Clostridioides Difficile Infection Rates Research Articles

180. Impact of a two-step diagnostic bundle on hospital-onset Clostridioides difficile infection rates and treatment across a large health system.

Abstract Background Distinguishing true Clostridioides difficile Infection (CDI) from colonization is a challenge, with nearly 20% of hospitalized adults being carriers of C. difficile. Polymerase chain reaction (PCR) testing alone is not able to distinguish colonization from infection, leading to over-diagnosis and unnecessary treatment. Despite interventions including pre-approval by antimicrobial stewardship programs (ASP), reportable hospital-onset CDI (HO-CDI) rates across our health system remained high. In 2021, we implemented a C. difficile PCR with reflex toxin enzyme immunoassay (EIA) testing strategy to improve diagnostic accuracy and treatment outcomes. The purpose of this study was to evaluate the impact of this two-step testing algorithm bundled with education, ASP support and order set changes on HO-CDI rates and C. difficile treatment across our health system. Methods PCR with EIA testing algorithm was implemented between May and August 2021 across seven hospitals within the Northwestern Medicine Health System. Multifaceted education was delivered to leadership and clinicians in person and electronically to. ASP performed daily diagnostic prospective audit and management support. Clinical decision support (CDS) was incorporated into order sets to promote diagnostic stewardship (Table 1, Figure 1). Standardization of analyst-developed tracking reports allowed for longitudinal monitoring across the system and at each facility, including unit- and patient-level data. Figure 1C. Difficile Testing Algorithm PCR/Reflex Toxin EIA Results The HO-CDI standardized infection ratio (SIR) reduced significantly from 0.8 to 0.57 p< 0.001), and reportable HO-CDI cases reduced by 238 cases across the health system between May 2021 and March 2022. 6043 samples were tested, of which 282 (4.7%) were confirmed CDI cases (PCR+/toxin+) and 687 (11%) were non-CDI cases (PCR+/toxin-), of which 438 (67%) received CDI treatment. (Figure 2 and 3). Figure 3 Actual versus avoided HO C. difficile cases. Conclusion The two-step CDI diagnostic and treatment bundle significantly reduced the SIR of HO-CDI. Although treatment of colonized patients remained high, a large number of patients safely avoided CDI treatment. Testing and education bundles can help advance antimicrobial and diagnostic stewardship by improving detection, treatment, and tracking of CDI. Disclosures Asra Salim, MPH, CPH, FAPIC, IRhythym Technologies Inc: Stocks/Bonds.

Lack of correlation between standardized antimicrobial administration ratios (SAARs) and healthcare-facility-onset Clostridioides difficile infection rates in Veterans Affairs medical facilities.

We detected no correlation between standardized antimicrobial administration ratios (SAARs) and healthcare facility-onset Clostridioides difficile infection (HO-CDI) rates in 102 acute-care Veterans Affairs medical centers over 16 months. SAARs may be useful for investigating trends in local antimicrobial use, but no ratio threshold demarcated HO-CDI risk.

Molecular epidemiology and clinical characteristics of Clostridioides difficile infection in patients with inflammatory bowel disease from a teaching hospital.

Clostridioides difficile infection (CDI) in patients with inflammatory bowel disease (IBD) is of increasing concern. This study aimed to investigate the molecular epidemiology and antimicrobial susceptibilities of toxigenic C. difficile isolated from IBD patients and to evaluate the risk factors for CDI in IBD population. Loose or watery stools from IBD patients were tested for glutamate dehydrogenase, C. difficile toxins A&B and anaerobic culture. Toxigenic C. difficile isolates were characterized by multi-locus sequence typing, ribotyping and antimicrobial susceptibility testing. The prevalence of CDI in IBD patients was 13.6% (43/317). The dominant sequence types (STs) were ST35 (20.9%), ST2 (18.6%) and ST37 (16.3%). The most common ribotypes (RTs) were RT 017 (18.6%), RT 012 (14.0%), and RT 220 (14.0%), whereas RT 027 and RT 078 were not detected in this study. All the isolates were susceptible to vancomycin and metronidazole. The multidrug resistance rate of C. difficile RT 017 was higher (p < 0.01) than that of other RT strains. Recent hospitalization, use of corticosteroids and proton pump inhibitors were related to increased risk of CDI in IBD patients; of these, recent hospitalization and proton pump inhibitors use were independent risk factors. Patients with IBD have a relatively high incidence rate of CDI. C. difficile RT 017 is most frequently isolated from IBD patients in this region and warrants more attention to its high resistance rate. Clinicians should pay greater attention to CDI testing in IBD patients with diarrhea to ensure early diagnosis and initiation of effective treatment.

