Risk Of Clostridioides Difficile Infection Research Articles

Influence of Antibiotic Exposure Intensity on the Risk of Clostridioides difficile Infection.

Antibiotics are a strong risk factor for Clostridioides difficile infection (CDI), and CDI incidence is often measured as an important outcome metric for antimicrobial stewardship interventions aiming to reduce antibiotic use. However, risk of CDI from antibiotics varies by agent and dependent on the intensity (i.e., spectrum and duration) of antibiotic therapy. Thus, the impact of stewardship interventions on CDI incidence is variable, and understanding this risk requires a more granular measure of intensity of therapy than traditionally used measures like days of therapy (DOT). We performed a retrospective cohort study to measure the independent association between intensity of antibiotic therapy, as measured by the antibiotic spectrum index (ASI), and hospital-associated CDI (HA-CDI) at a large academic medical center between January 2018 and March 2020. We constructed a marginal Poisson regression model to generate adjusted relative risks for a unit increase in ASI per antibiotic day. We included 35,457 inpatient encounters in our cohort. Sixty-eight percent of patients received at least one antibiotic. We identified 128 HA-CDI cases, which corresponds to an incidence rate of 4.1 cases per 10,000 patient-days. After adjusting for known confounders, each additional unit increase in ASI per antibiotic day is associated with 1.09 times the risk of HA-CDI (Relative Risk = 1.09, 95% Confidence Interval: 1.06 to 1.13). ASI was strongly associated with HA-CDI and could be a useful tool in evaluating the impact of antibiotic stewardship on HA-CDI rates, providing more granular information than the more commonly used days of therapy.

SER-109 (VOWST™): A Review in the Prevention of Recurrent Clostridioides difficile Infection.

SER-109 (VOWST™; fecal microbiota spores, live-brpk) is a live biotherapeutic product indicated to prevent the recurrence of Clostridioides difficile infection (CDI) in patients 18years of age and older following standard of care (SOC) antibacterial treatment for recurrent CDI. It is a purified bacterial spore suspension sourced from healthy donors. As the first oral faecal microbiota product approved for prevention of recurrent CDI, SER-109 is administered as four capsules once daily for three consecutive days. In a well-designed, placebo-controlled, phaseIII trial (ECOSPORIII), SER-109 significantly reduced the risk of recurrent CDI at 8weeks post-treatment, with a durable response seen at 6months post-treatment. Treatment with SER-109 was also associated with rapid and steady improvement in health-related quality of life compared with placebo. SER-109 was generally well tolerated, with a safety profile similar to that of placebo. The most common adverse events were of mild to moderate severity and generally gastrointestinal in nature. Thus, with the convenience of oral administration and lack of necessity for cold storage, SER-109 is a valuable option for preventing further CDI recurrence in adults following antibacterial treatment for recurrent CDI.

The Role of Probiotics in the Prevention of Clostridioides difficile Infection in Patients with Chronic Kidney Disease.

In patients suffering from chronic kidney disease (CKD), substantial unfavourable alterations in the intestinal microbiota composition, i.e., dysbiosis, have been noted. The main causes of such dysbiosis among others are insufficient dietary fibre content in the diet, fluid restrictions, medications used, and physical activity limitation. One clinically important consequence of dysbiosis in CKD patients is high risk of Clostridioides difficile infection (CDI). In observational studies, it was found that CDI is more frequent in CKD patients than in the general population. This appears to be related to high hospitalization rate and more often antibiotic therapy use, leading up to the occurrence of dysbiosis. Therefore, the use of probiotics in CKD patients may avert changes in the intestinal microbiota, which is the major risk factor of CDI. The aim of this review paper is to summarize the actual knowledge concerning the use of probiotics in CDI prevention in CKD patients in the context of CDI prevention in the general population.

A Real-World Study on the Clinical Characteristics, Outcomes, and Relationship between Antibiotic Exposure and Clostridioides difficile Infection.

