Development Of Clostridioides Difficile Infection Research Articles

Epidemiologic characteristics and risk factors of Clostridioides difficile infection in patients with active tuberculosis in the Republic of Korea: a nationwide population-based study

The relationship between anti-tuberculosis (TB) agents and Clostridioides difficile infection (CDI) remains unclear. This study aimed to investigate the epidemiological characteristics and risk factors for CDI in patients with TB. This nationwide, population-based cohort study was conducted in the Republic of Korea (ROK) between January 2018 and December 2022. Data were extracted from the National Health Insurance Service-National Health Information Database. The risk factors for CDI in patients with TB were identified through multi-variate logistic regression analysis using a 1:4 greedy matching method based on age and sex. During the study period, CDI developed in 2901 of the 131,950 patients with TB who were prescribed anti-TB agents. The incidence of CDI in patients with TB has increased annually in the ROK from 12.31/1000 in 2018 to 33.51/1000 in 2022. Oral metronidazole (81.94%) was the most common first-line treatment for CDI. The in-hospital mortality rate of patients with concomitant CDI and TB was 9.9%, compared with 6.9% in those with TB alone (P<0.0001). Multi-variate logistic regression analysis found intensive care unit admission, Charlson Comorbidity Index ≥3, antibiotic exposure, standard regimen, multi-drug-resistant TB and extrapulmonary TB to be significant risk factors for development of CDI in patients with TB. CDI is uncommon in patients with TB, but it results in a significantly increased mortality rate. Patients being treated for TB should be monitored carefully for the development of CDI. Further clinical research is warranted to identify effective interventions for preventing and controlling CDI during TB treatment.

Prediction of 28-Day All-Cause Mortality in Heart Failure Patients with Clostridioides difficile Infection Using Machine Learning Models: Evidence from the MIMIC-IV Database.

Heart failure (HF) may induce bowel hypoperfusion, leading to hypoxia of the villa of the bowel wall and the occurrence of Clostridioides difficile infection (CDI). However, the risk factors for the development of CDI in HF patients have yet to be fully illustrated, especially because of a lack of evidence from real-world data. Clinical data and survival situations of HF patients with CDI admitted to ICU were extracted from the Medical Information Mart for Intensive Care (MIMIC)-IV database. For developing a model that can predict 28-day all-cause mortality in HF patients with CDI, the Recursive Feature Elimination with Cross-Validation (RFE-CV) method was used for feature selection. And nine machine learning (ML) algorithms, including logistic regression (LR), decision tree, Bayesian, adaptive boosting, random forest (RF), gradient boosting decision tree, XGBoost, light gradient boosting machine, and categorical boosting, were applied for model construction. After training and hyperparameter optimization of the models through grid search 5-fold cross-validation, the performance of models was evaluated by the area under curve (AUC), accuracy, sensitivity, specificity, precision, negative predictive value, and F1 score. Furthermore, the SHapley Additive exPlanations (SHAP) method was used to interpret the optimal model. A total of 526 HF patients with CDI were included in the study, of whom 99 cases (18.8%) experienced death within 28 days. Eighteen of the 57 variables were selected for the model construction algorithm for model construction. Among the ML models considered, the RF model emerged as the optimal model achieving the accuracy, F1-score, and AUC values of 0.821, 0.596, and 0.864, respectively. The net benefit of the model surpassed other models at 16%-22% threshold probabilities based on decision curve analysis. According to the importance of features in the RF model, red blood cell distribution width, blood urea nitrogen, Simplified Acute Physiology Score II, Sequential Organ Failure Assessment, and white blood cell count were highlighted as the five most influential variables. We developed ML models to predict 28-day all-cause mortality in HF patients associated with CDI in the ICU, which are more effective than the conventional LR model. The RF model has the best performance among all the ML models employed. It may be useful to help clinicians identify high-risk HF patients with CDI.