Trends and Disparities in Outcomes of Clostridioides difficile Infection Hospitalizations in the United States: A Ten-Year Joinpoint Trend Analysis.

Clostridioides difficile infection (CDI) is the most frequently reported nosocomial infection. This study aimed to describe epidemiological trends, sex, race, and economic disparities in clinical and mortality outcomes among CDI hospitalizations over a decade. We queried Nationwide Inpatient Sample databases from 2010 to 2019, identified hospitalizations with CDI, and obtained the incidence and admission rate of CDI per 100,000 adult hospitalizations each year. We analyzed trends in mortality rate, mean length of hospital stay (LOS), and mean total hospital charge (THC). We highlighted disparities in outcomes stratified by sex, race, and mean household income quartile. Of the 305 million hospitalizations included in our study, over 3.3 million were complicated by CDI, with 1.01 million principal admissions for CDI. Among primary admissions for CDI, the mortality rate decreased from 3.2% in 2010 to 1.4% in 2019. Mean LOS reduced from 6.6 to 5.3 days while mean THC increased from US$40,593 to US$42,934 between 2010 and 2019. Females had a 21% decrease in adjusted odds of mortality compared to males (all P-trends < 0.001). Middle-aged and elderly patients had aOR of 4.96 and 14.74 respectively for mortality when compared to young adults (P < 0.001). Mortality rates showed a steady decline among Whites over the study period. Mean LOS trends were similar across racial subgroups. Outcomes of CDI hospitalizations improved over the studied decade. Older age, male sex, and being from a minority racial group were associated with worse clinical and mortality outcomes. Further studies are needed to elucidate the reasons for these findings.

S197 Real Word Experience of Bezlotoxumab for the Prevention of Recurrent Clostridioides difficile Infection: A Systematic Review and Meta-analysis

Introduction: Two large, placebo-controlled phase III trials, MODIFY I and MODIFY II, demonstrated that patients with Clostridioides difficile infection (CDI) treated with bezlotoxumab (BEZ) had a lower rate of recurrent infection than placebo. The clinical efficacy of BEZ has been evaluated in real-world studies. We aimed to carry out a systematic review and meta-analysis of the efficacy of BEZ in real-world clinical setting. Methods: A thorough search of literature was run on February 2022, in Cochrane Central Register of Controlled Trials, Embase, Medline, Scopus and Web of Science Core Collection. We included studies that reported CDI resolution rates with BEZ. The random-effects model described by DerSimonian and Laird was used to calculate weighted pooled resolution rates (WPR) with corresponding 95% confidence intervals (CI). Data were weighted based on the sample size in each trial to calculate WPR. We assessed heterogeneity within groups with the inconsistency index (I2) statistic. The primary outcome of our pooled analysis was CDI clinical resolution rates with BEZ i.e. resolution of CDI with no recurrence in the follow up period. Results: Thirteen studies (11 retrospective cohorts, 2 unspecified) including 1008 CDI patients were included. Recurrence with BEZ was compared with standard-of-care (SOC) antibiotics (metronidazole, vancomycin or fidaxomicin) in 6 studies and with fecal microbiota transplantation (FMT) in 1 study, the other 6 had no comparator arm. A total of 771 patients received BEZ, 237 received SOC and 14 received FMT. Patients were followed for recurrence for a median of 90 days from initial episode (range 84-168 days). Of the 771 on BEZ, 550 had CDI resolution with WPR of 82% (95% CI 79-85%). No significant heterogeneity was noted, with I2=0% (Figure). A resolution rate of 50% (7/14) was seen in the FMT group. Subgroup analysis comparing BEZ with SOC revealed a WPR of 84% (95% CI 79-89%) with BEZ vs 67% (95% CI 61-73%) with SOC (p=0.0001). Conclusion: Use of BEZ in real-world clinical settings seems to have a high resolution rate of CDI in patients with recurrence.Figure 1.: Forest plot depicting weighted resolution rate observed with bezlotoxumab

Prevalence and trends of Clostridioides difficile infection among persons requiring maintenance hemodialysis: A systematic review and meta-analysis.

