Clostridioides difficile is a leading cause of healthcare-associated infection, and an unacceptably high proportion of patients with C. difficile infection die despite conventional antibiotic treatment. Host-directed immunotherapy has been proposed as an ideal treatment modality for C. difficile infection to mitigate the underlying toxin-mediated pathogenic immune response while sparing protective gut microbes. Interleukin-23 monoclonal antibody inhibitors are used extensively to control pro-inflammatory Th17 immune pathways in psoriasis and inflammatory bowel disease that are similarly important during C. difficile infection. We used a large retrospective electronic health record database to test the hypothesis that hospitalized patients with C. difficile infection who are on anti-IL-23 treatment will have improved survival compared to patients without anti-IL-23. A total of 9,301 anti-IL-23 patients had significantly lower probability of all-cause death within 30 d (0.54%) compared with 1:1 propensity-matched control patients (3.1%). IL-23 inhibition is a promising adjunct to C. difficile treatment, and further clinical trials repositioning anti-IL-23 monoclonal antibodies from psoriasis and inflammatory bowel disease to C. difficile infection are warranted.

Current treatments against Clostridium difficile infection (CDI), such as vancomycin and metronidazole, frequently lead to severe recurrence due to disruption of gut microbiota balance, which results in a pressing need for new chemical entities to treat CDI. Bile acids, such as UDCA, have been demonstrated to inhibit the growth and spore germination of C. difficile, and regulate the structure of the intestinal flora. This study involved the synthesis of eight bile acid-metronidazole hybrids. Among them, the most promising hybrid, SCUT1-2, effectively killed the vegetative cells of C. difficile with a minimum inhibitory concentration (MIC) of 0.06-0.50 μg/mL, and inhibited spore germination in vitro. The absolute bioavailability of SCUT1-2 (F = 56.8 %) indicated that approximately half of SCUT1-2 was absorbed systemically, while a considerable portion remained in the gastrointestinal tract in its original form, laying a solid foundation for its effective action in vivo. SCUT1-2 could effectively alleviate the symptoms of weight loss and diarrhea in mice caused by CDI and effectively reduce the relevant expressions of inflammatory factors, outperforming metronidazole. Furthermore, SCUT1-2 demonstrated a favorable therapeutic effect in reducing mortality and disease symptoms in CDI mice by killing C. difficile cells and regulating the composition and structure of the intestinal flora. Notably, SCUT1-2 could effectively prevent recurrent CDI. This work provides a potential clinical lead for the development of CDI therapies and highlights hybrid medication as a new strategy.

Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated diarrhea. Recurrence occurs in up to 60 % of patients following multiple episodes, posing a major clinical challenge. While vancomycin (VCM) and fidaxomicin (FDX) are recommended first-line therapies, treatment failures and recurrences are not uncommon. Extended-pulsed fidaxomicin (EPFX) has been proposed to reduce recurrence, especially in high-risk patients, though the evidence remains limited for those with multiple prior relapses. We report the case of a 66-year-old man with advanced esophageal and gastric cancer who experienced four episodes of recurrent CDI despite standard treatment with VCM and FDX. Given the unavailability of bezlotoxumab (BEZ) in Japan and the limited accessibility of fecal microbiota transplantation (FMT), EPFX was selected as a salvage regimen. After both EPFX and pulse-tapered oral VCM were explained, the patient and physician elected to initiate EPFX, consisting of 200 mg twice daily for five days followed by 200 mg every other day for 20 days. No further recurrences were observed for over four months, and no adverse effects were noted. This case supports the use of EPFX in patients with multiple high-risk features-including advanced age, active malignancy, and prior treatment failures-despite the EXTEND trial's exclusion of patients with ≥3 recurrences. The favorable pharmacokinetic properties of FDX may have contributed to its efficacy. Importantly, the patient's medication, nutritional, and oncologic status remained stable throughout treatment, suggesting that EPFX played a pivotal role in achieving remission. EPFX may offer a viable option for patients with recurrent CDI refractory to standard therapies.

Clostridioides difficile infection (CDI) and recurrent CDI (rCDI) are significant causes of morbidity and mortality. The microbiome plays a significant role in the body's defense against CDI and rCDI. Antibiotics can cause significant injury to the microbiome which leads to an increased risk of CDI and rCDI. Ongoing perturbations of the microbiome perpetuate this risk. Antibiotic treatments for CDI can kill C difficile but also can impact the microbiome. Microbiome therapeutics are effective in restoring the function of the gut microbiota and re-establishing colonization resistance. The field of microbiome therapeutics is evolving with newer, more refined, modalities in development.

Refractory malignant ascites in the advanced palliative phase significantly impacts patients' quality of life (QoL), causing pain, respiratory difficulties, digestive issues, and impaired mobility. While iterative drainages can effectively relieve symptoms, frequent hospital visits and the significant volume of fluid requiring removal pose considerable challenges. A semi-continuous approach using a permanent bedside drain may offer more frequent drainages of smaller volumes. This study aimed to examine the feasibility, reliability, and safety of a semi-permanent bedside abdominal drain for patients in advanced palliative care with refractory malignant ascites.

This is a retrospective study, with cases identified through computerized queries of digital patient records. Data collected included patient characteristics, biological parameters, procedure details, and end-of-life outcomes.

Between 2019 and 2024, this drain was proposed to 25 palliative care patients. They had received a median of three lines of oncological treatment, with 60% of them receiving exclusively palliative care at the time of drainage. Drain placement had a beneficial impact on disabling symptoms in over 92% of cases, allowing 60% of patients to return to home hospitalization, without requiring additional hospital visits for paracentesis. The median time between drain placement and end of life was 36.5 days [4;147], while the median time from the diagnosis of refractory ascites to death was 93.7 days [14;263].

A non-tunneled semi-permanent catheter, easily implanted at the patient's bedside, may improve QoL. This study serves as a pilot for a prospective cohort that will analyze QoL improvements and economic costs.

Clostridioides difficile infection (CDI) causes a significant national health care burden. Literature has demonstrated lower rates of CDI recurrence with fidaxomicin compared with oral vancomycin. However, patients are sometimes switched to oral vancomycin before completing a fidaxomicin course.

The objective of this study is to evaluate rates of CDI recurrence in full courses of fidaxomicin versus partial courses of fidaxomicin followed by a switch to oral vancomycin.

In this single-center, retrospective, cohort study of adults with CDI, patients were screened for inclusion if they received either a full 10-day course of fidaxomicin or partial course of fidaxomicin followed by a switch to oral vancomycin. The primary outcome was the rate of CDI recurrence within 30 days after completion of initial therapy determined by a positive CDI test and initiation of treatment.

Ninety-nine patients received a full course of fidaxomicin, and 95 patients received a partial course of fidaxomicin followed by oral vancomycin. Mean age was lower in the full course group compared with the partial course (65.3 years vs 71.5 years, P < 0.002). Clostridioides difficile infection recurrence occurred in 5.1% of the full course group and 7.4% of the partial therapy group (P = 0.503) at 30 days and 13.1% versus 14.7% (P = 0.747) at 90 days. Clostridioides difficile infection-related readmissions at 30 days were similar in the full course and partial course groups (7.1% vs 4.2%, P = 0.389).

Partial courses of fidaxomicin followed by oral vancomycin had similar 30-day CDI recurrence compared with full course fidaxomicin.