Antibiotic use and risk of Clostridioides difficile infection in patients with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) have an increased risk of Clostridioides difficile infection (CDI) compared with those without IBD, which is worsened with antibiotic usage. While prior studies have shown a correlation between CDI development and certain classes of antibiotics, the IBD population has not been well represented. This study evaluates the rates of CDI with outpatient antibiotic use in patients with IBD. We conducted a retrospective cohort study composed of patients with IBD and compared the incidence of CDI in patients who received an outpatient prescription for antibiotics (6694 patients) against those without prescriptions (6025 patients) from 2014 to 2020 at our institution. We compared CDI rates based on nine antibiotic classes: penicillins, cephalosporins, sulfonamides, tetracyclines, macrolides, quinolones, clindamycin, metronidazole, and nitrofurantoin. The risk of CDI was low (0.7%) but significantly higher for those with antibiotic exposure (0.9% vs 0.5%, P=0.005) and had a positive correlation with a smoking history. The increased risk of CDI in the IBD population was attributable to the clindamycin and metronidazole classes (odds ratio=4.7, 95% confidence interval: 1.9-11.9, P=0.001; odds ratio=3.6, 95% confidence interval: 2.1-6.2, P<0.0001, respectively). The use of clindamycin or metronidazole prescribed in an outpatient setting was associated with a statistically significant increased risk of CDI in patients with IBD. Although the association between clindamycin and CDI is a well-established and common finding, the association between metronidazole and CDI is unique in this study.

Characterization and dynamics of intestinal microbiota in patients with Clostridioides difficile colonization and infection

Gut microbiota dysbiosis increases the susceptibility to Clostridioides difficile infection (CDI). In this study, we monitored C. difficile colonization (CDC) patients from no CDC status (CDN) to CDC status (CDCp) and CDI patients from asymptomatic status before CDI (PRECDI), CDI status (ONCDI), to asymptomatic status after CDI (POSTCDI). Based on metagenomic sequencing, we aimed to investigate the interaction pattern between gut microbiota and C. difficile. There was no significant difference of microbiota diversity between CDN and CDCp. In CDCp, Bacteroidetes and short-chain fatty acid (SCFA)-producing bacteria increased, with a positive correlation between SCFA-producing bacteria and C. difficile colonization. Compared with PRECDI, ONCDI and POSTCDI showed a significant decrease in microbiota diversity, particularly in Bacteroidetes and SCFA-producing bacteria, with a positive correlation between opportunistic pathogen and C. difficile. Fatty acid metabolism, and amino acid biosynthesis were enriched in CDN, CDCp, and PRECDI, while bile secretion was enriched in ONCDI and POSTCDI. Microbiota and metabolic pathways interaction networks in CDN and CDCp were more complex, particularly pathways in fatty acid and bile acid metabolism. Increasing of Bacteroidetes and SCFA-producing bacteria, affecting amino acid and fatty acid metabolism, is associated with colonization resistance to C. difficile and inhibiting the development of CDI.

P1149 Risk of Clostridioides difficile infection in patients with inflammatory bowel disease

Abstract Background Patients with inflammatory bowel disease (IBD) are at increased risk of Clostridioides difficile infection (CDI). CDI in IBD patients has been associated with poor clinical outcomes including higher morbidity and mortality. Immunosuppressant therapy has been proposed as a risk factor for CDI. However, the particular relationship between biologic therapy and CDI is controversial. We aimed to assess whether biologic therapy increased the risk of developing CDI in three cohorts of patients with immune-mediated inflammatory diseases (IBD and rheumatic diseases). Methods We conducted a retrospective study including three cohorts: IBD patients receiving biologic therapies (IBD-Bio), IBD patients treated with non-biologic therapies (IBD-Bio-naïve), and patients with rheumatic diseases receiving biologics (RHEUMA-Bio). Different biologic agents were considered for IBD-Bio cohort: infliximab, adalimumab, golimumab, certolizumab, ustekinumab, and vedolizumab. For RHEUMA-Bio, the biologics included were infliximab, adalimumab, golimumab, certolizumab, ustekinumab, secukinumab, etanercept, abatacept, tocilizumab, rituximab, guselkumab and ixekizumab. We estimated the incidence rate (IR) of CDI episodes between 2015 and 2021 among the three cohorts. Risk factors of CDI were assessed using logistic regression model. Furthermore, we performed subgroup analysis to identify risk factors of CDI in the IBD cohorts (IBD-Bio and IBD-Bio-naïve) and within the IBD-Bio cohort. We used R software for data analysis. Results Overall, we included 1868 patients, 603 in IBD-Bio, 440 in IBD-Bio-naïve, and 825 in the RHEUMA-Bio cohort. The number of CDI episodes was 3, 42, and 25 for the RHEUMA-Bio, IBD-Bio, and IBD-Bio-naïve cohorts, respectively. The IR for CDI was 1.27 100 person-years (95% confidence interval [95% CI], 0.91-1.71) for IBD-Bio, followed by 0.95 100 person-years (95% CI 0.61-1.40) for IBD-Bio-naïve and declined to 0.07 100 person-years (95% CI 0.01-0.20) for RHEUMA-Bio cohort. We identified having IBD (odds ratio [OR]:18.98, CI 95% 5.82- 61.92, p&amp;lt;0.001) as the major risk factor for developing CDI after adjusting for age, sex, need for biologics, and comorbidities in the three cohorts. Among IBD patients, there were no differences in CDI between biologic and naive cohorts. Within the IBD-Bio cohort, the number of biologics received (OR: 1.56, CI 95% 1.22- 2.01, P&amp;lt;0.001) and short disease duration (1.08, CI 95% 1.04- 1.13, P&amp;lt;0.001) were associated with a higher risk of CDI. Conclusion The major risk factor associated with CDI development was the diagnosis of IBD. Biologic therapy was not associated with a higher risk of CDI. In IBD patients on biologic therapy, the number of biologics received increased the risk of CDI.

