scholarly journals 761. Host Intestinal Defenses Against Clostridioides difficile Infection in Chemotherapy Patients

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S478-S478
Author(s):  
Claire Weinstein ◽  
Racheal Wilkinson ◽  
Senu Apewokin
Keyword(s):  
Cancer Treatment ◽  
Stool Sample ◽  
Protective Factor ◽  
Intestinal Flora ◽  
Paneth Cells ◽  
Clostridioides Difficile ◽  
Response To Chemotherapy ◽  
Clostridioides Difficile Infection ◽  
Lysozyme Concentration ◽  
Chemotherapy Patients

Abstract Background Clostridioides difficile infection (CDI) is a common complication in patients undergoing cancer treatment with cytotoxic chemotherapy. Exposure to antibiotics or chemotherapy disrupts the microbiome by killing protective intestinal flora which consequently promotes C. difficile spore germination and disease. The host defense against CDI includes colonization resistance conferred by the healthy microbiome and innate defenses provided by intestinal epithelial cells. One protective factor secreted by Paneth cells of the intestinal epithelium is lysozyme, an enzyme that degrades the cell walls of Gram-positive bacteria such as C. difficile. We hypothesized that chemotherapy-induced mucosal barrier injury and the resultant death of Paneth cells leads to decreased production of lysozyme. We thus sought to examine changes in lysozyme concentration in stools of chemotherapy patients. Methods We collected stool samples from six patients undergoing cancer treatment at four different time points. The first stool sample corresponded to the day prior to the start of chemotherapy (day zero). We then performed ELISA assays to determine the lysozyme concentration for each stool sample. Results On day zero, the lysozyme levels (n=6) averaged 268.1 ± 131.7 ng/mL. Over the course of chemotherapy, the lysozyme levels decreased 78.70 ± 24.19% from the starting value. The lowest values were observed around days 5 through 11 for most patients, coinciding with when they were most neutropenic around day 11. One of the patients developed CDI on day 5 and experienced more fluctuating lysozyme levels thereafter. On the day that the patient developed CDI, lysozyme was measured as 6.63 ng/mL. Throughout treatment, 3/6 patients showed recovery of lysozyme production with white blood cell recovery. Conclusion Our data indicate that chemotherapy causes decreased concentrations of lysozyme in stool. Low lysozyme levels could in part account for the increased susceptibility to CDI during chemotherapy. Future experiments will include bioinformatics analyses to determine how the microbiome changes in response to chemotherapy. Together, these experiments will inform our approach to determining patient susceptibility to chemotherapy-associated CDI. Disclosures All Authors: No reported disclosures

scholarly journals 1376. Oral Vancomycin as Secondary Prophylaxis Against Clostridioides difficile Infection in Pediatric Patients

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S698-S698
Author(s):  
Hongkai Bao ◽  
Yanina Dubrovskaya ◽  
John Papadopoulos ◽  
Justin Siegfried ◽  
Cristian Merchan ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Odds Ratio ◽  
Protective Factor ◽  
Pediatric Patients ◽  
Antibiotic Exposure ◽  
Oral Vancomycin ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
History Of ◽  
Systemic Antibiotics