Clostridioides difficile is a Gram-positive bacteria that causes nosocomial infections, significantly impacting public health. In the present study, we aimed to describe the clinical characteristics, outcomes, and relationship between antibiotic exposure and Clostridioides difficile infection (CDI) in patients based on reports from two databases. Thus, we conducted a retrospective study of patients diagnosed with CDI from Sibiu County Clinical Emergency Hospital (SCCEH), Romania, followed by a descriptive analysis based on spontaneous reports submitted to the EudraVigilance (EV) database. From 1 January to 31 December 2022, we included 111 hospitalized patients with CDI from SCCEH. Moreover, 249 individual case safety reports (ICSRs) from EVs were analyzed. According to the data collected from SCCEH, CDI was most frequently reported in patients aged 65-85 years (66.7%) and in females (55%). In total, 71.2% of all patients showed positive medical progress. Most cases were reported in the internal medicine (n = 30, 27%), general surgery (n = 26, 23.4%), and infectious disease (n = 22, 19.8%) departments. Patients were most frequently exposed to ceftriaxone (CFT) and meropenem (MER). Also, in the EV database, most CDI-related ADRs were reported for CFT, PIP/TAZ (piperacillin/tazobactam), MER, and CPX (ciprofloxacin). Understanding the association between previous antibiotic exposure and the risk of CDI may help update antibiotic stewardship protocols and reduce the incidence of CDI by lowering exposure to high-risk antibiotics.

A Systematic Literature Review on Risk Factors for and Timing of Clostridioides difficile Infection in the United States.

Clostridioides difficile infection (CDI) is a major public health threat. Up to 40% of patients with CDI experience recurrent CDI (rCDI), which is associated with increased morbidity. This study aimed to define an at-risk population by obtaining a detailed understanding of the different factors leading to CDI, rCDI, and CDI-related morbidity and of time to CDI. We conducted a systematic literature review (SLR) of MEDLINE (using PubMed) and EMBASE for relevant articles published between January1, 2016, and November11, 2022, covering the US population. Of the 1324 articles identified, 151 met prespecified inclusion criteria. Advanced patient age was a likely risk factor for primary CDI within a general population, with significant risk estimates identified in nine of 10 studies. Older age was less important in specific populations with comorbidities usually diagnosed at earlier age, such as bowel disease and cancer. In terms of comorbidities, the established factors of infection, kidney disease, liver disease, cardiovascular disease, and bowel disease along with several new factors (including anemia, fluid and electrolyte disorders, and coagulation disorders) were likely risk factors for primary CDI. Data on diabetes, cancer, and obesity were mixed. Other primary CDI risk factors were antibiotics, proton pump inhibitors, female sex, prior hospitalization, and the length of stay in hospital. Similar factors were identified for rCDI, but evidence was limited. Older age was a likely risk factor for mortality. Timing of primary CDI varied depending on the population: 2-3weeks in patients receiving stem cell transplants, within 3weeks for patients undergoing surgery, and generally more than 3weeks following solid organ transplant. This SLR uses recent evidence to define the most important factors associated with CDI, confirming those that are well established and highlighting new ones that could help to identify patient populations at high risk.

The combined effect of systemic antibiotics and proton pump inhibitors on Clostridioides difficile infection and recurrence.

Antibiotics and proton pump inhibitors (PPI) are recognized risk factors for acquisition and recurrence of Clostridioides difficile infection (CDI), yet combined effects remain unclear. To assess the short- and long-term effects of antibiotics and PPIs on CDI risk and recurrence. Population-based study including all 43 152 patients diagnosed with CDI in Sweden (2006-2019), and 355 172 matched population controls without CDI. The impact of antibiotics and PPIs on CDI risk and recurrence was explored for recent (0-30 days) and preceding (31-180 days) use prior to their first CDI diagnosis, using multivariable conditional logistic regression presented as odds ratios (ORs) and 95% confidence interval, adjusted for demographics, comorbidities and other drugs. Compared to controls, the combined effect of recent PPIs and antibiotics [ORAB+PPI = 17.51 (17.48-17.53)] on CDI risk was stronger than the individual effects [ORAB = 15.37 (14.83-15.93); ORPPI = 2.65 (2.54-2.76)]. Results were less pronounced for exposure during the preceding months. Dose-response analyses showed increasing exposure correlated with CDI risk [recent use: ORAB = 6.32 (6.15-6.49); ORPPI = 1.65 (1.62-1.68) per prescription increase].Compared to individuals without recurrence (rCDI), recent [ORAB = 1.30 (1.23-1.38)] and preceding [ORAB = 1.23 (1.16-1.31); ORPPI = 1.12 (1.03-1.21)] use also affected the risk of recurrence yet without significant interaction between both. Recent macrolides/lincosamides/streptogramins; other antibacterials including nitroimidazole derivates; non-penicillin beta lactams and quinolones showed the strongest association with CDI risk and recurrence, particularly for recent use. PPI use, both recent and preceding, further increased the CDI risk associated with almost all antibiotic classes. Recent and less recent use of PPIs and systemic antibiotics was associated with an increased risk of CDI, particularly in combination.