Prevention and treatment of C. difficile in cancer patients.

We provide an update on the recent literature on Clostridioides difficile infection (CDI) in cancer patients. Distinguishing between colonization and infection remains challenging in cancer patients. Many patients with negative toxin analysis are still treated for CDI, and some meet criteria for severe cases. The incidence of CDI is high in cancer patients, especially those with haematological malignancies. Disruption of the gut microbiome due to antibiotic consumption, chemotherapy and radiotherapy is the primary factor contributing to CDI development. The severity of CDI in cancer patients is often unclear due to the absence of well-defined severity criteria. Certain microbiome species predominance and specific ribotypes have been associated with worse outcomes. Whole genome sequencing could be helpful for differentiating recurrence from reinfection and exploring potential nosocomial transmission. While certain new drugs such as fidaxomicin or bezlotoxumab show promise, the optimal treatment and prevention strategies for CDI in cancer patients remain uncertain. Faecal microbiota transplantation (FMT) holds potential for reducing CDI recurrence rates. Further studies are needed to provide robust recommendations for diagnosis, grading severity, and therapeutic management of CDI in cancer patients. Recurrences are particularly concerning due to subsequent exposition to CDI risk factors.

High Prevalence of Clostridioides difficile Ribotype 176 in the University Hospital in Kosice.

Dysbiosis of the gut microbiota, caused by antibiotics, plays a key role in the establishment of Clostridioides difficile CD). Toxin-producing strains are involved in the pathogenesis of Clostridioides difficile infection (CDI), one of the most common hospital-acquired infections. We cultured a total of 84 C. difficile isolates from stool samples of patients hospitalized at Louis Pasteur University Hospital in Kosice, Slovakia, that were suspected of CDI and further characterized by molecular methods. The presence of genes encoding toxin A, toxin B, and binary toxin was assessed by toxin-specific PCR. CD ribotypes were detected using capillary-based electrophoresis ribotyping. A total of 96.4% of CD isolates carried genes encoding toxins A and B, and 54.8% of them were positive for the binary toxin. PCR ribotyping showed the presence of three major ribotypes: RT 176 (n = 40, 47.6%); RT 001 (n = 23, 27.4%); and RT 014 (n = 7, 8.3%). Ribotype 176 predominated among clinical CD isolates in our hospital. The proportion of RT 176 and RT 001 in four hospital departments with the highest incidence of CDI cases was very specific, pointing to local CDI outbreaks. Based on our data, previous use of antibiotics represents a significant risk factor for the development of CDI in patients over 65 years of age.