Background/Objective. Toxin-producing strains of Clostridioides difficile (C. diff) are the most commonly identified cause of healthcare-associated infection in the elderly. Risk factors include advanced age, hospitalization, prior or concomitant systemic antibacterial therapy, chemotherapy, and gastrointestinal surgery. Patients with unspecified and new-onset diarrhea with ≥3 unformed stools in 24 h are the target population for C. diff infection (CDI) testing. To present data on the risks of laboratory misdiagnosis in managing CDI. Materials. In two general hospitals, we examined 116 clinical stool specimens from hospitalized patients with acute diarrhea suspected of nosocomial or antibiotic-associated diarrhea (AAD) due to C. diff. Enzyme immunoassay (EIA) tests for the detection of C. diff toxins A (cdtA) and B (cdtB) in stool, automated CLIA assay for the detection of C. diff GDH antigen and qualitative determination of cdtA and B in human feces and anaerobic stool culture were applied for CDI laboratory diagnosis. MALDI-TOF (Bruker) was used to identify the presumptive anaerobic bacterial colonies. The following methods were used as confirmatory diagnostics: the LAMP method for the detection of Salmonella spp. and simultaneous detection of C. jejuni and C. coli, an E. coli Typing RT-PCR detection kit (ETEC, EHEC, STEC, EPEC, and EIEC), API 20E and aerobic stool culture methods. Results. A total of 40 toxigenic strains of C. diff were isolated from all 116 tested diarrheal stool samples, of which 38/40 produced toxin B and 2/40 strains were positive for both cdtA and cdtB. Of the stool samples positive for cdtA (6/50) and/or cdtB (44/50) by EIA, 33 were negative for C. diff culture but positive for the following diarrheal agents: Salmonella enterica subsp. arizonae (1/33, LAMP, culture, API 20E); C. jejuni (2/33, LAMP, culture, MALDI TOF); ETEC O142 (1/33), STEC O145 and O138 (2/33, E. coli RT-PCR detection kit, culture); C. perfringens (2/33, anaerobic culture, MALDI TOF); hypermycotic enterotoxigenic K. pneumonia (2/33) and enterotoxigenic P. mirabilis (2/33, culture; PCR encoding LT-toxin). Two of the sixty-six cdtB-positive samples (2/66) showed a similar misdiagnosis when analyzed using the CLIA method. However, the PCR analysis showed that they were cdtB-negative. In contrast, the LAMP method identified a positive result for C. jejuni in one sample, and another was STEC positive (stx1+/stx2+) by RT-PCR. We found an additional discrepancy in the CDI test results: EPEC O86 (RT-PCR eae+) was isolated from a fecal sample positive for GHA enzyme (CLIA) and negative for cdtA and cdtB (CLIA and PCR). However, the culture of C. diff was negative. These findings support the hypothesis that certain human bacterial pathogens that produce enterotoxins other than C. diff, as well as intestinal commensal microorganisms, including Klebsiella sp. and Proteus sp., contribute to false-positive EIA card tests for C. diff toxins A and B, which are the most widely used laboratory tests for CDI. Conclusions. CDI presents a significant challenge to clinical practice in terms of laboratory diagnostic management. It is recommended that toxin-only EIA tests should not be used as the sole diagnostic tool for CDI but should be limited to detecting toxins A and B. Accurate diagnosis of CDI requires a combination of laboratory diagnostic methods on which proper infection management depends.

Clostridioides difficile infection (CDI) is a leading cause of nosocomial infections in the United States, causing longer hospital stays, significant morbidity, and increased healthcare costs. Accurate CDI diagnosis is essential for timely treatment and infection control. Laboratory diagnosis of CDI commonly involves the detection of glutamate dehydrogenase (GDH) and/or toxins A and B by immunoassays or the toxin genes by nucleic acid amplification. This study assesses the performance of a new commercial test, the Sofia® 2 C. difficile Fluorescent Immunoassay (Sofia 2; FIA; QuidelOrtho), for detecting C. difficile GDH and toxins.

Sofia 2 was compared to enzyme immunoassays (EIAs) C. diff Quik Chek Complete (Techlab Inc.) and Immunocard (Meridian Bioscience) using remnant stool samples from 262 patients with suspected CDI.

Sofia 2 demonstrated high agreement with the EIA methods for GDH (positive percentage agreement (PPA): 100%, negative percentage agreement (NPA): 94%, overall percentage of agreement (OPA): 95%) and toxins (PPA: 100%, NPA: 99%, OPA: 99%) detection. Compared to standard-of-care (SOC) testing including toxin gene PCR with the following toxin antigen test, Sofia 2 demonstrates strong PPA (100%), NPA (98%), positive predictive value (71%), and negative predictive value (100%).

Sofia 2 C. difficile FIA generates rapid results that are comparable to other commercial immunoassays with a simple workflow, supporting its use for CDI diagnosis in clinical practice.

Clostridioides difficile infections (CDIs) are associated with significant morbidity, mortality, and economic burden globally. International guidelines conflict on various aspects of management, so we conducted a clinician survey to evaluate global practice variability on CDI diagnosis, treatment, and prophylaxis to inform future clinical trials.

An anonymous online survey through REDCap was distributed through multiple channels. Attending physicians, infectious disease pharmacists, and fellows in infectious diseases or medical microbiology who had managed ≥3 cases of CDI in the preceding year were eligible. Responses were compared across continents by chi-square test.

Three hundred fifty-nine survey responses were collected from 31 countries and 6 continents (North America 80.5%, Europe 11.7%, other continents 7.8%). A 2-step CDI diagnostic algorithm was used by 75.8% of respondents with heterogeneity in assay type. Similarly, there was significant variability in first-line agents for the treatment of first episodes and first recurrences of uncomplicated CDI and a lack of consensus on treatments for fulminant CDI. Secondary CDI prophylaxis during antibiotic re-exposure was most commonly used in North America (84.1%), followed by other continents (50.0%) and Europe (31.0%; P < .001). Oral vancomycin was the most frequently used agent (96.3%), with significant variability in the dose (125-500 mg daily) and duration (1-28 days; P < .01).

Substantial global variability exists with respect to CDI diagnosis, treatment, and secondary prophylaxis, likely due to divergent guidelines and a paucity of robust evidence. These findings highlight critical knowledge gaps and areas of clinical equipoise and underscore the need for further randomized controlled trials to establish harmonized international best practices for CDI.

Diarrhoeal diseases claim more than 1 million lives annually and are a leading cause of death in children younger than 5 years. Comprehensive global estimates of the diarrhoeal disease burden for specific age groups of children younger than 5 years are scarce, and the burden in children older than 5 years and in adults is also understudied. We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 to assess the burden of, and trends in, diarrhoeal diseases overall and attributable to 13 pathogens, as well as the contributions of associated risk factors, in children and adults in 204 countries and territories from 1990 to 2021.

We used the Cause of Death Ensemble modelling strategy to analyse vital registration data, verbal autopsy data, mortality surveillance data, and minimally invasive tissue sampling data. We used DisMod-MR (version 2.1), a Bayesian meta-regression tool, to analyse incidence and prevalence data identified via systematic reviews, population-based surveys, and claims and inpatient data. We calculated diarrhoeal disability-adjusted life-years (DALYs) as the sum of years of life lost (YLLs) and years lived with disability (YLDs) for each location, year, and age-sex group. For aetiology estimation, we used a counterfactual approach to quantify population-attributable fractions (PAFs). Additionally, we estimated the diarrhoeal disease burden attributable to the independent effects of risk factors using the comparative risk assessment framework.