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<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<0.001) and short disease duration (1.08, CI 95% 1.04- 1.13, P<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.

Inappropriate treatment of asymptomatic bacteriuria

Asymptomatic bacteriuria is frequently encountered in clinical practice and should be treated only in pregnant women and before invasive urological procedures. Inappropriate treatment of asymptomatic bacteriuria is associated with numerous adverse effects including allergic reactions, increased antibiotics resistance and increase risk of Clostridioides difficile infection. Positive urinary culture often leads to antimicrobial treatment, irrespective of urinary symptoms. Therefore, urine analysis and culture should be performed only in symptomatic individuals or in asymptomatic individuals with a clear indication for treatment.

Application of the U.S. Food and Drug Administration's Sentinel Routine Querying Tools to the Taiwan Sentinel Data Model-formatted National Health Insurance Research Database.

The U.S. Food and Drug Administration's Sentinel System is a leading distributed data network for drug safety surveillance in the world. The National Health Insurance Research Database (NHIRD) in Taiwan was converted into the Taiwan Sentinel Data Model (TSDM) based on the Sentinel Common Data Model (SCDM) version 6.0.2. The goal of this study was to investigate the feasibility of applying the same study designs, analytic choices, and analytic tools as used by the U.S. Sentinel System to examine the same drug-outcome associations in the TSDM-formatted NHIRD. Four known drug-outcome associations previously examined by the U.S. Sentinel System were selected as the use cases: (1) use of angiotensin-converting enzyme inhibitors (ACEIs) and risk of angioedema, (2) use of warfarin and risk of gastrointestinal bleeding, (3) use of oral clindamycin and risk of Clostridioides difficile infection (CDI), and (4) use of glyburide and risk of serious hypoglycemia. We followed the same study designs and analytic choices used by the U.S. Sentinel System and applied the Sentinel Routine Querying Tools to answer the same study questions within the TSDM-formatted NHIRD. The results showed that ACEIs were associated with a non-significant increase in risk of angioedema compared to beta-blockers (hazard ratio [HR]: 1.21; 95% confidence interval [CI]: 0.89-1.64); warfarin was associated with a higher risk of gastrointestinal bleeding compared to statins (HR: 1.72; 1.50-1.98); glyburide was associated with an increased risk of hypoglycemia compared to glipizide (HR: 1.61, 1.30-2.00). We were unable to evaluate the association between oral clindamycin and risk of CDI due to the low event number. Our study demonstrated that it was feasible to directly apply the publicly available Sentinel Routine Querying Tools within the TSDM-formatted NHIRD. However, sources of heterogeneity other than design and analytic differences should be carefully considered when comparing the results between the two systems.