Clostridioides difficile infection (CDI) is among the most common cause of healthcare-associated infections. Persons requiring maintenance hemodialysis (MHD) are at increased risk of CDI and associated mortality compared to persons not requiring MHD. Given the clinical impact of CDI among persons requiring MHD, we aimed to quantify the burden of CDI and trends over time in this patient population. A systematic review and meta-analysis of studies reporting rates of CDI among persons requiring MHD in MEDLINE, Embase, Web of Science Core Collection, CINAHL, and Cochrane Central Register of Controlled Trials were performed. Searches were conducted on May 17, 2021, and March 4, 2022. In total, 2,408 titles and abstracts were identified; 240 underwent full text review. Among them, 15 studies provided data on rates of CDI among persons requiring MHD, and 8 of these also provided rates among persons not requiring MHD. The pooled prevalence of CDI among persons requiring MHD was 19.14%, compared to 5.16% among persons not requiring MHD (odds ratio [OR], 4.35; 95% confidence interval [CI], 2.07-9.16; P = .47). The linear increase in CDI over time was significant, increasing an average of 31.97% annually between 1993 and 2017 (OR, 1.32; 95% CI, 1.1-1.58; P < .01). The linear annual increase was similar among persons requiring and not requiring MHD (OR, 1.28; 95% CI, 1.13-1.45; P = .11). Persons requiring MHD have a 4-fold higher risk of CDI compared to persons not requiring MHD, and rates of CDI are increasing over time in both groups.

Intestinal Dysbiosis and Risk of Posttransplant Clostridioides difficile Infection in a Longitudinal Cohort of Liver Transplant Recipients.

ABSTRACTClostridioides difficile infection (CDI) has a higher incidence in solid organ transplant recipients than other hospitalized patients and can lead to poor outcomes. Perturbations to the intestinal microbiome are common in patients undergoing liver transplant (LT); however, the impacts of microbial diversity and composition on risk of CDI in this patient population is incompletely understood. Here, we assessed patients in an established, longitudinal LT cohort for development of CDI within 1 year of transplant. Clinical data were compared for patients with and without CDI using univariable models. 16S rRNA sequencing of fecal samples was performed at multiple pre- and posttransplant time points to compare microbiome α- and β-diversity and enrichment of specific taxa in patients with and without CDI. Of 197 patients who underwent LT, 18 (9.1%) developed CDI within 1 year. Pre-LT Child-Pugh class C liver disease, postoperative biliary leak, and use of broad-spectrum antibiotics were significantly associated with CDI. Patients who developed CDI had significantly lower α-diversity than patients without CDI overall and in samples collected at months 1, 3, and 6. Microbial composition (β-diversity) differed between patients with and without CDI and across sampling time points, particularly later in their posttransplant course. We also identified 15 (8%) patients with toxigenic C. difficile colonization who did not develop CDI and may have had additional protective factors. In summary, clinical and microbiome factors are likely to converge to impart CDI risk. Along with enhanced preventive measures, there may be a role for microbiome modulation to restore microbial diversity in high-risk LT patients.IMPORTANCE Liver transplant (LT) recipients have high rates of Clostridioides difficile infection (CDI), which has been associated with poor outcomes, including graft-related complications and mortality, in prior studies. Susceptibility to CDI is known to increase following perturbations in intestinal commensal bacteria that enable germination of C. difficile spores and bacterial overgrowth. In LT patients, changes in the intestinal microbiome resulting from advanced liver disease, surgery, and other clinical factors is common and most pronounced during the early posttransplant period. However, the relationship between microbiome changes and CDI risk after LT remains unclear. In this study, we investigated clinical and microbiome factors associated with development of CDI within the first year after LT. The importance of this work is to identify patients with high-risk features that should receive enhanced preventive measures and may benefit from the study of novel strategies to reconstitute the intestinal microbiome after LT.

Epidemiology of Clostridium (Clostridioides) difficile Infection in Southeast Asia.