Abstract Background Secondary oral vancomycin prophylaxis (OVP) has been utilized in adults with a history of Clostridioides difficile infection (CDI) while receiving systemic antibiotics to prevent CDI recurrence. However, this practice is poorly described in pediatric patients. Rates of CDI recurrence in pediatric patients range from 10-40% and is associated with morbidity and mortality. This study assessed the efficacy and safety of secondary OVP in pediatric patients with subsequent antibiotic exposure. Methods This retrospective study evaluated pediatric patients ≤18 years with any history of clinical CDI and receiving systemic antibiotics in a subsequent encounter during the time period of 2013-2019. Patients who received OVP 10 mg/kg (up to 125 mg per dose) every 12 hours during concomitant antibiotics were compared to those who did not. The primary outcome was CDI recurrence within 8 weeks following antibiotic exposure. Secondary outcomes included time to recurrence, severity of recurrence, and isolation of vancomycin-resistant enterococci (VRE) from any site. Risk factors for CDI recurrence were assessed using logistic regression. Results A total of 153 patients were screened for inclusion, of which 32 and 47 patients were assigned to the OVP and no OVP group, respectively. Median age was 8.6 years and the most common comorbidities were malignancy (47%) and immunosuppression (46%). Median time since last CDI to study inclusion was 64.5 days in the OVP group and 90 days in the no OVP group, P=0.320. Compared to the no OVP group, OVP patients had longer hospital stays (5 vs 14 days, P=0.001) and more concomitant antibiotic exposure (8 vs 12.5 days, P=0.001). Median duration of OVP was 12 days. CDI recurrence occurred in 12 patients and was significantly lower in the OVP vs no OVP group (3.1% vs 23.4%; odds ratio, 0.106; 95% confidence interval, 0.013-0.864; P=0.022). VRE was not isolated in any patients. After adjustment in a multivariate analysis, only secondary OVP remained as a protective factor against recurrence (odds ratio, 0.082; 95% confidence interval, 0.009-0.748; P=0.027). Conclusion Secondary OVP effectively reduces the risk of recurrent CDI in pediatric patients with a history of CDI while receiving systemic antibiotics. Future prospective studies should validate these findings. Disclosures Cristian Merchan, PharMD, BCCCP, abbive (Speaker’s Bureau)

scholarly journals Romanian National Guideline on Translating Fecal Microbiota Transplantation Applications related to Clostridioides difficile Infections into the Local Clinical Practice

2021 ◽  
Vol 30 (1) ◽  
pp. 147-163
Author(s):  
Georgiana Emmanuela Gilca-Blanariu ◽  
Gabriela Stefanescu ◽  
Irina Girleanu ◽  
Tariq Iqbal ◽  
Jonathan Segal ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Fecal Microbiota Transplantation ◽  
Scientific Evidence ◽  
Intestinal Flora ◽  
Fecal Microbiota ◽  
National Guideline ◽  
Fecal Transplant ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
Working Groups

Fecal microbiota transplantation involves the infusion of intestinal microorganisms via the transfer of a stool from a healthy individual into a diseased individual, with the intent of restoring normal intestinal flora. Fecal transplant is proposed for the treatment of refractory Clostridioides difficile infection. At present, recurrent Clostridioides difficile infection is the only indication supported by solid scientific evidence. Regulations by healthcare authorities vary among different countries. Considering that Romania does not have an available national guideline to offer standardization, this paper aimed to create a national fecal microbiota transplantation guideline concerning indications, techniques and donor screening, developed by international and local scientific working groups.

scholarly journals Successful use of early, repeat fecal microbiota transplantation for initial treatment of severe, refractory Clostridioides difficile colitis

2021 ◽  
Author(s):  
Catherine M Cappetto
Keyword(s):  
Stool Sample ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Community Dwelling ◽  
Nutrition Status ◽  
Vancomycin Therapy ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
Polymerase Chain ◽  
Initial Episode

Abstract Disclaimer In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose There is a paucity of literature surrounding the use of early fecal microbiota transplantation (FMT) for patients presenting with an initial episode of severe, refractory Clostridioides difficile infection (CDI). Information on optimal antibiotic dosing and therapy duration surrounding FMT during an acute, initial episode of CDI is also limited. Described here is a case of successful treatment of CDI after 4 FMTs during an acute, initial episode of severe, refractory Clostridioides difficile colitis. Summary A 69-year-old community-dwelling, Caucasian male presented after 48 hours of vomiting and diarrhea. A stool sample tested positive via stool sample by both polymerase chain reaction and enzme-linked immunosorbent assays for Clostridioides difficile. The patient was treated with several days of oral and rectal vancomycin therapy in addition to intravenous metronidazole, but those treatments failed. His clinical and nutrition status deteriorated over the course of several days until salvage therapy was ordered, with administration of 1 inpatient nasogastric FMT and 1 inpatient colonoscopic FMT followed by outpatient colonoscopic FMTs on 2 consecutive days within 2 weeks of hospital discharge. Conclusion This case suggests a role for early, repeat FMT during an initial presentation of a severe Clostridioides difficile colitis episode refractory to pharmacologic antimicrobial therapy. It also adds to emerging literature regarding the timing of antibiotic cessation surrounding FMT.