Screening for Clostridioides difficile colonization at admission to the hospital: a multi-centre study

ObjectivesTo assess the value of screening for Clostridioides difficile colonization (CDC) at hospital admission in an endemic setting. MethodsA multi-centre study was conducted at four hospitals located across the Netherlands. Newly admitted patients were screened for CDC. The risk of development of Clostridioides difficile infection (CDI) during admission and 1-year follow-up was assessed in patients with and without colonization. C. difficile isolates from patients with colonization were compared with isolates from incident CDI cases using core genome multi-locus sequence typing to determine whether onwards transmission had occurred. ResultsCDC was present in 108 of 2211 admissions (4.9%), whereas colonization with a toxigenic strain (toxigenic Clostridoides difficile colonization [tCDC]) was present in 68 of 2211 admissions (3.1%). Among these 108 patients with colonization, diverse PCR ribotypes were found and no ‘hypervirulent’ PCR ribotype 027 (RT027) was detected (95% CI, 0–0.028). None of the patients with colonization developed CDI during admission (0/49; 95% CI, 0–0.073) or 1-year follow-up (0/38; 95% CI, 0–0.93). Core genome multi-locus sequence typing identified six clusters with genetically related isolates from patients with tCDC and CDI; however, in these clusters, only one possible transmission event from a patient with tCDC to a patient with CDI was identified based on epidemiological data. ConclusionIn this endemic setting with a low prevalence of ‘hypervirulent’ strains, screening for CDC at admission did not detect any patients with CDC who progressed to symptomatic CDI and detected only one possible transmission event from a patient with colonization to a patient with CDI. Thus, screening for CDC at admission is not useful in this setting.

Clostridioides difficile Infection in Patients with Cirrhosis Treated for Hepatic Encephalopathy

Introduction Hospitalizations, proton-pump inhibitors (PPI), and systemic antibiotics increase the risk of Clostridioides difficile infection (CDI) in cirrhosis. We compare the risk of CDI with hepatic encephalopathy (HE) medications, hypothesizing that rifaximin may decrease CDI risk. Materials and Methods A retrospective study of hospitalized HE patients treated with lactulose and/or rifaximin at Mayo Clinic Minnesota, Florida, and Arizona from 2008 to 2013 was conducted. Data on demographics, hospitalizations, antibiotics, and PPI use and CDI were gathered. Univariate and multivariable cox models were constructed. Results We found 1,112 hospitalizations in 1,055 unique patients (55 had 1 subsequent readmission, 1 patient had 2); 428 (40.6%) patients were women (median age: 58 years [interquartile range: 52–65]). CDI developed after 66/1,112 (5.9%) hospitalizations within 12 months post-discharge. Lactulose was administered in 21 (31.8%), rifaximin in 5 (7.6%), both in 40 (60.6%) hospitalizations. Systemic antibiotics were used in 28 (42.4%) patients and PPIs in 60 (90.9%) patients.Univariate analysis using medication (with lactulose alone as the reference group) showed rifaximin was not significantly associated with CDI compared with lactulose (hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 0.57–4.33, p = 0.39). Use of both medications was not significant compared with lactulose (HR: 1.41, 95% CI: 0.84–2.38, p = 0.19). Results were similar after controlling for confounders. Multivariable analysis based on length of stay, age, and gender showed no differences between rifaximin versus lactulose and both versus lactulose. Conclusion There is no significant difference between lactulose and rifaximin on CDI development in HE patients. However, CDI should still be considered when managing diarrhea in HE patients.

Incidence, predictors, and 30-day outcomes of Clostridioides difficile infection in patients undergoing cystectomy: A national database analysis

Clostridioides difficile infection (CDI) is the second most common health care acquired infection (HAI) and the most common gastrointestinal HAI, with an estimated 365,200 cases reported by the center for disease control in 2017. CDI continues to remain a major cause of inpatient admission and utilization of health care resources. This study aimed to determine the true incidence, risk factors, and outcomes of CDI in patients undergoing cystectomy. We conducted an analysis of patients undergoing cystectomy between 2015 and 2017 using the American college of surgeon National Surgical Quality Improvement Program to study the incidence, risk factors, and 30 day postsurgical outcomes associated with CDI following cystectomy. Developed by the American College of Surgery, this is a nationally validated, risk adjusted, and outcomes based program designed to determine and improve the quality of surgical and postsurgical care. The incidence of CDI following cystectomy was 3.6% in our patient cohort. About 18.8% of patients developed CDI following hospital discharge. None elective surgeries and complete cystectomy procedures had a higher rate of CDI. About 48.4% of patients with CDI had a preceding postoperative infection. Postoperative organ space infections, postoperative renal failure, postoperative sepsis, and septic shock were independently associated with the development of CDI, (all P < 0.05). Patients who developed postoperative CDI during hospitalization had lengthier hospital admissions than those who did not develop a CDI and had a higher risk of deep venous thrombosis formation. A sizable number of patients experience CDIs after cystectomy procedures in the USA, and CDI development is associated with an increase in length of stay and unplanned readmissions. Interventions and initiatives are needed to reduce this burden of disease.