696. Effectiveness of Oral Vancomycin as Prophylaxis against Clostridioides difficile Infection in Hematopoietic Stem Cell Transplant Patients

Abstract Background Patients receiving hematopoietic stem cell transplants (HSCT) are at increased risk for Clostridioides difficile infection (CDI) due to decreased immune function, frequent exposure to broad-spectrum antibiotics and chemotherapy, prolonged hospitalizations, and alteration in gut microbiome. The purpose of this study was to assess the effectiveness of oral vancomycin prophylaxis (OVP) for CDI in all patients admitted for HSCT. Methods This was a single-center, retrospective, cohort study conducted at a tertiary care academic medical center in New Jersey. Medical records of patients admitted between June 2019 to August 2022 to undergo an allogeneic or autologous HSCT were reviewed. Universal OVP from admission to discharge for HSCT patients began December 2019. Patients ≥ 18 years at the time of admission for the HSCT were included. Patients who were admitted less than 72 hours or who were being treated for an active CDI prior to HSCT were excluded. The primary endpoint was the incidence of in-hospital CDI. Secondary endpoints included incidence of vancomycin-resistant enterococci (VRE) bloodstream infections, VRE isolated from any clinical culture, gram-negative bloodstream infections, hospital survival, and hospital length of stay. Exploratory endpoints including one-year survival, relapse, and incidence of graft-versus-host disease were also collected. Confounding by relevant covariates were assessed and controlled for in a multivariable regression model. Results A total of 132 HSCT patients were included. There was one case (1/68, 1.47%) of CDI in the prophylaxis group compared to six CDI cases (6/64, 9.38%) in the no prophylaxis group (P=0.057). There were no significant (P>0.05) between-group differences of incidence of gram-negative bloodstream infections, hospital survival, and length of stay. There were zero clinical cultures positive for VRE in either group. Conclusion In-hospital incidence of CDI in HSCT patients was decreased with the use of OVP but did not meet statistical significance. Randomized controlled trials are needed in this high-risk patient population to assess the efficacy and long-term risks of OVP for CDI. Disclosures Pinki Bhatt, MD, Sanofi: Grant/Research Support Navaneeth Narayanan, PharmD, MPH, BCIDP, Astellas: Honoraria|Beckman Coulter: Honoraria|Merck: Grant/Research Support|Shionogi: Grant/Research Support

Proton pump inhibitor (PPI) administration and Clostridioides difficile infection - is this a real clinical problem? A critical review of the literature

Background: Proton pump inhibitors (PPIs) are widely used drugs that reduce gastric acid secretion. In recent years, there has been a gradual increase in their use. The safety of prolonged PPI therapy and the potential for cumulative side effects of these drugs raise legitimate concerns. An association between PPI administration and the risk of Clostridioides difficile infection has been suggested. The findings regarding this phenomenon require further unequivocal verification.
 Material and methods: A review of publications obtained from the PubMed database and published between 2016-2023. Based on the keywords "proton pump inhibitor", "PPI" and "Clostridium", 132 articles were selected. Finally, 6 meta-analyses were included in the analysis.
 Results: Studies conducted in recent years have shown a statistically significant increase in the risk of C. difficile infection in patients taking PPIs compared to those who avoid this therapy. The aforementioned relationship was observed in both adults and pediatric patients. One study proved that the risk remained high even up to 1 year after the end of treatment. The described relationship is still a matter of debate due to the fact that patients using antacids are usually elderly, have several comorbidities and a higher risk of developing C. difficile infection regardless of PPI use.
 Conclusions: The relationship between the use of PPIs and the risk of developing C. difficile infection is still controversial, which justifies the need for continued clinical trials to objectively resolve this issue. PPIs exert high efficacy in the treatment of acid-dependent diseases, but due to the many ambiguities surrounding possible side effects, caution in their administration seems warranted, especially for long-term therapy in elderly patients with polypharmacy.

Effect of Respiratory Viral Panel Adoption on Antibiotic Use in Ventilated Patients.