scholarly journals РОЗРОБКА CЕЛЕКТИВНОГО СЕРЕДОВИЩА ДЛЯ ВИДІЛЕННЯ ТОКСИН ПРОДУКУЮЧИХ ШТАМІВ C. DIFFICILE

World Science ◽  
2020 ◽  
Author(s):  
Said Kheder
Keyword(s):  
Nutrient Medium ◽  
Intestinal Flora ◽  
High Growth ◽  
Chemotherapeutic Agents ◽  
Economic Losses ◽  
Etiologic Factor ◽  
Clostridioides Difficile ◽  
Antibiotic Associated Diarrhea ◽  
Growth Properties ◽  
Clostridioides Difficile Infection

Enterocolitis disorders caused by Clostridioides difficile infection still remain a serious health problem in the world. In many countries CDI is officially considered a nosocomial infection that causes considerable economic losses, including diagnostic and treatment costs. According to the existing data, C. difficile is the main agent causing antibiotic – associated diarrhea and the main etiologic factor of the pseudomembranous colitis (PMC) that often develops in case of complete destruction of the intestinal flora due to the use of antibiotics or chemotherapeutic agents. There is no official registration of CDI in Ukraine, therefore the official incidence and lethality rates are absent. At this time, the problems of development and improvement of selective nutrient mediums and quick, affordable bacteriological methods of C. difficile isolation are especially relevant.The comparative study of the efficacy of the known commercial nutrient mediums for isolation of toxin-producing strains of C. difficile was carried out and composition of a new, original selective nutrient medium was proposed. Unlike existing analogs, the proposed nutrient medium is suitable for the simultaneous isolation of the agent from the clinical material and detection of toxin-producing properties due to its high growth properties, optimal transparency and density.

scholarly journals Risk factors for Clostridioides difficile infection and colonization among patients admitted to intensive care units  in Shanghai, China

2019 ◽  
Author(s):  
Yingchao Cui ◽  
Danfeng Dong ◽  
Lihua Zhang ◽  
Daosheng Wang ◽  
Cen Jiang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Intensive Care ◽  
Intensive Care Units ◽  
Protective Factor ◽  
Epidemic Clone ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
Hospital Stays ◽  
And Control ◽  
Epidemiological Characteristics

Abstract Background : Clostridioides difficile is considered to be the main pathogen responsible for hospital-acquired infections. This study performed a prospective study to describe the prevalence, molecular epidemiological characteristics and risk factors of Clostridioides difficile infection (CDI) and Clostridioides difficile colonization (CDC) among patients in intensive care units (ICUs), a tertiary hospital in China, with the aim of providing strategies for efficient CD prevention and control. Methods: Stool samples were collected and anaerobically cultured for C. difficile . The identified isolates were tested for toxin genes and multi-locus sequence typing. The medical records of patients who were divided into CDI, CDC and control groups were collected and analyzed to investigate the risk factors. Results: Of the 800 patients included in the study, 33 (4.12%) and 25 (3.12%) patients were identified with CDI and CDC, respectively. An association was found between CDI patients and having a fever (OR=13.993) or metabolic disorder (OR=7.972), and treatment with fluoroquinolone (OR=42.696) or a combination of antibiotics (OR=2.856). CDC patients were characterized by longer hospital stays (OR=1.137), an increased number of comorbidities (OR=36.509), respiratory diseases (OR=0.043) and treatment with vancomycin (OR=18.168). Significantly, treatment with metronidazole was simultaneously found to be a protective factor in the two groups (OR=0.042; OR=0.013). Eighteen sequence types (STs) were identified. Among the CDI group, the isolates were predominantly toxin A and toxin B positive (A+B+) strains and genotype ST2 was the epidemic clone. In the CDC group, the dominant strains were A+B+ and ST81 was the epidemic clone. Conclusions: The prevalence of CDC and CDI in our ICUs was relatively high, suggesting the importance of routine screening to detect the acquisition of this pathogen. Future prevention and treatment strategies for C. difficile -related disease should consider hospital stays, enteral nutrition, underlying comorbidities, and the use of combined antibiotics. Moreover, metronidazole could be a protective factor for both CDI and CDC, which could be used empirically .

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

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