This review describes the current understanding of Clostridium (Clostridioides) difficile infection (CDI) in southeast Asia regarding the prevalence of CDI, C. difficile detection methods, antimicrobial susceptibility profiles, and the potential significance of a One Health approach to prevention and control. Our initial focus had been the Indochina region, however, due to limited studies/surveillance of CDI in Indochina, other studies in southeast Asian countries and neighboring Chinese provinces are presented here for comparison. Clostridium (Clostridioides) difficile infection is one of the most common causes of hospital-acquired gastroenteritis worldwide. Since its discovery as a cause of pseudomembranous colitis in 1978, C. difficile-related disease has been more prevalent in high-income rather than low-income countries. This may be because of a lack of knowledge and awareness about the significance of C. difficile and CDI, resulting in underreporting of true rates. Moreover, the abuse of antimicrobials and paucity of education regarding appropriate usage remain important driving factors in the evolution of CDI worldwide. The combination of underreporting of true CDI rates, along with continued misuse of antimicrobial agents, poses an alarming threat for regions like Indochina. C. difficile ribotype (RT) 027 has caused outbreaks in North America and European countries, however, C. difficile RT 017 commonly occurs in Asia. Toxin A-negative/toxin B-positive (A-B+) strains of RT 017 have circulated widely and caused outbreaks throughout the world and, in southeast Asia, this strain is endemic.

The evaluation of fecal microbiota transplantation vs vancomycin in a Clostridioides difficile infection model.

Vancomycin is the preferred treatment for Clostridioides difficile infection (CDI) but has been associated with a high recurrence rate of CDI in treated patients. Fecal microbiota transplantation (FMT) has emerged as a remarkably successful treatment for recurrent CDI (rCDI). Herein, we present a mouse model of CDI to further define the changes in intestinal inflammation, flora, and metabolites following FMT versus vancomycin treatment and to find the potential therapy to restore colonization resistance. Both FMT and vancomycin treatment could ameliorate CDI-induced clinical features and intestinal tissue damage, with decrease in the levels of inflammatory mediators like IL-1β, IL-6, TNF-α, G-CSF, and MCP-1 in the colon and plasma. Observing the fecal gut microbiome profile revealed that unlike vancomycin, FMT could replenish intestinal microbiota by augmenting the relative abundance of the phylum Bacteroidetes and eliminating the abundance of the phylum Proteobacteria. FMT also reduced the levels of several carbohydrates, such as raffinose and fructose-6-phosphate, and amino acids, including tryptophan and glutamyl-valine, in the gut metabolome, thus suppressing C. difficile germination and growth. Our results suggest that the FMT-induced reconstruction of a specific gut community structure and restoration of metabolites promote the recovery of colonization resistance in mice better than vancomycin, thus offering new insights for the prevention of rCDI. KEY POINTS: • Both FMT and vancomycin ameliorate CDI-induced inflammatory response. • FMT restores a specific community structure and gut metabolites. • Mice treated with FMT may promote the recovery of colonization resistance and has a better outcome.

Fidaxomicin Use in the Pediatric Population with Clostridioides difficile.

Clostridioides difficile infection (CDI) remains a devastating infection both in hospital settings and in the community. While a number of antibiotics have anti-C. difficile activity, fidaxomicin is unique as a minimally absorbed antibiotic with narrow spectrum of activity. These features make it an appealing option for pediatric CDI to balance safety and efficacy. The purpose of this structured review was to outline the clinical evidence for safety and efficacy of fidaxomicin for pediatric CDI. A structured literature search was performed to identify relevant clinical data. Fidaxomicin is similarly effective to oral vancomycin with a lower rate of recurrent CDI. There were no serious safety signals reported with fidaxomicin. In conclusion, fidaxomicin is a safe and effective treatment option for pediatric CDI.

Whole-genome sequencing links Clostridium (Clostridioides) difficile in a single hospital to diverse environmental sources in the community.