897. Criteria Restricting Inappropriate Meropenem Empiricism (CRIME): A Quasi-Experimental Carbapenem Restriction Pilot at a Large Academic Medical Center

Abstract Background Carbapenems’ broad spectrum of activity may make these agents appealing for empiric use; however, their use is associated with development of Clostridioides difficile infection (CDI) and multi-drug resistance. Selective use of carbapenems is vital in maintaining their effectiveness. Our study aimed to examine the impact of meropenem restriction criteria on utilization and patient outcomes. Methods This single-center, quasi-experimental study was conducted at an academic medical center where an initial medication use analysis found frequent inappropriate meropenem utilization. The antimicrobial stewardship team developed restriction criteria and implemented a pilot in February 2022. Investigators aimed to determine how restriction criteria affected meropenem utilization across 8 weeks in the pre-implementation period compared to the post-implementation period. The primary outcome was to compare the inappropriateness of meropenem utilization. Secondary outcomes included comparison of days of therapy per 1000 patient-days (DOT/1000 PD), hospital length of stay (LOS), frequency of CDI, and acquisition cost. Results Across the 8 week timeframes, reductions in inappropriate meropenem use (64.5% vs 12.8%; p&amp;lt; 0.001), duration of therapy (5.8 [3.2-7.3] vs. 2.4 [1.0-5.5] days, p&amp;lt; 0.0001), and utilization (30.5 vs. 8.3 DOT/1000 PD, p=0.04) in the pre- and post-implementation periods, respectively, were observed. Total number of meropenem orders decreased by 65% (p&amp;lt; 0.001). Implementation of restriction criteria also resulted in decreased median hospital LOS between periods (11.9 [7.8-20.4] vs. 9.2 [5.4-15.2] days, p=0.05). There was no difference in frequency of CDI (2 vs. 0, p=0.99). Projected annual cost savings was approximately $57,300. Conclusion Implementation of antimicrobial stewardship-initiated restriction criteria can reduce inappropriate utilization of meropenem, overall number of orders, and total duration of therapy. Disclosures Kerry O. Cleveland, MD, AbbVie: Honoraria|Cumberland: Honoraria|Merck: Honoraria|Pfizer: Honoraria.

391. Evaluation of oral vancomycin treatment for hospital-acquired Clostridioides difficile infection prophylaxis in a community hospital: A retrospective cohort study