In 2021, diarrhoeal diseases caused an estimated 1·17 million (95% uncertainty interval 0·793-1·62) deaths globally, representing a 60·3% (50·6-69·0) decrease since 1990 (2·93 million [2·31-3·73] deaths). The most pronounced decline was in children younger than 5 years, with a 79·2% (72·4-84·6) decrease in diarrhoeal deaths. Global YLLs also decreased substantially, from 186 million (147-221) in 1990 to 51·4 million (39·9-65·9) in 2021. In 2021, an estimated 59·0 million (47·2-73·2) DALYs were attributable to diarrhoeal diseases globally, with 30·9 million (23·1-42·0) of these affecting children younger than 5 years. Leading risk factors for diarrhoeal DALYs included low birthweight and short gestation in the neonatal age groups, child growth failure in children aged between 1-5 months and 2-4 years, and unsafe water and poor sanitation in older children and adults. We estimated that the removal of all evaluated diarrhoeal risk factors would reduce global DALYs from 59·0 million (47·2-73·2) to 4·99 million (1·99-10·0) among all ages combined. Globally in 2021, rotavirus was the predominant cause of diarrhoeal deaths across all ages, with a PAF of 15·2% (11·4-20·1), followed by norovirus at 10·6% (2·3-17·0) and Cryptosporidium spp at 10·2% (7·03-14·3). In children younger than 5 years, the fatal PAF of rotavirus was 35·2% (28·7-43·0), followed by Shigella spp at 24·0% (15·2-37·9) and adenovirus at 23·8% (14·8-36·3). Other pathogens with a fatal PAF greater than 10% in children younger than 5 years included Cryptosporidium spp, typical enteropathogenicEscherichia coli, and enterotoxigenic E coli producing heat-stable toxin.

The substantial decline in the global burden of diarrhoeal diseases since 1990, particularly in children younger than 5 years, supports the effectiveness of health interventions such as oral rehydration therapy, enhanced water, sanitation, and hygiene (WASH) infrastructure, and the introduction and scale-up of rotavirus vaccination. Targeted interventions and preventive measures against key risk factors and pathogens could further reduce this burden. Continued investment in the development and distribution of vaccines for leading pathogens remains crucial.

Bill & Melinda Gates Foundation.

CDBN-YGXZ shows a low minimal inhibitory concentration range from 0.015 to 0.125 mg/L against clinical Clostridioides difficile strains with diverse genotypes, hardly induces bacterial resistance, and intensively inhibits 86.2 % of C. difficile adhesion to intestinal epithelial cells Caco-2. CDBN-YGXZ shows highly antibacterial activity and is potentially a candidate as a therapeutic drug.

All currently used therapeutic protocols and drugs for Clostridioides difficile infection (CDI) treatment do not have a satisfying success and usually cost a lot.

To compare the efficacy of vancomycin monotherapy vs modified dual therapy with vancomycin + nifuroxazide as a therapeutic protocol for a medium-severe form of CDI. In addition, the effects of a modified therapeutic protocol with standard monotherapy on the number of stools and stool consistency in a medium-severe CDI will be compared.

A prospective, randomized, controlled clinical trial that included 60 patients divided into two groups was conducted. One group of patients was treated with vancomycin monotherapy. The other group was treated with the modified therapeutic protocol (vancomycin + nifuroxazide).

The modified therapy with vancomycin + nifuroxazide demonstrated enhanced pharmacological efficacy in the management of CDI compared to the standard vancomycin monotherapy. Patients treated with dual therapy reported a significantly lower number of stools in first, second and third control; first control (4.47 ± 2.20 compared to 5.70 ± 1.91 in vancomycin group (p = 0.024)), second control (2.37 ± 0.85 compared to 3.13 ± 0.90 in vancomycin group (p = 0.001)), and third control (1.53 ± 0.51 compared to 1.80 ± 0.61 in vancomycin group (p = 0.035)). Also, the first and third controls noted significant improvements in stool consistency, measured as a decrease in the number of completely watery stools (p = 0.011 and p < 0.001, respectively).

Nifuroxazide and vancomycin have demonstrated accelerated improvement in patient status and hold promise as a novel dual therapeutic regimen for managing patients diagnosed with a medium-severe form of CDI.

Ibezapolstat (IBZ) is a competitive inhibitor of the bacterial Pol IIIC enzyme in clinical development for the treatment of Clostridioides difficile infection (CDI). Previous studies demonstrated that IBZ carries a favorable microbiome diversity profile compared to vancomycin (VAN). However, head-to-head comparisons with other CDI antibiotics have not been done. The purpose of this study was to compare microbiome changes associated with IBZ to other clinically used CDI antibiotics. Groups of germ-free (GF) mice received a fecal microbiota transplant from one of two healthy human donors and were subsequently exposed to either IBZ, VAN, fidaxomicin (FDX), metronidazole (MET), or no antibiotic (control). 16S rRNA encoding gene sequencing of temporally collected stool samples was used to compare the gut microbiome perturbations between treatment and no-drug control groups. Among the tested antibiotics, the most significant change in microbiome diversity was observed in MET-treated mice. Each antibiotic had a unique effect, but changes in alpha and beta diversities following FDX- and IBZ-treated groups were less pronounced than those observed in VAN- or MET-treated groups. By the end of therapy, both IBZ and FDZ increased the relative abundance of Bacteroidota (phylum), with IBZ additionally increasing the relative abundance of Actinomycetota (phylum). In microbiome-humanized mice, IBZ and FDX had smaller effects on gut microbiome diversity than VAN and MET. Notable differences were observed between the microbiome of IBZ- and FDX-treated groups, which may allow for differentiation of these two antibiotics in future studies.

Clostridioides difficile infection (CDI) is a well-recognized complication of inflammatory bowel disease (IBD) that has been associated with poor clinical outcomes. The objective of this study is to characterize the global incidence, risk factors and outcomes of CDI in patients with IBD.

A search of MEDLINE/PubMed, Scopus, and Cochrane Database of Systematic Reviews was conducted for studies published between January 1960, and March 2024. Random-effect models were employed to estimate the incidence of CDI in the IBD population. Risk factors and outcomes were estimated using random effects meta-regression and subgroup analysis.

Twenty-eight articles from 11 countries on 3 continents, comprising 796, 244 patients with IBD were included. The overall CDI rate was 8.84% (95% CI, 5.91%-13.03%). The rate of CDI was slightly higher in Asia at 11% (95% CI, 6.7%-18.44%) compared to the North America (USA and Canada) at 7.85% (95% CI, 3.80%-15.51%) and Europe, where the incidence, was 7.92% (95% CI, 3.87%-15.51%). A univariable random-effects meta-regression model demonstrated that male gender (odds ratio [OR], 1.18; 95% CI, 1.00-1.40) and older age (OR, 1.06; 95% CI, 0.99-1.15, per one-year increase in age) were factors associated with higher CDI incidence in the IBD population. CDI testing by PCR compared to enzyme immunoassay was associated with higher rates of CDI (OR, 4.70; 95% CI, 01.39-15.90). No association was observed between length of hospital stay and CDI.