To investigate if Clostridium (Clostridioides) difficile infection (CDI), traditionally thought of as hospital-acquired, can be genomically linked to hospital or community environmental sources, and to define possible importation routes from the community to the hospital. In 2019, C.difficile was isolated from 89/300 (29.7%) floor and 96/300 (32.0%) shoe sole samples at a tertiary hospital in Western Australia. Non-toxigenic C.difficile ribotype (RT) 010 predominated among floor (96.6%) and shoe sole (73.2%) isolates, while toxigenic RT 014/020 was most prevalent among contemporaneous clinical cases (33.0%) at the hospital. Whole-genome sequencing and high-resolution core genome single nucleotide polymorphism (cgSNP) analysis on C.difficile strains from hospital and community sources showed no clinical C.difficile RT 014/020 strains were genetically related, and evidence of frequent long-distance, multi-directional spread between humans, animals and the environment. In addition, cgSNP analysis of environmental RT 010 strains suggested transportation of C.difficile via shoe soles. While C.difficile RT 014/020 appears to spread via routes outside the healthcare system, RT 010 displayed a pattern of possible importation from the community into the hospital. These findings suggest developing community-based infection prevention and control strategies could significantly lower rates of CDI in the hospital setting.

Ceftriaxone versus ampicillin for the treatment of community-acquired pneumonia. A propensity matched cohort study

ObjectivesCeftriaxone is recommended as first-line antibiotic treatment (with the addition of macrolide) for hospitalised adults with community acquired pneumonia (CAP). Narrower-spectrum β-lactam as ampicillin, may be associated with comparable clinical outcomes, with less emergence of resistant pathogens or Clostridioides difficile infection (CDI). We aimed to examine whether ampicillin and ceftriaxone (with the addition of macrolides for both arms) are comparable for the treatment of hospitalized adults due to CAP. MethodsThis was a single center, observational cohort study. We included adult patients who were hospitalized in internal medicine wards due to CAP and were treated with either ceftriaxone or ampicillin with the addition of macrolide. A propensity-score model was used. The primary outcome was 30-day all-cause mortality. A multivariable logistic regression analysis and Kaplan-Meier survival analysis was performed. We performed subgroup analyses for the main outcome based on CURB-65 score and age. ResultsA total of 1586 patients fulfilled the inclusion criteria. There was no difference in 30-day mortality rate in the total cohort (28/233 vs. 208/1353 in ampicillin and ceftriaxone arm, respectively; p = 0.184). In the propensity matched cohort (197 in ampicillin and 394 in ceftriaxone arm), there was no significant difference in 30-day all-cause mortality between treatment groups in multivariable analysis of the main model (OR 0.67, 95% CI, 0.37–1.2; p = 0.189) and Kaplan-Meier survival analysis (p = 0.108). Thirty-day mortality rate was (19/197 vs. 57/394, in ampicillin and ceftriaxone arms, respectively; p = 0.108) Patients who were treated with ampicillin experienced significantly lower rates of CDI (0/197, 0% vs. 8/394, 2%; p = 0.044). DiscussionAmpicillin was associated with comparable clinical outcomes in comparison to ceftriaxone for patients who were hospitalized due to CAP. Ampicillin was associated with significantly lower rate of CDI. Results need to be confirmed by more robust study designs.

Association between consumption of antibiotics, infection control interventions and Clostridioides difficile infections: Analysis of six-year time-series data in a tertiary-care hospital in Greece.

To investigate the association between Clostridioides difficile infection (CDI), antibiotic use, and infection control interventions, during an antibiotic stewardship program (ASP) implemented in a tertiary-care hospital in Greece from 2013 to 2018. Analysis was applied for the following monthly indices: 1. consumption of antibiotics; 2. use of hand hygiene disinfectant solutions; 3. percentage of isolations of patients either with multidrug-resistant (MDR) bacteria, or CDI, or admitted from another hospital; and 4. percentage of patients with CDI divided into two groups: community-acquired CDI (CACDI) and hospital-associated CDI (HACDI) (onset ≤72h and >72h after admission, respectively). During the study, a significant reduction in CACDI rate from 0.3%/admissions [95% CI 0.1-0.6] to 0.1%/admissions [95% CI 0.0-0.3] (p-value=0.035) was observed in adults ICU, while CDI rates were stable in the rest of the hospital. Antibiotic consumption showed a significant reduction in total hospital, from 91.7 DDDs [95% CI 89.7-93.7] to 80.1 DDDs [95% CI 79.1-81.1] (p-value<0.001), except adults ICU. Non-advanced antibiotics correlated with decreased CDI rates in Adults Clinic Departments and ICU. Isolation of patients one and two months earlier correlated with decreased CACDI rates per 20% [95% CI 0.64-1.00, p-value=0.046] and HACDI per 23% [95% CI 0.60-1.00, p-value=0.050] in Adults Clinic Departments. Consumption of disinfectant solutions current month correlated with decreased rate for CACDI per 33% [95% CI 0.49-0.91, p-value=0.011] and HACDI per 38% [95% CI 0.40-0.98, p-value=0.040] in total Hospital Clinics. Rational antibiotic prescribing during ASP along with multipronged intervention strategy focusing on hand hygiene and patient isolation measures prevent and control CDI outbreaks in the hospital setting.