Abstract Background Hospital-acquired (HA) Clostridioides difficile infection (CDI) is among the most common hospital-acquired infections and is a leading cause of morbidity and mortality among hospitalized older adults. Oral vancomycin prophylaxis (OVP) has been demonstrated in recent studies to reduce the incidence of HA CDI. This study aims to evaluate the effectiveness of OVP in the prevention of HA CDI in a community hospital setting. Methods We developed a protocol to administer prophylactic oral vancomycin based on patients’ risk factors and implemented it at our community hospital in Evanston, Illinois, in September 2020. The intervention group consists of patients admitted to our hospital between October 1, 2020, to March 31, 2021, who received OVP. Patients admitted between October 1, 2019, to March 31, 2020, who had at least one risk factor of CDI and met the inclusion criteria of OVP protocol were selected as the control group. Electronic medical records were retrospectively collected and analyzed. Propensity score matching was performed for a one-to-one match between two groups. Logistic regression models were used to study the relationship between HA CDI and independent variables, including OVP, risk factors of CDI, and demographic characteristics. Table 1.Sample characteristics of the control and intervention groups A Student t-test was performed for continuous parameters. A Chi-square test was performed for categorical parameters. Non PPx = control group; OVP PPx = oral vancomycin prophylaxis group; SNF = skilled nursing facility; LOS = length of stay; PPI = proton pump inhibitor; H2RA = histamine 2 receptor antagonist. Results A total of 446 patients (267 in the intervention group and 179 in the control group) were included. The sample characteristics are summarized in Table 1. 4/175 (2.2%) patients in the control group developed HA CDI, compared with 12/255 (4.5%) in the intervention group. Before matching, patients who received OVP (OR=7.62, p=0.010) and had a longer length of stay (LOS, OR=1.11, p=0.002) were found to have increased odds ratios (OR) of development of HA CDI (Table 2). After propensity score matching, 4/176 (2.3%) patients in the control group developed HA CDI, compared with 5/176 (2.8%) (Figure 1). Patients from skilled nursing facilities (SNF, OR=15.41, p=0.021) and with longer LOS (OR 1.15, p=0.005) were found to be associated with higher OR of HA CDI (Table 3). Table 2.The odds ratio of development of hospital-acquired C.diff infection among control and intervention groups. A binary logistic regression model was used for this study. CI = 95% confidence interval. R2 Tujur = coefficients of determination (D); AIC = Akaike’s Information Criteria. OVP PPx = oral vancomycin prophylaxis group; SNF = skilled nursing facility; LOS = length of stay; PPI = proton pump inhibitor; H2RA = histamine 2 receptor antagonist. Figure 1.Propensity score matching of control and intervention groups. (A) Distribution of propensity scores between unmatched and matched control and intervention groups. (B) Distribution balance of propensity score before and after matching. Treatment o = control group; Treatment 1 = OVP intervention group. (C) The distribution balance of covariates used for propensity score calculation before and after matching. (D) Summary of propensity score matching results. HA CDI = hospital-acquired C.diff infection (after propensity score matching). Table 3.The odds ratio of development of hospital-acquired C.diff infection among control and intervention groups after propensity score matching. A binary logistic regression model was used for this study. CI = 95% confidence interval. R2 Tujur = coefficients of determination (D); AIC = Akaike’s Information Criteria. OVP PPx = oral vancomycin prophylaxis group; SNF = skilled nursing facility; LOS = length of stay; PPI = proton pump inhibitor; H2RA = histamine 2 receptor antagonist. Conclusion Prophylactic administration of oral vancomycin to patients with selected risk factors has no statistical significance in reducing or preventing HA CDI. A longer length of hospital stay may be associated with higher risk for developing HA CDI. Disclosures All Authors: No reported disclosures.

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.

Epigallocatechin-3-Gallate Improves Intestinal Gut Microbiota Homeostasis and Ameliorates Clostridioides difficile Infection.

Clostridioides difficile infection is closely related to the intestinal flora disorders induced by antibiotics, and changes in the intestinal flora may cause the occurrence and development of Clostridioides difficile infection. Epigallocatechin-3-gallate (EGCG) is one of the major bioactive ingredients of green tea and has been suggested to alleviate the growth of C. difficile in vitro. EGCG can ameliorate several diseases, such as obesity, by regulating the gut microbiota. However, whether EGCG can attenuate C. difficile infection by improving the gut microbiota is unknown. After establishing a mouse model of C. difficile infection, mice were administered EGCG (25 or 50 mg/kg/day) or PBS intragastrically for 2 weeks to assess the benefits of EGCG. Colonic pathology, inflammation, the intestinal barrier, gut microbiota composition, metabolomics, and the transcriptome were evaluated in the different groups. Compared with those of the mice in the CDI group, EGCG improved survival rates after infection, improved inflammatory markers, and restored the damage to the intestinal barrier. Furthermore, EGCG could improve the intestinal microbial community caused by C. difficile infection, such as by reducing the relative abundance of Enterococcaceae and Enterobacteriaceae. Moreover, EGCG can increase short-chain fatty acids, improve amino acid metabolism, and downregulate pathways related to intestinal inflammation. EGCG alters the microbiota and alleviates C. difficile infection, which provides new insights into potential therapies.

Criteria Restricting Inappropriate Meropenem Empiricism (CRIME): a quasi-experimental carbapenem restriction pilot at a large academic medical centre