One in 10 patients with IBD were positive for CDI. Increasing age and male population were associated with higher risk of CDI.

Clostridioides difficile (formerly known as Clostridium difficile) is a significant cause of healthcare-associated infection with symptoms ranging from diarrhoea and abdominal pain to pseudomembranous colitis and toxic megacolon. Severe disease can pose a significant morbidity and mortality risk and is to be considered a medical emergency. The emergence of a new C. difficile ribotype with an estimated mortality rate of 20% (ribotype 995) has prompted a re-review of the evidence and guidelines around managing severe C. difficile infections (CDI). International guidance on the management of CDI varies regarding first-line antibiotic choice. Metronidazole is no longer favoured as first line due to concerns around resistance, and vancomycin and fidaxomicin are now recommended as first line options. Antibiotic therapy should be used in conjunction with good supportive measures and early consideration of surgical management. Faecal microbiota transplant can be utilized in recurrent CDI and may be useful in severe disease. Severe CDI is a significant ongoing threat to public health, and further research into effective management is essential to ensure the best possible outcomes for patients.

Clostridioides difficile (C. difficile) infection (CDI) is common after antibiotic exposure and presents significant morbidity, mortality and healthcare costs worldwide. The rising incidence of recurrent CDI, driven by hypervirulent strains, widespread antibiotic use and increased community transmission, has led to an urgent need for novel therapeutic strategies. Conventional antibiotic treatments, although effective, face limitations due to rising antibiotic resistance and high recurrence rates, which can reach up to 60% after multiple infections. This has prompted exploration of alternative therapies such as fecal microbiota-based therapies, including fecal microbiota transplantation (FMT) and live biotherapeutics (LBPs), which demonstrate superior efficacy in preventing recurrence. They are aimed at restoring the gut microbiota. Fecal microbiota, live-jslm and fecal microbiota spores, live-brpk have been approved by the U.S. Food and Drug Administration in individuals aged 18 years or older for recurrent CDI after standard antimicrobial treatment. They have demonstrated high efficacy and a favorable safety profile in clinical trials. Another LBP under study includes VE-303, which is not derived from human donor stool. This review provides a comprehensive overview of the current therapeutic landscape for CDI, including its epidemiology, pathophysiology, risk factors, diagnostic modalities and treatment strategies. The review delves into the emerging role of live biotherapeutics, with a particular focus on fecal microbiota-based therapies. We explore their development, mechanisms of action, clinical applications and potential to revolutionize CDI management.

Recurrent Clostridioides difficile infection (rCDI) is common, with symptoms ranging from diarrhea to life-threatening sepsis. This study aimed to assess the real-world outcomes of patients with rCDI in the United States (US) who received fecal microbiota, live-jslm (RBL), the first US Food and Drug Administration-approved microbiota-based therapy for the prevention of rCDI after antibiotic treatment.

Adults with rCDI who received RBL between July 2023 and August 2024 at home or in a clinic and had ≥ 8 weeks of follow-up or experienced CDI recurrence at any time after RBL administration were included. Treatment success, defined as no CDI recurrence within 8 weeks of RBL, was assessed overall and in subgroups stratified by age, number of prior CDI recurrences, duration of the antibiotic washout period, prior bezlotoxumab use, and RBL administration setting.

Among 196 patients who received RBL, 176 had either ≥ 8 weeks of follow-up or had < 8 weeks of follow-up but experienced CDI recurrence during that period. The treatment success rate at 8 weeks was 83.0%. No significant differences were observed in treatment success rates among subgroups based on age (< 65 years old vs. ≥ 65 years old: 85.9% vs. 80.2%, p = 0.20), duration of the antibiotic washout period (24 h: 80.0%, 48 h: 84.5%, 72 h: 85.0%, p = 0.68), number of prior CDI recurrences (< 3 vs. ≥ 3: 82.5% vs. 83.1%, p = 0.60), or prior bezlotoxumab use (86.4% vs. 83.7%, p = 1.00). Patients receiving RBL at home had a higher treatment success rate compared to those receiving RBL in a clinic (87.3% vs. 62.5%, p < 0.01).

RBL was highly effective in preventing rCDI in a real-world setting, including at-home administration. The effectiveness was also observed among high-risk subgroups, such as patients ≥ 65 years old and those with ≥ 3 prior CDI recurrences.

Introduction Infectious diarrhea represents a significant and frequent complication among kidney transplant recipients, primarily due to the immunosuppressive therapy required to prevent graft rejection. This condition poses substantial risks to both graft function and patient survival, driven by increased susceptibility to opportunistic pathogens and potential medication-related gastrointestinal effects. This study aims to characterize the pathogen spectrum and associated risk factors of infectious diarrhea in a German cohort of kidney transplant recipients, providing insights into regional patterns and clinical implications. Methods A retrospective cohort study was conducted, analyzing 604 patients, including 436 kidney transplant recipients, who were hospitalized with infectious diarrhea (ICD-10 codes A00-A09) at the Universitätsklinikum Düsseldorf (UKD) between January 2019 and December 2023. Nontransplant patients (n = 168) were included as a comparison group to evaluate pathogen distribution and infection risk specific to immunosuppressive therapy in transplant recipients. Pathogen identification was performed focusing on stool samples. Data collected included transplantation status, dates of admission and transplantation, recurrence rates, and detailed immunosuppressive regimens. Statistical analyses were applied to evaluate pathogen distribution, temporal patterns, and the influence of immunosuppression on infection risk. Results The most prevalent pathogens identified among kidney transplant recipients were Clostridioides difficile (26.3%), cytomegalovirus (CMV, 12.3%), enteropathogenic Escherichia coli (EPEC, 8.6%), and norovirus (4.8%). Immunosuppression significantly heightened infection susceptibility, with Clostridioides difficile infections occurring notably more frequently and CMV-related diarrhea observed exclusively in the transplant cohort. Recurrence rates were elevated for both CMV and Clostridioides difficile, underscoring their clinical persistence. Temporal analysis revealed a median onset of CMV infections at approximately 13 months post-transplantation, with no significant seasonal variation. Conclusions The predominance of opportunistic pathogens such as Clostridioides difficile and CMV in kidney transplant recipients reflects the profound impact of immunosuppression on infection risk and pathogen profiles. These findings emphasize the necessity for enhanced diagnostic approaches in kidney transplant recipients, including early and comprehensive pathogen screening, and targeted prevention strategies, such as optimized and maybe prolonged CMV prophylaxis and stringent hygiene protocols for Clostridioides difficile. It emphasizes close monitoring of a potential viral load in blood samples, especially after cessation of the routine CMV prophylaxis after kidney transplantation. This study contributes to a better understanding of infectious diarrhea in this vulnerable population and lays the groundwork for improved clinical management, overall cost reduction, and future prospective research.

We aimed to describe the characteristics of Clostridioides difficile infection (CDI) in cancer patients, analysing risk factors for 90-day recurrence and attributable mortality.

Retrospective analysis on all CDI episodes from 2020 to 2022 in three Australian hospitals and one Spanish hospital. Logistic regression analyses were performed.

