. One responded to FMT but refused further care, one died from multiorgan failure after initial response to FMT that was possibly related to CDI, strongyloides, and/or CMV. Two patients had ongoing diarrhea suggestive of post-infectious irritable bowel syndrome, one was C. difficile-negative and one was not tested. The cure rate was 57%, lower than that of the recurrent CDI, but without any clear evidence of microbiologic failure. Outcome of patients undergoing FMT for CDI in the inpatient setting at University of Virginia Health System Conclusion Cure rate for FMT for refractory CDI was lower than recurrent CDI, but review of the cases of treatment failures did not reveal any microbiologic evidence of failure. FMT should be considered an alternative option when treating refractory CDI. Disclosures All Authors: No reported disclosures

scholarly journals Real-World Experience with Bezlotoxumab for Prevention of Recurrence of Clostridioides difficile Infection

2020 ◽  
Vol 10 (1) ◽  
pp. 2
Author(s):  
Rosa Escudero-Sánchez ◽  
María Ruíz-Ruizgómez ◽  
Jorge Fernández-Fradejas ◽  
Sergio García Fernández ◽  
María Olmedo Samperio ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Real World ◽  
Recurrence Rates ◽  
Factors Associated ◽  
Clostridioides Difficile ◽  
Multicentre Cohort Study ◽  
Clostridioides Difficile Infection ◽  
Prevention Of Recurrence ◽  
Multicentre Cohort

Bezlotoxumab is marketed for the prevention of recurrent Clostridioides difficile infection (rCDI). Its high cost could be determining its prescription to a different population than that represented in clinical trials. The objective of the study was to verify the effectiveness and safety of bezlotoxumab in preventing rCDI and to investigate factors related to bezlotoxumab failure in the real world. A retrospective, multicentre cohort study of patients treated with bezlotoxumab in Spain was conducted. We compared the characteristics of cohort patients with those of patients treated with bezlotoxumab in the pivotal MODIFY trials. We assessed recurrence rates 12 weeks after completion of treatment against C. difficile, and we analysed the factors associated with bezlotoxumab failure. Ninety-one patients were included in the study. The cohort presented with more risk factors for rCDI than the patients included in the MODIFY trials. Thirteen (14.2%) developed rCDI at 12 weeks of follow-up, and rCDI rates were numerically higher in patients with two or more previous episodes (25%) than in those who had fewer than two previous episodes of C. difficile infection (CDI) (10.4%); p = 0.09. There were no adverse effects attributable to bezlotoxumab. Despite being used in a more compromised population than that represented in clinical trials, we confirm the effectiveness of bezlotoxumab for the prevention of rCDI.

scholarly journals Clinical complications in patients with primary and recurrent Clostridioides difficile infection: A real-world data analysis

2021 ◽  
Vol 9 ◽  
pp. 205031212098673
Author(s):  
Paul Feuerstadt ◽  
Mena Boules ◽  
Laura Stong ◽  
David N Dahdal ◽  
Naomi C Sacks ◽  
...  
Keyword(s):  
Loop Ileostomy ◽  
Charlson Comorbidity Index Score ◽  
Real World Data ◽  
Infection Group ◽  
Bowel Surgery ◽  
Clinical Complications ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
Infection Episode