The broad-spectrum activity of carbapenems makes them appealing for empirical use; however, they are associated with development of Clostridioides difficile infection (CDI) and multidrug resistance. Selective carbapenem use is vital in maintaining their effectiveness. We examined the impact of meropenem restriction criteria on utilisation and patient outcomes. This quasi-experimental study was conducted at a single academic medical centre after medication use evaluation found frequent inappropriate meropenem utilisation. Antimicrobial stewardship-led restriction criteria were developed and implemented in February 2022. Investigators aimed to determine how restriction criteria affected meropenem utilisation across 8 weeks in the pre- (February-April 2020) versus post-implementation period (February-April 2022). The primary outcome was inappropriateness of meropenem utilisation. Secondary outcomes included days of therapy per 1000 patient-days (DOT/1000 PD), hospital length of stay (LOS), CDI Standardized Infection Ratio (SIR), and acquisition cost. Across the 8-week timeframes, reductions in inappropriate meropenem use (64.5% vs. 12.8%; P < 0.001), duration of therapy [5.8 (3.2-7.3) vs. 2.4 (1.0-5.5) days; P < 0.001] and utilisation (30.5 vs. 8.3 DOT/1000 PD; P < 0.001) pre- versus post-implementation were observed. Total meropenem orders decreased by 65% (P < 0.001). Median hospital LOS also decreased between periods [11.9 (7.8-20.4) vs. 9.2 (5.4-15.2) days], although not statistically significant (P=0.051). There was no difference in CDI SIR (0.1 vs. 0.1; P=0.99). Projected annual cost savings were ∼US$57 300. Implementation of antimicrobial stewardship-initiated restriction criteria can reduce inappropriate meropenem utilisation, overall number of orders, and total duration of therapy.

Risk Factors, Diagnosis, and Management of Clostridioides difficile Infection in Patients with Inflammatory Bowel Disease

Clostridioides difficile infection (CDI) and inflammatory bowel disease (IBD) are two pathologies that share a bidirectional causal nexus, as CDI is known to have an aggravating effect on IBD and IBD is a known risk factor for CDI. The colonic involvement in IBD not only renders the host more prone to an initial CDI development but also to further recurrences. Furthermore, IBD flares, which are predominantly set off by a CDI, not only create a need for therapy escalation but also prolong hospital stay. For these reasons, adequate and comprehensive management of CDI is of paramount importance in patients with IBD. Microbiological diagnosis, correct evaluation of clinical status, and consideration of different treatment options (from antibiotics and fecal microbiota transplantation to monoclonal antibodies) carry pivotal importance. Thus, the aim of this article is to review the risk factors, diagnosis, and management of CDI in patients with IBD.

A Retrospective Analysis of Intravenous vs Oral Antibiotic Step-Down Therapy for the Treatment of Uncomplicated Streptococcal Bloodstream Infections.

Evidence supporting intravenous-to-oral (IV-to-PO) antibiotic deescalation for uncomplicated streptococcal bloodstream infections (BSIs) are limited. The objective of this study was to compare clinical outcomes of patients treated with IV-only versus IV-to-PO antibiotic therapy for uncomplicated streptococcal BSIs. This was a single-center, retrospective study of patients aged ≥18 years who received treatment for uncomplicated streptococcal BSIs from January 2017 to December 2019. Patients were excluded if they had a polymicrobial BSI, endocarditis, osteomyelitis, septic arthritis, or received antibiotic therapy for >14 days. The primary outcome was clinical failure, defined as persistent bacteremia, recurrence of bacteremia, or mortality at 30 days. Secondary outcomes included length of hospital stay, all-cause readmissions, development of Clostridioides difficile infection, and adverse antibiotic reactions. There were 98 patients who met the inclusion criteria: 51 patients in the IV-to-PO therapy group and 47 patients who received IV-only antibiotics. Streptococcus pneumoniae and beta-hemolytic streptococci were the most common pathogens. Patients received an average of 4.4 days of IV antibiotics before being stepped down to an oral agent. Hospital length of stay (6.3 vs 12.6 days; P < .001) and total antibiotic duration of therapy (11.8 vs 13.9 days; P = .002) were significantly shorter in patients receiving IV-to-PO therapy. There were no clinical failures observed in patients who received IV-to-PO antibiotic therapy. IV-to-PO step-down therapy for uncomplicated streptococcal BSIs was not associated with worse clinical outcomes compared to patients receiving IV-only antibiotic therapy.

Association of fluoroquinolones or cephalosporin plus macrolide with Clostridioides difficile infection (CDI) after treatment for community-acquired pneumonia.