A total of 547 CDI episodes in cancer patients were documented. Treatment predominantly involved vancomycin (81.5%), followed by metronidazole (15.0%) and fidaxomicin (9.1%). Combined antibiotics were used in 61 (11.2%) episodes. The 90-day recurrence rate was 15.6%. Independent risk factors for CDI recurrence were female sex (OR 2.26, 95% CI 1.13-4.52), age >75 years (OR 2.69, 95% CI 1.30-5.59), dialysis (OR 5.15, 95% CI 1.45-18.27), vomiting at presentation (OR 0.06, 95% CI 0.01-0.55), colonic wall thickening in the CT abdomen (OR 2.42, 95% CI 1.06-5.49) and vancomycin therapy (OR 4.60, 95% CI 1.34-15.84). Overall, 90-day mortality was 22.3%, but attributable mortality was 4.9%. Risk factors for mortality attributed to CDI were age >65 years (OR 15.91, 95% CI 2.64-95.80), previous cerebrovascular disease (OR 20.27, 95% CI 3.12-131.84), antibiotic therapy within the last 30 days (OR 0.17, 95% CI 0.05-0.54), high-output diarrhoea (OR 6.68, 95% CI 1.68-26.56), high CRP-levels (OR 11.60, 95% CI 1.90-70.81) and need for treatment change (OR 6.65, 95% CI 2.20-20.08).

CDI recurrence rates among cancer patients remain significant. Nonetheless, fidaxomicin and other preventive strategies are seldom used. We identified several factors that could inform the implementation of these strategies in cancer patients.

Background: Exposure to antimicrobials and Proton Pump Inhibitors (PPIs) are modifiable risk factors for nosocomial Clostridiodes difficile infection (CDI). We investigated the association between these agents and nosocomial CDI over five years. Methods: Nosocomial CDI from January 2017 to December 2021 were included. Consumption trends were analyzed using a simple linear regression model. A correlation analysis was performed using Spearman's test in two ways: without a time interval and with 1-month interval matching. An interrupted time-series method to evaluate the impact of three key temporal breakpoints on CDI incidence rate was performed using the Poisson regression model. Results: A downward trend for cephalexin, ceftriaxone, clindamycin, gentamicin, macrolides, metronidazole, and penicillin sodium was identified. In contrast, an upward trend was recognized for amoxicillin, ceftazidime/avibactam, ertapenem, fluconazole, ketoconazole, levofloxacin, and tigecycline. Among the antimicrobials that showed a positive association between consumption and the incidence of CDI are clindamycin and cephalosporins after immediate consumption. Moreover, macrolides and metronidazole presented a positive correlation, in both immediate and delayed consumption. PPIs consumption did not show changes and was not associated with nosocomial CDI incidence. The interrupted time series analysis showed no changes at the breakpoints selected. Conclusions: Consumption of clindamycin, cephalosporins, and macrolides showed positive association with CDI, despite having a downtrend in consumption. Specific events, such as the COVID-19 pandemic and the implementation of ASP, have had no correlation with CDI. Further analysis is required in Latin America to advance our understanding of risk factors associated with CDI.

This study investigated the safety, reactogenicity, and immunogenicity in healthy subjects of a Clostridioides difficile vaccine candidate with/without adjuvant, targeting toxins A and B.

In this first-in-human, phase 1, observer-blind study, subjects aged 18-45 years were randomized to receive F2 antigen (n = 10) or placebo (n = 10), and subjects aged 50-70 years to receive F2 antigen plus AS01 adjuvant (n = 45), F2 antigen (n = 45), or placebo (n = 30) in 2 doses 1 month apart. A subcohort (n = 40) received a third dose 15 months later. Solicited adverse events (AEs) were recorded for 7 days and unsolicited AEs for 30 days after each dose. Immunogenicity was assessed at baseline and after each dose.

Solicited AEs were transient and most frequent in subjects receiving F2 antigen plus AS01. No serious AEs were considered related to study vaccine. Immunogenicity was substantially higher in subjects receiving F2 antigen plus AS01 than subjects receiving F2 antigen alone. A third dose increased the immune response in subjects with baseline neutralization titers below the assay lower limit of quantitation.

The GSK C. difficile vaccine candidate was immunogenic, especially when given with AS01, and was well tolerated with an acceptable safety profile.

NCT04026009.

Clostridium difficile infection (CDI), characterized by diarrheal illness with serious complications, is a common pathology in clinical practice. We present a series of five patients with CDI who underwent treatment with fidaxomicin following the failure of oral vancomycin. To our knowledge, no evidence in the literature suggests that fidaxomicin is more effective than vancomycin in treating acute infection. This paper emphasizes the importance of utilizing a large study to determine the relative effectiveness of vancomycin versus fidaxomicin in treating CDI. We also provide a literature review on CDI and management evolution.

Clostridioides difficile is a major burden for both healthcare systems and the patients. Faecal microbiota transplantation (FMT) is becoming more common as a treatment since it reduces the risk of recurrent Clostridioides difficile infection (rCDI).

To evaluate how treatment with FMT is affecting the health-related quality of life (HRQoL) in patients with rCDI.

A prospective observational cohort study was conducted where patients who were offered FMT as a treatment for rCDI were asked to fill in a questionnaire based on the Short Health Scale (SHS) and EuroQol 5-Dimensions 5-Levels (EQ-5D-5L) about their HRQoL before and after treatment.

Patients with rCDI had poor HRQoL, which improved following FMT.

Since FMT cures, reduces the risk of new recurrences of CDI and improves the HRQoL of the patients, it should be offered as a treatment for patients with rCDI. Also, SHS is a useful and reliable instrument for measuring HRQoL in patients with rCDI.

Clostridioides difficile infection (CDI) is associated with significant morbidity and mortality within the Australian population. Treatment recommendations for CDI pose challenges at both community and hospital-based levels due to the recurrent, refractory and potentially severe nature of the disease. Since the last published Australasian guidelines in 2016, new therapeutic options are available, prompting a necessary update to management recommendations. On behalf of the Australasian Society of Infectious Diseases, we present the updated guidelines for the management of CDI in adults and children exploring the changes to treatment recommendations - including the replacement of oral metronidazole with vancomycin for initial CDI and the emerging role for fidaxomicin and faecal-microbiota transplant.

Recurrent Clostridioides difficile infection (CDI) is primarily driven by antibiotic-induced disruption of the indigenous intestinal microbiota. Restoration of microbiota through fecal microbiota transplantation (FMT) is effective in preventing subsequent CDI, although this effect is attenuated with additional antibiotic exposure. The aim of this study was to identify the risk factors for recurrent antibiotic administration after FMT.

This is a prospective cohort of patients who were administered FMT for recurrent CDI from 1 July 2019 through 23 November 2023 across 6 institutions in the United States. Providers collected de-identified data at the time of FMT administration and in the months post-FMT administration.

The analysis included 448 patients. Risk factors for non-CDI antibiotic administration within 2 months of FMT included immunocompromised status (odds ratio [OR], 2.2 [95% confidence interval {CI}, 1.1-4.4]; P = .02), >3 non-CDI antibiotic courses pre-FMT (OR, 3.1 [95% CI, 1.4-6.8]; P = .006), and prior hospitalization for CDI (OR, 2.0 [95% CI, 1.1-3.8]; P = .02). The most common indications for non-CDI antibiotic administration post-FMT were urinary tract infections, respiratory infections, and procedure prophylaxis.