Economic Viability of Penicillin Allergy Testing to Avoid Improper Clindamycin Surgical Prophylaxis.

Patients mislabeled with a penicillin allergy are often unnecessarily given prophylactic clindamycin. Thus, otolaryngologists may cause harm due to clindamycin's associated risk of Clostridioides difficile infections (CDI) and surgical site infections (SSI). The objective of this study was to determine the economic feasibility of penicillin allergy testing in preventing unnecessary clindamycin use among patients with an unconfirmed penicillin allergy prior to otolaryngologic surgery. A break-even analysis was performed using the average cost of penicillin allergy testing and a CDI/SSI to calculate the absolute risk reduction (ARR) in baseline CDI/SSI rate due to clindamycin required for penicillin testing to be economically sustainable. The binomial distribution was used to calculate the probability that current penicillin testing can achieve this study's ARR. Preoperative penicillin testing was found to be economically sustainable if it could decrease the baseline CDI rate by an ARR of 1.06% or decrease the baseline SSI rate by an ARR of 1.34%. The probability of penicillin testing achieving these ARRs depended on the baseline CDI and SSI rates. When the CDI rate was at least 5% or the SSI rate was at least 7%, penicillin allergy testing was guaranteed to achieve economic sustainability. In patients mislabeled with a penicillin allergy, preoperative penicillin allergy testing may be an economically sustainable option to prevent the unnecessary use of prophylactic clindamycin during otolaryngologic surgery. Current practice guidelines should be modified to recommend penicillin allergy testing in patients with an unconfirmed allergy prior to surgery. NA Laryngoscope, 133:1086-1091, 2023.

Reappraisal of the clinical role of metronidazole therapy for Clostridioides difficile infection in Taiwan: A multicenter prospective study

Although metronidazole is not recommended to treat Clostridioides difficile infection (CDI) in Western countries, it was still to be recommended for the treatment of non-severe CDI among Taiwanese adults in 2020. This controversy in the clinical role of metronidazole therapy for CDI was examined in a prospective clinical study. The study was conducted from January 2015 to December 2016 in three hospitals in Taiwan. Metronidazole treatment failure (MTF) was defined as the persistence of diarrhea after six days of treatment, medication modification (shifting to oral vancomycin), or death after five days of therapy. Overall, 325 patients receiving metronidazole for CDI were included. The overall MTF rate was 48.6% (158 patients). Leukocyte counts of >15,000cells/mL in peripheral blood (odd ratio [OR] 1.81; P=0.04) and congestive heart failure (OR 3.26; P=0.02) were independently associated with MTF. The MTF rate for patients with leukocyte counts of ≤15,000cells/mL and no congestive heart failure, leukocyte counts of >15,000cells/mL and no congestive heart failure, leukocyte counts of ≤15,000cells/mL and congestive heart failure, and leukocyte counts of >15,000cells/mL and congestive heart failure were 44.2%, 51.8%, 73.3%, and 66.7%, respectively. Of note, patients who experienced MTF had a higher recurrence rate of CDI than those with metronidazole treatment success (13.9% vs. 6.0%, P=0.02). For Taiwanese adults with CDI, the failure rate of metronidazole therapy approached 50%, which suggests the reappraisal of the therapeutic role of metronidazole therapy, especially for patients with leukocytosis or underlying congestive heart failure.