Objective: Clostridioides difficile infection and recurrent C. difficile infection result in substantial economic burden and healthcare resource use. Sepsis and bowel surgery are known to be serious complications of C. difficile infection. This study evaluated clinical complications in patients with C. difficile infection and recurrent C. difficile infection during a 12-month period following the primary C. difficile infection. Methods: A retrospective analysis of commercial claims data from the IQVIA PharMetrics Plus™ database was conducted for patients aged 18–64 years with an index C. difficile infection episode requiring inpatient stay or an outpatient visit for C. difficile infection followed by a C. difficile infection treatment. Each C. difficile infection episode ended after a 14-day C. difficile infection-claim-free period was observed. Recurrent C. difficile infection was defined as a further C. difficile infection episode within an 8-week window following the claim-free period. Clinical complications were documented over 12 months of follow-up and stratified by the number of recurrent C. difficile infection episodes (0 rCDI, 1 rCDI, 2 rCDI, and 3+ rCDI). Results: In total, 46,571 patients with index C. difficile infection episode were included. During the 6-month pre-index, the mean (standard deviation) baseline Charlson comorbidity index score, by increasing the recurrent C. difficile infection group, was 1.2 (1.9), 1.5 (2.2), 1.8 (2.3), and 2.3 (2.5). During the 12-month follow-up, sepsis occurred in 16.5%, 27.3%, 33.1%, and 43.3% of patients, and subtotal colectomy or diverting loop ileostomy was performed in 4.6%, 7.3%, 8.9%, and 10.5% of patients, respectively, by increasing the recurrent C. difficile infection group. Conclusions: Reduction in recurrent C. difficile infection is an important step to reduce the burden of serious clinical complications, and new treatments are needed to reduce C. difficile infection recurrence.

scholarly journals Analysis of National Healthcare Safety Network Clostridioides difficile Infection Standardized Infection Ratio by Test Type

2020 ◽  
Vol 41 (S1) ◽  
pp. s116-s118
Author(s):  
Qunna Li ◽  
Andrea Benin ◽  
Alice Guh ◽  
Margaret A. Dudeck ◽  
Katherine Allen-Bridson ◽  
...  
Keyword(s):  
Risk Adjustment ◽  
Healthcare Facility ◽  
Directional Pattern ◽  
Incidence Rates ◽  
Nucleic Acid Amplification ◽  
Test Type ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
The Mean ◽  
The Difference

Background: The NHSN has used positive laboratory tests for surveillance of Clostridioides difficile infection (CDI) LabID events since 2009. Typically, CDIs are detected using enzyme immunoassays (EIAs), nucleic acid amplification tests (NAATs), or various test combinations. The NHSN uses a risk-adjusted, standardized infection ratio (SIR) to assess healthcare facility-onset (HO) CDI. Despite including test type in the risk adjustment, some hospital personnel and other stakeholders are concerned that NAAT use is associated with higher SIRs than are EIAs. To investigate this issue, we analyzed NHSN data from acute-care hospitals for July 1, 2017 through June 30, 2018. Methods: Calendar quarters for which CDI test type was reported as NAAT (includes NAAT, glutamate dehydrogenase (GDH)+NAAT and GDH+EIA followed by NAAT if discrepant) or EIA (includes EIA and GDH+EIA) were selected. HO CDI SIRs were calculated for facility-wide inpatient locations. We conducted the following analyses: (1) Among hospitals that did not switch their test type, we compared the distribution of HO incident rates and SIRs by those reporting NAAT vs EIA. (2) Among hospitals that switched their test type, we selected quarters with a stable switch pattern of 2 consecutive quarters of each of EIA and NAAT (categorized as pattern EIA-to-NAAT or NAAT-to-EIA). Pooled semiannual SIRs for EIA and NAAT were calculated, and a paired t test was used to evaluate the difference of SIRs by switch pattern. Results: Most hospitals did not switch test types (3,242, 89%), and 2,872 (89%) reported sufficient data to calculate SIRs, with 2,444 (85%) using NAAT. The crude pooled HO CDI incidence rates for hospitals using EIA clustered at the lower end of the histogram versus rates for NAAT (Fig. 1). The SIR distributions of both NAAT and EIA overlapped substantially and covered a similar range of SIR values (Fig. 1). Among hospitals with a switch pattern, hospitals were equally likely to have an increase or decrease in their SIR (Fig. 2). The mean SIR difference for the 42 hospitals switching from EIA to NAAT was 0.048 (95% CI, −0.189 to 0.284; P = .688). The mean SIR difference for the 26 hospitals switching from NAAT to EIA was 0.162 (95% CI, −0.048 to 0.371; P = .124). Conclusions: The pattern of SIR distributions of both NAAT and EIA substantiate the soundness of NHSN risk adjustment for CDI test types. Switching test type did not produce a consistent directional pattern in SIR that was statistically significant.Disclosures: NoneFunding: None

Sign in / Sign up

Export Citation Format

Share Document