Non-CDI antibiotic exposure significantly increases the risk of CDI recurrence post-FMT. Risk factors for non-CDI antibiotic administration within 2 months of FMT include immunocompromised status, multiple prior non-CDI antibiotics, and prior hospitalization for CDI. These individuals may benefit from additional or modified recurrent CDI prevention strategies.

Clostridioides difficile (C. difficile) remains the leading cause of healthcare-associated diarrhoea, posing treatment challenges because of antibiotic resistance and high relapse rates. Faecal microbiota transplantation is a novel treatment strategy to prevent relapses of C. difficile infection (CDI), however, the exact components conferring colonization resistance are unknown, hampering its translation to a medicinal product. The development of novel products independent of antibiotics, which increase colonization resistance or induce protective immune mechanisms is urgently needed.

To establish a framework for a Controlled Human Infection Model (CHIM) of C. difficile, in which healthy volunteers are exposed to toxigenic C. difficile spores, offering the possibility to test novel approaches and identify microbiota and immunological targets. Whereas experimental exposure to non-toxigenic C. difficile has been done before, a toxigenic C. difficile CHIM faces ethical, scientific, logistical, and biosafety challenges.

Specific challenges in developing a C. difficile CHIM were discussed by a group of international experts during a workshop organized by Inno4Vac, an Innovative Health Initiative-funded consortium.

The experts agreed that the main challenges are: developing a clinically relevant CHIM that induces mild to moderate CDI symptoms but not severe CDI, determining the optimal C. difficile inoculum dose, and understanding the timing and duration of antibiotic pretreatment in inducing susceptibility to CDI in healthy volunteers.

Should these challenges be tackled, a C. difficile CHIM will not only provide a way forward for the testing of novel products but also offer a framework for a better understanding of the pathophysiology, pathogenesis, and immunology of C. difficile colonization and infection.

The diagnosis, pharmacologic management, and surgical options for Clostridioides difficile infection (CDI) are rapidly evolving, which presents a challenge for the busy surgeon to remain up to date on the latest clinical guidelines. This review provides an evidence-based practical guide for CDI management tailored to the needs of surgeons and surgical intensivists. Historically, the diagnosis of CDI relied on slow cell culture cytotoxicity neutralization assays, but now, the rapidly resulting nucleic acid amplification tests and enzyme immunoassays have become mainstream. In terms of antibiotic therapy, metronidazole and oral vancomycin were the main "workhorse" antibiotics in the early 2000s, but large randomized controlled trials have now demonstrated that fidaxomicin produces superior results. Regarding surgical intervention, total abdominal colectomy was once the only procedure of choice; however, diverting loop ileostomy with colonic lavage is emerging as a viable alternative. Finally, novel adjuncts such as fecal microbiota transplantation and targeted therapy against toxin B (bezlotoxumab) are playing an increasingly important role in the management of CDI.

Clostridioides difficile infections are difficult and serious problem occurring in patients staying in intensive care units. In recent years, the number and severity of these infections, as well as the mortality rate, have been increasing, posing a serious epidemiological problem. This is caused, among other factors, by stressors, artificial nutrition, and sepsis, which lead to disturbances in the patients' microbiome. Basic method of treatment is antibiotic therapy, however some patients experience recurrences of the infection. Fecal Microbiota Transplantation (FMT) is one of the alternative methods used in treating recurring infections of Clostridioides difficile etiology (Clostridioides Difficile Infection, CDI). The presented case refers to a patient with severe pseudomembranous enterocolitis who underwent FMT twice. This report highlights the role of FMT in the treatment of severe Clostridioides difficile infections in critically ill patients.

Background/Objectives:Clostridioides difficile infection (CDI) poses a significant healthcare challenge, with recurrence rates reaching 30%, leading to substantial morbidity and costs. Fidaxomicin (FDX) and bezlotoxumab (BEZ) have shown potential in reducing recurrence; however, real-world data on the efficacy of their combination in high-risk CDI patients remain limited. This study aimed to evaluate the efficacy and safety of FDX + BEZ compared with FDX alone in CDI patients with recurrence risk factors. Methods: CDI patients with ≥two recurrence risk factors treated with FDX alone or FDX + BEZ were analyzed. Sixteen factors were evaluated as risk factors for recurrent CDI based on findings from previous studies. Patients with FDX treatment duration <10 days or other CDI treatment prior to FDX were excluded. Outcomes included recurrence within 2 months, global and clinical cure rates, and adverse events. Univariate and multivariate analyses were performed to evaluate efficacy. Results: Among 82 patients, the FDX + BEZ group (n = 30) demonstrated significantly higher global (86.7% vs. 65.4%; p < 0.05) and clinical cure rates (90.0% vs. 69.2%; p < 0.05) compared with the FDX-alone group (n = 52), despite more severe cases in the combination group. Recurrence rates were non-significantly lower in the FDX + BEZ group (3.3% vs. 11.5%). Combination therapy also accelerated diarrhea resolution without additional adverse events. Multivariate analysis identified FDX + BEZ as significantly associated with improved clinical cure (adjusted odds ratio 4.167; 95% CI: 1.029-16.885). Conclusions: FDX + BEZ therapy offers superior efficacy and safety in CDI patients with recurrence risk factors, presenting a promising strategy for optimizing CDI management.

A review of the diagnostic and therapeutic management algorithm of the pathogen Clostridioides difficile for daily practice is presented. Its diagnosis, in any unformed stool sample sent to the laboratory, is based on a two-step algorithm, with demonstration of the pathogen by means of its enzyme glutamate dehydrogenase by immunoassay and subsequent PCR (polymerase chain reaction) of its toxin. The mainstay of step therapy, reserved for symptomatic patients, is fidaxomicin, over vancomycin. Metronidazole is not an adequate treatment. Emerging therapies, such as faecal microbiota transplantation or the antibody bezlotoxumab, are gaining importance in patients with risk factors or relapses. Surgery is indicated in patients with worse prognosis and complications. Prevention is essential, based on vigilance and contact precautions, in addition to the elimination of spores from the environment.

Diarrhea, as the well-known clinical feature of Clostridioides difficile infection (CDI), may be absent at the initial presentation, leading to delays in diagnosis. The delay is due to both underrecognition of such presentations and the dependence of CDI diagnosis on stool samples. This review was conducted to evaluate the literature for CDI cases presenting without diarrhea, raise awareness about the possibility of CDI in the differential diagnosis regardless of diarrhea, and assemble relevant data to harmonize clinical approaches. The PubMED Medline database was used to conduct this literature review, focusing on reported CDI cases presenting without diarrhea. After exclusions, 22 articles were included for analysis, providing data for 48 cases. This paper will present the selected clinical data of these 48 patients and follow a real-life case with a clinical course of CDI including presentation, diagnosis, management, and outcomes. The excessive mortality and bowel resection rates of CDI patients presenting without diarrhea were the notable findings. Poor prognosis was possibly inflated by delayed diagnoses in an unfamiliar setting, emphasizing the importance of a high index of suspicion to allow early recognition of CDIs in the appropriate clinical context despite the absence of diarrhea.