Systematic Review and Meta-Analysis: Safety and Efficacy of Saccharomyces boulardii for Prevention of Clostridioides difficile Infection

Background Clostridioides difficile infection (CDI) is associated with frequent recurrences. The role of probiotics in preventing CDI remains unclear despite patients frequently using them. Methods We performed a systematic-review and meta-analysis to evaluate the role of Saccharomyces boulardii, a yeast probiotic, in preventing primary or recurrent CDI in patients on systemic antimicrobial therapy. We searched MEDLINE, Embase, and Web of Science up to December 2021 to identify studies (case-control, cohort, or clinical trial studies) reporting the use of systemic antimicrobials with or without S. boulardii and providing information on primary or recurrent CDI. Pooled odds ratios with 95% confidence intervals were calculated using a random effects model. Results Eight studies (six randomized control trials and two cohort studies) were included. Six studies with 9,712 patients evaluated primary prevention. The rate of CDI in patients who received S. boulardii was 0.73% (44/5977) compared to 1.09% (41/3735) in the control group. Meta-analysis showed no difference in the risk of CDI among the two groups (odds ratio [OR], 0.71; 95%CI, 0.46–1.10; p = 0.124) with no significant heterogeneity (I2 = 0%). In two studies with 292 patients evaluating secondary prevention, the rate of recurrent CDI was 36.73% (54/147) on S. boulardii compared to 46.20% (67/145) in controls, with no significant difference (p = 0.19). Subgroup analysis of studies using S. boulardii (250 mg twice daily) showed no difference in the CDI risk with or without S. boulardii. No serious adverse events from S. boulardii were noted. Conclusion The use of S. boulardii appears to have no benefit for preventing either primary or recurrent CDI in patients taking systemic antimicrobials.

Hospitalization With Clostridioides difficile in Pediatric Inflammatory Bowel Disease: a Population-Based Study.

Objectives:Several studies have demonstrated higher rates of Clostridioides difficile infection (CDI) in adults with inflammatory bowel disease (IBD). We conducted a population-based study comparing the risk of hospitalization with CDI in children with and without IBD.Methods:Using health administrative data and validated algorithms, we identified all children (<16 years) diagnosed with IBD in 5 Canadian provinces, then age and sex matched to 5 children without IBD. Province-specific 5-year incidence rates of hospitalization with CDI were pooled and generalized linear mixed-effects models were used to estimate the crude incidence rate ratio (IRR) comparing (1) children with and without IBD and (2) children with Crohn disease and ulcerative colitis. Hazard ratios (HR) from Cox proportional hazards models adjusting for age, sex, rural/urban household, and income were pooled using fixed-effects models.Results:The incidence rate of CDI identified during hospitalization was 49.06 [95% confidence interval (CI), 39.40–61.08] per 10,000 person-years (PY) in 3593 children with IBD compared to 0.39 (95% CI, 0.13–1.21) per 10,000 PY in 16,284 children without IBD (crude IRR, 133.4, 95% CI, 42.1–422.7; adjusted HR, 68.2, 95% CI, 24.4–190.4). CDI was identified less often in children with Crohn disease than ulcerative colitis (crude IRR, 0.51, 95% CI, 0.32–0.82; adjusted HR, 0.69, 95% CI, 0.46–1.05).Conclusions:Children with IBD have a markedly higher incidence of CDI identified during a hospitalization relative to children without IBD. Consequently, symptomatic children with IBD who are hospitalized should be screened for CDI.

Characterization of Healthcare-Associated and Community-Associated Clostridioides difficile Infections among Adults, Canada, 2015-2019.

We investigated epidemiologic and molecular characteristics of healthcare-associated (HA) and community-associated (CA) Clostridioides difficile infection (CDI) among adult patients in Canadian Nosocomial Infection Surveillance Program hospitals during 2015–2019. The study encompassed 18,455 CDI cases, 13,735 (74.4%) HA and 4,720 (25.6%) CA. During 2015–2019, HA CDI rates decreased by 23.8%, whereas CA decreased by 18.8%. HA CDI was significantly associated with increased 30-day all-cause mortality as compared with CA CDI (p<0.01). Of 2,506 isolates analyzed, the most common ribotypes (RTs) were RT027, RT106, RT014, and RT020. RT027 was more often associated with CDI-attributable death than was non-RT027, regardless of acquisition type. Overall resistance C. difficile rates were similar for all drugs tested except moxifloxacin. Adult HA and CA CDI rates have declined, coinciding with changes in prevalence of RT027 and RT106. Infection prevention and control and continued national surveillance are integral to clarifying CDI epidemiology, investigation, and control.