Rationale: Rapid respiratory viral panel (RVP) testing has become widely used to aid in the diagnosis and treatment of acute respiratory failure. However, the impact of RVP on antibiotic stewardship in critically ill patients is unclear. Objectives: To assess if adoption of RVP testing at hospitals was associated with changes in antibiotic duration in intensive care unit patients receiving invasive mechanical ventilation. Methods: With data from the Premier Inc. database from 2016 to 2019, we used interrupted time series with multivariable hierarchical linear regression models to quantify trends in outcomes for 31,644 patients in the 12 months before RVP adoption, the level change in outcomes at the time of RVP adoption (estimand of interest), and changes in outcome trends in the 12 months after RVP adoption. Results: Hospital adoption of RVP testing (n = 62,603) was associated with a decrease in days of antibiotics by 0.5 days (95% confidence interval, -0.8, -0.1) in the first month after adoption. There was also a significant decrease in the risk of Clostridioides difficile infection by 0.9% (95% confidence interval, -1.6, -0.3). There were no significant changes in other outcomes, including hospitalization costs, hospital length of stay, or rates of ventilator-associated pneumonia. Conclusions: Hospital adoption of RVP testing was associated with modest reductions in both antibiotic duration and risk of C. difficile infection among intensive care unit patients with acute respiratory failure and suspected infection.

A retrospective study investigating the management, risk factors, and outcomes of patients diagnosed with Clostridioides difficile infection

AbstractBackgroundThe rate of clostridioides difficile infection (CDI) in Australia has increased by more than 8% between 2016–2018. This can be attributed to multiple factors including an ageing population, widespread antibiotic and proton‐pump‐inhibitor usage.AimThe aim of this study was to investigate the management, risk factors and outcomes for CDI to identify strategies to reduce its incidence.MethodA single‐centre retrospective audit was completed using medical records for patients admitted to a 250‐bed regional Queensland hospital with CDI in 2020–2021. Data surrounding CDI management for each patient was analysed against the Therapeutic Guidelines. This study was approved by The Prince Charles Hospital Human Research Ethics Committee (Reference No: LNR/HREC/QPCH/81287).ResultsThere were 72 cases with CDI during the study timeframe. Recent antibiotic prescription, proton‐pump‐inhibitor (PPI) use and antibiotic allergy labels were common. Thirty‐five per cent of cases were treated appropriately. Eight per cent died, and nine per cent had relapsed CDI within 12 weeks of diagnosis. Common gaps found in the results included inappropriate selection of antibiotics based on the severity of disease and lack of documentation surrounding CDI cases left untreated.ConclusionThere are multiple opportunities for pharmacists to improve the care of patients with CDI which range from promoting guideline adherence, influencing prescriber antibiotic selection based on disease severity, prompting review of PPIs upon CDI diagnosis and prompting provider follow‐up of CDI laboratory results pending at the point of patient discharge. The results of this study have prompted antimicrobial stewardship service review of all CDI admissions at the study site and indicates the need for a larger multiple‐site study to raise awareness of CDI risk factors and severity criteria.

Clostridioides difficile infection in a skilled nursing facility (SNF): cost savings of an automated, standardized probiotic antimicrobial stewardship programme (ASP) policy.

With multiple comorbidities and frequent exposures to antibiotics, patients in skilled nursing facilities (SNFs) are much more vulnerable to healthcare-acquired infections. We conducted a quality-improvement, retrospective analysis of all patients with Clostridioides difficile infection (CDI) from 2009 to 2021 at an SNF. Probiotics were initially added to a bundle of antimicrobial stewardship programme (ASP) CDI prevention strategies. Formulations and durations of probiotics were standardized for both oral and enteral administration. To reach all eligible patients, an ASP probiotic policy provided probiotics with every antibiotic course. To assess the value of providing probiotic therapy to SNF patients at risk for CDI. Patients receiving oral or enteral feeding with antibiotics ordered were eligible to receive probiotics. The incremental cost of CDI prevention, treatment and related care were calculated and compared for each phase of probiotic policy change and feeding type. ASP records for the oral probiotic and level of treatment were used in modelling the cost-effectiveness. From quality improvement initiatives aimed at preventing facility-onset (FO) CDI, to ASP policies, probiotic formulations and delegation of ordering authority, the days of acute care treatment required was significantly reduced over the different phases of implementation [152 to 48, OR = 0.22 (0.16-0.31) to 4, OR = 0.08 (0.03-0.23)] after reducing total CDI from 5.8 to 0.3 cases per 10 000 patient-days. The annual cost of oral probiotics increased from $6019 to $14 652 but the modelled net annual savings for the facility was $72 544-$154 085. With optimization, the use of probiotics for CDI prevention at an SNF was safe, efficacious and cost-effective.