The primary purposes of this review are to provide a brief overview of the microbiome, discuss the most relevant outcome data and key characteristics of each live microbiome agent, and pose questions for consideration going forward as these agents are integrated into clinical practice.

The management of Clostridiodes difficile infection (CDI) remains a difficult clinical conundrum, with recurrent CDI occurring in 15% to 35% of patients and causing significant morbidity and decreased quality of life. For patients with frequent CDI recurrences, fecal microbiota transplantation (FMT) has been demonstrated to have significant benefit but also significant risks, and FMT is not approved by the US Food and Drug Administration (FDA) for that indication. FDA has established a new therapeutic class for agents known as live biotherapeutic products (LBPs) that offer significant advantages over FMT, including standardized screening, testing, and manufacturing as well as known quantities of organisms contained within. Two new live microbiome products within this class were recently approved by FDA for prevention of CDI recurrences in adult patients following treatment for recurrent CDI with standard antimicrobial therapy. Both agents had demonstrated efficacy in registry trials in preventing CDI recurrence but differ significantly in a number of characteristics, such as route of administration. Cost as well as logistics are current obstacles to use of these therapies.

Live microbiome therapy is a promising solution for patients with recurrent CDI. Future studies should provide further evidence within yet-to-be-evaluated populations not included in registry studies. This along with real-world evidence will inform future use and clinical guideline placement.

Clostridioides difficile infection (CDI) in inflammatory bowel disease (IBD) has been associated with poor clinical outcomes. The relationship between biologic therapy and CDI is controversial. We aimed to assess whether biologic therapy increases CDI risk among IBD patients, to identify factors associated with increased CDI risk, and to characterize CDI episodes in our population.

We included patients diagnosed with IBD (IBD-cohort) and immune-mediated inflammatory rheumatic diseases (Rheuma-cohort). Risk factors for CDI were assessed using a logistic regression model. We also estimated the incidence rate of CDI for each biologic.

We included 1866 patients: 1041 from the IBD-cohort and 825 from the Rheuma-cohort. The diagnosis of IBD was the major risk factor for developing CDI in the overall population (OR: 18.29, CI 95%: 5.59-59.80, p < 0.001). Within the IBD-cohort, patients with ulcerative colitis had an increased risk for CDI compared to Crohn's disease (OR:2.00, 95% CI: 1.18-3.42, p = 0.011). Although the subgroup of IBD patients receiving biologics showed a higher incidence of CDI compared to unexposed IBD patients, biologic therapy was not an independent risk factor for CDI in the logistic regression model; nevertheless, patients who received 3 or more biologic agents had a significantly higher risk for CDI (OR: 3.09, CI 95% 1.13-8.47, p = 0.028).

IBD significantly increases the risk of CDI among patients treated with biologic therapy; although such treatments do not seem to individually increase the risk, the number of biologics received may be a new predictor of CDI.

Diarrhea is a common complication after pediatric kidney transplantation. While mycophenolate mofetil is an important and common cause of post-transplant diarrhea, diarrhea can result from infectious and other non-infectious causes. Many complications can result from severe diarrhea including acute kidney injury from dehydration. Other unique complications in transplant recipients include tacrolimus toxicity and acute rejection (from changes in immunosuppressive pharmacokinetics or dosing in response to the diarrhea). Therefore, a thorough evaluation is recommended for all pediatric patients with severe diarrhea to ensure that appropriate interventions are instituted, and risks of complications minimized. Our review describes the scope of the morbidity of diarrheal illness after transplantation, common causes, and newer insights in the management of diarrhea, both supportive and targeted to the underlying cause.

Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated diarrhea, with substantial morbidity and mortality. CDI is a severe and growing problem with numerous treatment options. We evaluated the effectiveness of all therapies in recurrent and non-recurrent infections and their prevention.

This network meta-analysis and systematic review of randomized controlled trials (RCTs) compared all CDI therapies and preventions. We included RCTs published until 19 August 2024 and focused on adult population. We performed a systematic search in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials. Inclusion criteria were patients: adults (>16) treated against CDI; study type: randomized controlled trial; outcome: cure rate, recurrence or effectiveness of prevention. Any publication not meeting all criteria was considered to be ineligible and excluded. We applied random-effects meta-analysis using frequentist methods. We reported our main results as odds ratios (as a symmetric effect size measure, OR) with 95% confidence interval (95% CI). We used the Cochrane risk-of-bias tool to assess the risk of bias. Our study protocol was preregistered in PROSPERO (CRD42022371210).

We assessed 73 RCTs with 28 interventions, involving 27,959 patients (49.2% female) in five networks. Fecal microbiota transplantation (FMT) was the most effective treatment in terms of the cure rate overall (P-score: 0.9952) and in recurrent cases (P-score: 0.9836). In recurrent cases, fidaxomicin (P-score: 0.6734) showed significantly greater effectiveness than vancomycin (P-score: 0.3677) and tolevamer (P-score: 0.0365). For non-recurrent CDI treatments ridinilazole, fidaxomicin, FMT and nitazoxanide were equally effective. Ridinilazole (P-score: 0.7671) and fidaxomicin (P-score: 0.7627) emerged as the most effective in preventing recurrence. Probiotics were not effective in preventing CDI, since network meta-analyses did not show significant differences between probiotics and placebo. In probiotics' subgroups pairwise meta-analyses Lactobacillaceae proved to be significantly more effective in prevention than placebo. Oral and colonoscopic FMT administration methods were equally effective. The study-level aggregated risk of bias of the publications included ranged from low to high. We observed relevant heterogeneity among studies in therapeutic doses, treatment durations, and follow-up times.

The superiority of FMT in the treatment of CDI highlights the potential for increased use of FMT in clinical settings. Further research on optimizing FMT protocols and exploring its long-term safety and efficacy in larger samples is needed. Our findings suggest that the preventive use of probiotics might be questioned.

None.

The laboratory diagnosis of Clostridioides difficile infection (CDI) is controversial. Nucleic acid amplification tests (NAAT) and toxin enzyme immunoassays (EIA) are most widely used, often in combination. However, the interpretation of a positive NAAT and negative toxin immunoassay (NAAT+/EIA-) is uncertain. PubMed and EMBASE were searched for studies reporting clinical outcomes in NAAT+/EIA- versus NAAT+/EIA+ patients. Forty-six studies comprising 33,959 patients were included in this meta-analysis. All-cause mortality (RR 0.96, 95% CI 0.80-1.15), attributable mortality (RR 0.61, 95% CI 0.20-1.91), fulminant CDI (RR 0.83, 95% CI 0.57-1.20), radiographic evidence of CDI (RR 0.87, 95% CI 0.65-1.16), total CDI complications (RR 0.95, 95% CI 0.59-1.53), colectomies (RR 0.78, 95% CI 0.34-1.79), and ICU admission (RR 1.04, 95% CI 0.84-1.30) did not significantly differ between NAAT+/EIA- and NAAT+/EIA+ patients. However, rates of recurrent (RR 0.62, 95% CI 0.50-0.77) or severe (RR 0.74, 95% CI 0.63-0.88) CDI were significantly lower in NAAT+/EIA- patients than in NAAT+/EIA+ patients. The pooled prevalence of NAAT+/EIA- patients who were treated with antibiotics for CDI was 73.4% (pooled proportion 0.72, 95% CI 0.52-0.88). NAAT+/EIA- patients have lower rates of recurrence and are at reduced risk for severe CDI compared with NAAT+/EIA+ patients but have a risk of CDI-related complications and mortality comparable to that of NAAT+/EIA+ patients. Toxin results cannot rule in or rule out CDI, and the decision whether to treat symptomatic NAAT+/EIA- patients for CDI should be based on clinical presentation and not on the toxin result.IMPORTANCEClostridioides difficile infection (CDI) is a common cause of healthcare-associated infections and the leading cause of antibiotic-associated diarrhea. However, the laboratory diagnosis of CDI, primarily done by nucleic acid amplification test (NAAT) and enzyme immunoassay (EIA), is controversial, especially in patients who test positive by NAAT but negative by EIA. In this systematic review, we compared the clinical outcomes of NAAT+/EIA- versus NAAT+/EIA+ patients and found that the two groups have similar risk of mortality and CDI-related complications. However, NAAT+/EIA- patients had significantly lower rates of recurrence and severe CDI than NAAT+/EIA+ patients, and most NAAT+/EIA- patients received CDI therapy. Toxin testing can help to predict the likelihood of CDI recurrence or severe infection, but the toxin result should not be a determining factor in the administration of CDI therapy. The decision on whether to treat NAAT+/EIA- patients should be based on clinical assessment.