Clostridioides difficile infection (CDI) is the most common cause of gastroenteritis, and community-acquired pneumonia (CAP) is the most common infection treated in hospitals. American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) CAP guidelines recommend empiric therapy with a respiratory fluoroquinolone or cephalosporin plus macrolide combination, but the CDI risk of these regimens is unknown. We examined the association between each antibiotic regimen and the development of hospital-onset CDI. We conducted a retrospective cohort study using data from 638 US hospitals contributing administrative including 177 also contributing microbiologic data to Premier, Inc. We included adults admitted with pneumonia and discharged from July 2010 through June 2015 with a pneumonia diagnosis code who received ≥3 days of either empiric regimen. Hospital-onset CDI was defined by a diagnosis code not present on admission and positive laboratory test on day 4 or later or readmission for CDI. Mixed propensity-weighted multiple logistic regression was used to estimate the associations of CDI with antibiotic regimens. Our sample included 58,060 patients treated with either cephalosporin plus macrolide (36,796 patients) or a fluoroquinolone alone (21,264 patients) and with microbiological data; 127 (0.35%) patients who received cephalosporin plus macrolide and 65 (0.31%) who received a fluoroquinolone developed CDI. After adjustment for patient demographics, comorbidities, risk factors for antimicrobial resistance, and hospital characteristics, CDI risks were similar for fluoroquinolones versus cephalosporin plus macrolide (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.70-1.38). Among patients with CAP at US hospitals, CDI was uncommon, occurring in ∼0.33% of patients. We did not detect a significant association between the choice of empiric guideline recommended antibiotic therapy and the development of CDI.

Disordered Intestinal Microbial Communities During Clostridioides difficile Colonization and Subsequent Infection of Hepatic Cirrhosis Patients in a Tertiary Care Hospital in China.

Patients with hepatic cirrhosis are more susceptible to Clostridioides difficile infection (CDI) and colonization with Clostridioides difficile (C. difficile). Asymptomatic C. difficile colonization is thought to predispose to subsequent CDI. However, the dynamic gut microbiota changes remain unclear. In this study, we used 16S rRNA gene sequencing to longitudinally monitor alterations in the intestinal microbiota of 22 hepatic cirrhosis patients with toxigenic C. difficile colonization at admission (pre-CDI) and developed CDI during hospitalization, subdivided into pre-CDI and CDI. 21 hospitalized cirrhotic patients without C. difficile colonization served as controls (HC). Compared with HC, pre-CDI and CDI samples had significantly decreased microbial richness and diversity, a significantly higher relative abundance of opportunistic pathogen Enterococcus, and a lower relative abundance of beneficial symbionts, such as Faecalibacterium, Dorea, and Roseburia. Three biomarkers showed high accuracy for distinguishing pre-CDI samples from HC with an area under the curve (AUC) up to 0.81. In conclusion, our study explored the changes of the gut microbiome before and after CDI. The gut microbial richness as well as diversity in CDI patients were notably reduced, relative to controls. Imbalance of the intestinal flora may be related to the risk for development of CDI. Identifying key members of the gut microbiota and illustrating their roles and mechanisms of action in CDI development are important avenues for future research.

Clostridioides difficile Infection Is Associated with Adverse Outcomes among Hospitalized Pediatric Patients with Acute Pancreatitis.

PurposeStudies in adults have shown an increasing incidence of Clostridioides difficile infection (CDI) in patients hospitalized with acute pancreatitis (AP). There is lack of epidemiological data on CDI and its impact on hospitalized pediatric patients with AP.MethodsWe analyzed the National Inpatient Sample and Kids' Inpatient Database between the years 2003 and 2016 and included all patients (age <21 years) with a primary diagnosis of AP using specific International Classification of Diseases codes. We compared clinical outcomes between children with CDI and those without CDI. Our primary outcome was severe AP and secondary outcomes included length of stay and hospital charges.ResultsA total of 123,240 hospitalizations related to AP were analyzed and CDI was noted in 0.6% of the hospital. The prevalence rate of CDI doubled from 0.4% (2003) to 0.8% (2016), p=0.03. AP patients with CDI had increased comorbidities, and also underwent more invasive surgical procedures, p<0.05. AP patients with CDI had a higher in-hospital mortality rate and increased prevalence of severe AP, p<0.001. Multivariate regression models showed that CDI was associated with 2.4 times (confidence interval [CI]: 1.91 to 3.01, p<0.001) increased odds of severe AP. CDI patients had 7.24 (CI: 6.81 to 7.67, p<0.001) additional hospital days while incurring $59,032 (CI: 54,050 to 64,014, p<0.001) additional hospitalization charges.ConclusionCDI in pediatric patients with AP is associated with adverse clinical outcomes and increased healthcare resource utilization. Further studies are needed to elucidate this association to prevent the development of CDI and to improve outcomes.