ANTIDEPRESSANT MEDICATIONS ARE ASSOCIATED WITH INCREASED RISK OF HOSPITAL-ACQUIRED CLOSTRIDIOIDES DIFFICILE INFECTION: A POPULATION-BASED STUDY.

•The rate and severity of Clostridioides difficile infection (CDI) has increased throughout North America, the United Kingdom, and Europe. •Scattered evidence about the association of CDI with antidepressant medications use exists in the literature so far. What are the new findings: •The risk of Clostridioides difficile infection is higher in patients who are on mirtazapine, nortriptyline, or trazodone. •The prevalence rate of Clostridioides difficile infection in patients who were using antidepressant medications and the ones who did not, increased with age. Background - During the past decade, Clostridioides difficile infection (CDI) has become the most common cause of antibiotic-associated diarrhea. Several risk factors have been implicated. Scattered evidence about the association of CDI with antidepressant medications use exists in the literature so far. Therefore, we aim to investigate whether the risk of developing CDI is increased in hospitalized patients using antidepressant medications.Methods - Patients who were hospitalized were included in our cohort. We excluded individuals aged less than 18 years. A multivariate regression analysis was performed to calculate the risk of CDI accounting for potential confounders. Results - The risk of CDI in hospitalized patients was increased in individuals diagnosed with inflammatory bowel disease (OR: 4.44; 95%CI: 4.35-4.52), and in patients using clindamycin (OR: 1.55; 95%CI: 1.53-1.57), beta-lactam antibiotics (OR: 1.62; 95%CI: 1.60-1.64), PPI (OR: 3.27; 95%CI: 3.23-3.30), trazodone (OR: 1.31; 95%CI: 1.29-1.33), nortriptyline (OR: 1.25; 95%CI: 1.21-1.28), and mirtazapine (OR: 2.50; 95%CI: 2.46-2.54). After controlling for covariates, the risk of CDI was not increased in patients who were taking fluoxetine (OR: 0.94; 95%CI: 0.92-0.96). Conclusion - In contrary to fluoxetine; mirtazapine, nortriptyline, and trazodone were associated with increased risk of CDI in hospitalized patients.

Implementation of routine Clostridioides difficile infection (CDI) primary prophylaxis in lung transplant recipients.

Lung transplant recipients are at an increased risk for Clostridioides difficile infection (CDI), and those who develop CDI post-transplant can have worsened outcomes including graft failure and death. We sought to describe the efficacy and safety of primary CDI prophylaxis with oral vancomycin among 86 adult lung transplant recipients. Overall, we observed a 9.3% (8/86) incidence of CDI among patients receiving prophylaxis, with the majority of infections occurring a median of 25 days after completion of prophylaxis. Furthermore, we observed a 4.7% incidence of VRE infection/colonization. Opportunities exist to optimize the duration of CDI prophylaxis to balance the benefits and risks in lung transplant recipients.

A new score to predict Clostridioides difficile infection in medical patients: a sub-analysis of the FADOI-PRACTICE study.

Medical divisions are at high risk of Clostridioides difficile infection (CDI) due to patients' frailty and complexity. This sub-analysis of the FADOI-PRACTICE study included patients presenting with diarrhea either at admission or during hospitalization. CDI diagnosis was confirmed when both enzyme immunoassay and A and B toxin detection were found positive. The aim of this sub-analysis was the identification of a new score to predict CDI in hospitalized, medical patients. Five hundred and seventy-two patients with diarrhea were considered. More than half of patientswas female, 40% on antibiotics in the previous 4weeks and 60% on proton pump inhibitors(PPIs). CDI diagnosis occurred in 103 patients (18%). Patients diagnosed with CDI were older, more frequently offemalesex, recently hospitalized and bed-ridden, and treated with antibiotics and PPIs. Through a backward stepwise logistic regression model, age > 65years, female sex, recent hospitalization, recentantibiotic therapy, active cancer, prolonged hospital stay (> 12days), hypoalbuminemia (albumin < 3g/dL), and leukocytosis (white blood cells > 9 × 10^9/L) were found to independently predict CDI occurrence. These variables contributed to building a clinical prognostic score with a good sensitivity and a modest specificity for a value > 3 (79% and 58%, respectively; AUC 0.75, 95% CI 0.71-0.79, p < 0.001), that identified low-risk (score ≤ 3; 42.5%) and high-risk (score > 3; 57.5%) patients. Although some classical risk factors were confirmed to increase CDI occurrence, the changing landscape of CDI epidemiology suggests a reappraisal of common risk factors and the development of novel risk scores based on local epidemiology.