This retrospective cohort study evaluated the proportion of inpatients initiated and successfully discharged on fidaxomicin for Clostridioides difficile infection. Nearly, all patients (96.4%; 27/28) were able to obtain fidaxomicin to complete their treatment course, although there was variability in copays among patients with Medicare.

Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated infections worldwide, with hypervirulent strains linked to severe disease and higher mortality. This study aims to analyze the epidemiology of CDI at a tertiary-care hospital in Italy and compare clinical outcomes between patients infected with hypervirulent and non-hypervirulent strains.

A retrospective comparative study was conducted on patients diagnosed with CDI at ASST Spedali Civili di Brescia, Italy, from January 2015 to June 2023. Hypervirulent strains were identified using the GeneXpert assay as positive for cytotoxin gene (tcdB), binary toxin genes (tcdA and tcdB) and a single nucleotide deletion at position 117 in the tcdC gene and compared to a randomized matched control group with non-hypervirulent CDI. Clinical data were collected and analyzed, with multivariate logistic regression employed to identify risk factors for hypervirulent CDI.

Of 1,059 positive C. difficile specimens, a statistically significant trend between January 2015 to June 2023 was found in the increasing incidence of CDI cases per 1,000 hospital admissions and 10,000 bed-days. Notably, a remarkable increase of hypervirulent strains was recorded in 2021 and 2022 when compared to previous years. A total of 130 patients were analyzed: 62 (47.7%) with hypervirulent CDI and 68 (52.3%) controls. Hypervirulent CDI was associated with higher 30-day mortality (18% vs. 5.8%, p = 0.03). Multivariate analysis showed that hypervirulent CDI significantly increased 30-day mortality risk (OR = 9.915, CI = 2.37-61.05, p = 0.005) and that prior antibiotic therapy was a significant risk factor (OR = 5.49, CI = 1.19-39.96, p = 0.047).

Our epidemiological data, while suggesting a potential resurgence in CDI transmission during COVID-19 pandemic, are derived from a single-center experience with limited generalizability to the broader population. Nonetheless, they highlight the need for strengthened antimicrobial stewardship and national surveillance systems to effectively monitor and manage these strains.

Objective The objective of this study is to investigate the predisposing factors, disease course, potential complications, role of primary prophylaxis, and overall clinical outcomes of Clostridioides difficile infection (CDI) in cancer patients. Methods The study was conducted at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan. We analyzed the medical records of cancer patients diagnosed with CDI from July 2015 to July 2024 and collected data about demographic characteristics, clinical presentation, predisposing factors, treatment, complications, and mortality rates. We used SPSS version 25 (IBM Corp., Armonk, NY) for data analysis. Results Out of 61 patients, 55.7% (n=34) were men, and most of the patients belonged to the age group of 41-65 years (49.1%; n=30). Of the patients, 34.4% (n=21) had underlying hematological malignancy, while the majority of patients (63.9%; n=39) had underlying solid organ malignancy. A total of 45.9% (n=28) of patients had mild severity, whereas 16.3% (n=10) and 6.55% (n=4) were at severe and fulminant stages of CDI, respectively. The creatinine levels of 80.3% (n=49) of patients were less than 1.5 mg/dL. We also observed the prior antimicrobial use, previous hospitalization within the last four weeks, recent chemotherapy, and use of proton pump inhibitors (PPIs)/H2 antagonists in the past four weeks as predisposing factors in 78.6% (n=48), 72.1% (n=44), 55.7% (n=34), and 75.4% (n=46) of patients, respectively. A greater proportion of patients (68.8%; n=42) had hospital/ICU stays of less than 15 days. Of the patients, 29.6% (n=18) had comorbid conditions such as diabetes mellitus (DM), chronic kidney disease (CKD), hypertension (HTN), ischemic heart disease (IHD), hepatitis, and atrial fibrillation. Oral vancomycin was administered as the primary treatment in 78.6% (n=48) of patients. We noted the resolution of symptoms in 91.8% (n=56) of patients, while 83.6% (n=51) of patients developed no complications. Additionally, the radiological findings of the patients were negative for toxic megacolon. Moreover, 4.91% (n=3) of patients had recurrent infections, whereas all-cause 30-day mortality was 13.1% (n=8). The mortality rate was higher in patients with solid organ tumors (17.9%; n=7) as compared to those having hematological malignancy (4.76%; n=1). Regression analysis showed that recent chemotherapy had an odds ratio (OR) of 11.550 (95% confidence interval {CI}: 1.332-100.9; p=0.998). Conclusion Cancer patients, especially those with solid tumors presenting with symptoms suggestive of CDI and prior chemotherapy exposure, need careful evaluation and preemptive treatment as CDI-related mortality is higher in cancer patients. Early diagnosis and treatment in this population can be lifesaving. Moreover, all cancer patients should receive CDI prophylaxis when indicated.

Clostridioides difficile (CDI) is a common cause of infectious diarrhea. The current recommendation is to initiate empirical antibiotic treatment for suspected CDI who have an anticipated delay of confirmatory results or fulminant colitis. This is based on limited clinical trials. The study aims to examine the impact of early treatment on mortality and clinical outcomes.

This retrospective cohort study included adult patients with CDI. Early treatment was defined as the initiation of an anti-Clostridioides medication within the first 24 h following stool sampling. Outcomes were 30 and 90 day mortality, length of hospital stay (LOS), recurrence, and colectomy rate. To address potential bias, propensity score matching followed by logistic regression was performed, P value less than 5% was considered statistically significant.

Study cohort consisted of 796 patients; clinical characteristics were balanced following matching. There was no difference, in favor of early treatment, between the groups regarding 30 day mortality and 90 day mortality with HR of 0.91 (95% CI 0.56-1.47) and 0.7 (95% CI 0.45-1.08), respectively. No statistically significant difference in recurrence rate, ICU admission or colectomy rate was observed. The LOS was shorter in the early-treatment group with 6 days vs. 8 days.

Early treatment for CDI had shortened hospital stay. However, it did not affect clinical outcomes in adult patients.