Trends in facility-level rates of Clostridioides difficile infections in US hospitals, 2019-2020.

The coronavirus disease 2019 pandemic caused substantial changes to healthcare delivery and antibiotic prescribing beginning in March 2020. To assess pandemic impact on Clostridioides difficile infection (CDI) rates, we described patients and trends in facility-level incidence, testing rates, and percent positivity during 2019-2020 in a large cohort of US hospitals. We estimated and compared rates of community-onset CDI (CO-CDI) per 10,000 discharges, hospital-onset CDI (HO-CDI) per 10,000 patient days, and C. difficile testing rates per 10,000 discharges in 2019 and 2020. We calculated percent positivity as the number of inpatients diagnosed with CDI over the total number of discharges with a test for C. difficile. We used an interrupted time series (ITS) design with negative binomial and logistic regression models to describe level and trend changes in rates and percent positivity before and after March 2020. In pairwise comparisons, overall CO-CDI rates decreased from 20.0 to 15.8 between 2019 and 2020 (P < .0001). HO-CDI rates did not change. Using ITS, we detected decreasing monthly trends in CO-CDI (-1% per month, P = .0036) and HO-CDI incidence (-1% per month, P < .0001) during the baseline period, prior to the COVID-19 pandemic declaration. We detected no change in monthly trends for CO-CDI or HO-CDI incidence or percent positivity after March 2020 compared with the baseline period. While there was a slight downward trajectory in CDI trends prior to March 2020, no significant change in CDI trends occurred during the COVID-19 pandemic despite changes in infection control practices, antibiotic use, and healthcare delivery.

Development of an Effective Nontoxigenic Clostridioides difficile-Based Oral Vaccine against C. difficile Infection.

ABSTRACTThe symptoms of Clostridioides difficile infection (CDI) are largely attributed to two C. difficile toxins, TcdA and TcdB. Significant efforts have been devoted to developing vaccines targeting both toxins through parenteral immunization routes. Recently, we generated a novel chimeric protein (designated Tcd169), comprised of the glucosyltransferase domain (GT), the cysteine protease domain (CPD), and the receptor binding domain (RBD) of TcdB, and the RBD of TcdA. Parenteral immunizations with Tcd169 provide mice effective protection against infection with a ribotype (RT) 027 C. difficile strain. In this study, we expressed Tcd169 in a nontoxigenic C. difficile CCUG37785 strain (designated NTCD), resulting in strain NTCD_Tcd169 to develop an oral vaccine that can target both C. difficile toxins and colonization/adhesion factors. Oral immunizations with NTCD_Tcd169 spores induced systematic and mucosal antibody responses against, not only both toxins, but also C. difficile flagellins (FliC/FliD). Intriguingly yet importantly, anti-Tcd169 sera raised against Tcd169 protein were significantly cross-reactive with FliC/FliD and two surface layer proteins (SlpA and Cwp2). Oral immunizations with NTCD_Tcd169 spores provided mice effective protection against infection with a hypervirulent RT027 C. difficile strain R20291and significantly reduced R20291spore numbers in feces compared with NTCD or PBS immunized mice. These results imply that the genetically modified, nontoxigenic C. difficile strain expressing Tcd169 may represent a novel mucosal vaccine candidate against CDI.IMPORTANCE Clostridioides difficile is an enteric pathogen, and symptoms of C. difficile infection (CDI) are mainly by two exotoxins TcdA and TcdB. Active vaccination is cost-effective approach to prevent CDI and high rates of recurrence. Ideally, vaccines should target both C. difficile toxins and cell/spore colonization. In this study, we expressed immunodominant fragments of TcdA and TcdB (i.e., Tcd169) in a nontoxigenic C. difficile CCUG37785 strain, generating a promising oral/mucosal vaccine candidate against CDI, by targeting both toxins and colonization of pathogenic C. difficile strains. Importantly, anti-Tcd169 sera raised against Tcd169 protein were significantly cross-reactive with FliC/FliD and two surface layer proteins (SlpA and Cwp2), and all of which are involved in C. difficile adhesion/colonization in vitro and in vivo.