Risk of Gastrointestinal Infections After Initiating Vedolizumab and Anti-TNFα Agents for Ulcerative Colitis.

Characterize and compare the risk of Clostridioides difficile infection (CDI) and cytomegalovirus colitis (CMVC) after initiation of vedolizumab or anti-tumor necrosis factor (TNF)α agents for ulcerative colitis (UC). Immunosuppression is a risk factor for gastrointestinal infections including CDI and CMVC among patients with UC; however, the risk according to the biological class is poorly understood. A retrospective cohort study of adults with UC involving the initiation of vedolizumab or anti-TNFα agents during June 1, 2014 to December 31, 2020 was conducted at a large academic health system. The primary outcomes for both CDI and CMVC analyses were first CDI or CMVC after biological initiation. The secondary outcome for the CDI analysis was severe CDI (>10,000 white blood cells or serum creatinine >1.5mg/dL). Independent variables included demographics and UC history/severity factors. Inverse probability of treatment weighted Cox regression was performed to assess the hazard of CDI by biological group. Due to few outcomes, CMVC was reported descriptively. A total of 805 UC patients initiated vedolizumab (n=195) or anti-TNFα agents (n=610). There were 43 CDIs and 11 severe CDIs over 1436 patient-years. The inverse probability of treatment weighted Cox regression demonstrated no association between CDI and vedolizumab versus anti-TNFα (hazard ratio 0.33, 95% confidence interval 0.05-2.03), but identified a significantly lower hazard of severe CDI for vedolizumab versus anti-TNFα (hazard ratio 0.10, 95% confidence interval 0.01-0.76). There were 5 cases of CMVC, all in the anti-TNFα group. There was a lower adjusted risk of severe CDI but not total CDI associated with vedolizumab. CMVC was not observed after initiating vedolizumab. These findings may provide reassurance regarding the use of vedolizumab when also considering the risk of gastrointestinal infections.

Comparison of Different Antibiotics and the Risk for Community-Associated Clostridioides difficile Infection: A Case-Control Study.

Antibiotics are the greatest risk factor for Clostridioides difficile infection (CDI). Risk for CDI varies across antibiotic types and classes. Optimal prescribing and stewardship recommendations require comparisons of risk across antibiotics. However, many prior studies rely on aggregated antibiotic categories or are underpowered to detect significant differences across antibiotic types. Using a large database of real-world data, we evaluate community-associated CDI risk across individual antibiotic types. We conducted a matched case-control study using a large database of insurance claims capturing longitudinal health care encounters and medications. Case patients with community-associated CDI were matched to 5 control patients by age, sex, and enrollment period. Antibiotics prescribed within 30 days before the CDI diagnosis along with other risk factors, including comorbidities, health care exposures, and gastric acid suppression were considered. Conditional logistic regression and a Bayesian analysis were used to compare risk across individual antibiotics. A sensitivity analysis of antibiotic exposure windows between 30 and 180 days was conducted. We identified 159 404 cases and 797 020 controls. Antibiotics with the greatest risk for CDI included clindamycin and later-generation cephalosporins, and those with the lowest risk included minocycline and doxycycline. We were able to differentiate and order individual antibiotics in terms of their relative level of associated risk for CDI. Risk estimates varied considerably with different exposure windows considered. We found wide variation in CDI risk within and between classes of antibiotics. These findings ordering the level of associated risk across antibiotics can help inform tradeoffs in antibiotic prescribing decisions and stewardship efforts.

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.