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Clostridoides (formerly Clostridium) difficile (C. difficile) is a toxin-producing, gram-positive anaerobic bacillus, commonly implicated in antibiotic-associated diarrhea and pseudomembranous colitis. The true burden of C. difficile infection is unclear in India, as it is likely underdiagnosed and underreported. Its incidence is much higher in oncology patients where it can contribute significantly to morbidity and mortality. There are several challenges in the Indian setting, including lack of uniform availability of testing infrastructure, as well as therapy. Oncology patients further present with a unique set of challenges. This article will review the approach to diagnosis and management of C. difficile- associated diarrhea in India, with a focus on oncology patients. [ABSTRACT FROM AUTHOR]

Background and Objectives: The most common cause of healthcare-associated diarrhea is Clostridium difficile infection (CDI), which causes severe and recurring symptoms. The increase of antibiotic-resistant C. difficile requires alternate treatments. Postbiotics, metabolites produced by probiotics, fight CDI owing to their antibacterial capabilities. This study aims to evaluate the antibacterial, antibiofilm, and anti-toxigenic potential of postbiotics in combating CDI. Materials and Methods: GC-MS evaluated postbiotics from Bifidobacterium bifidum and Lactobacillus plantarum. Disk diffusion and broth microdilution determined C. difficile antibacterial inhibition zones and MICs. Microtiter plates assessed antibiofilm activity. MTT assay evaluated postbiotics anti-viability on HEK293. ELISA testing postbiotic detoxification of toxins A and B. Postbiotics were examined for tcdA and tcdB genes expression using real-time PCR. Results: The most identified B. bifidum and L. plantarum postbiotic compounds were glycolic acid (7.2%) and butyric acid (13.57%). B. bifidum and L. plantarum displayed 13 and 10 mm inhibition zones and 2.5 and 5 mg/ml MICs against C. difficile. B. bifidum reduced biofilm at 1.25 mg/ml by 49% and L. plantarum by 31%. MTT assay showed both postbiotics had little influence on cell viability, which was over 80%. The detoxification power of postbiotics revealed that B. bifidum decreased toxin A and B production more effectively than L. plantarum, and also their related tcdA and tcdB genes expression reduction were statistically significant (p < 0.05). Conclusion: Postbiotics' ability to inhibit bacterial growth, biofilm disruption, and toxin reduction makes them a promising adjunctive for CDI treatment and a good solution to pathogens' antibiotic resistance. [ABSTRACT FROM AUTHOR]

Background: Clostridioides difficile infection (CDI) represents a prevalent and potentially severe health concern linked to the usage of broad-spectrum antibiotics. The aim of this study was to evaluate a new lyophilized product based on human fecal microbiota for transplant, including cost–benefit analysis in the treatment of recurrent or refractory CDI. Methods: The product for fecal microbiota transplant was obtained from two donors. Microbiological, viability, and genomic analysis were evaluated. After validation, a clinical pilot study including recurrent or refractory CDI with 24 patients was performed. Clinical response and 4-week recurrence were the outcome. Cost–benefit analysis compared the fecal microbiota transplant with conventional retreatment with vancomycin or metronidazole. Results: The microbiota for transplant presented significant bacterial viability, with and adequate balance of Firmicutes and Bacteroidetes. The clinical response with the microbiota transplant was 92%. In financial terms, estimated expenditure for CDI solely related to recurrence, based on stochastic modeling, totals USD 222.8 million per year in Brazil. Conclusions: The lyophilized human fecal microbiota for transplant is safe and can be an important step for a new product with low cost, even with genomic sequencing. Fecal microbiota transplantation emerges as a more cost-effective alternative compared to antimicrobials in the retreatment of CDI. [ABSTRACT FROM AUTHOR]

Background and Objectives: Clostridioides difficile infection is a major public health issue, being among the main causes of mortality due to healthcare-associated diarrhea. This study aimed to assess the trends in mortality attributable to Clostridioides difficile infections in European countries over a period of 30 years. Materials and Methods: A descriptive epidemiological study was conducted, with the application of an ecological study design, to evaluate the trends in mortality due to Clostridioides difficile infection in the Central, Eastern, and Western European sub-regions from 1990 to 2019. The Global Burden of Disease study database was used. Trends were evaluated with the joinpoint regression analysis. Results: In both sexes, about 76% of all deaths attributable to Clostridioides difficile infections were recorded in the Western European sub-region in 2019. The age-standardized rates of the burden of Clostridioides difficile infection in 2019 were the highest in the Central European sub-region, followed by the Western European sub-region, while the lowest rates were observed in the Eastern European sub-region. A significantly increasing trend in mortality attributable to Clostridioides difficile infection from 1990 to 2019 was recorded both in males (by +2.1% per year) and females (by +2.8% per year). The burden of Clostridioides difficile infection showed increasing trends in most of the European countries, significantly correlating with the country's development, according to the Human Development Index. Conclusions: The rising burden of Clostridioides difficile infection in European countries in the last few decades suggests a need for improving public health measures, with a focus both on the hospital setting and community. [ABSTRACT FROM AUTHOR]

Single‐domain antibodies (sdAbs), such as VHHs, are increasingly being developed for gastrointestinal (GI) applications against pathogens to strengthen gut health. However, what constitutes a suitable developability profile for applying these proteins in a gastrointestinal setting remains poorly explored. Here, we describe an in vitro methodology for the identification of sdAb derivatives, more specifically divalent VHH constructs, that display extraordinary developability properties for oral delivery and functionality in the GI environment. We showcase this by developing a heterodivalent VHH construct that cross‐inhibits the toxic activity of the glycosyltransferase domains (GTDs) from three different toxinotypes of cytotoxin B (TcdB) from lineages of Clostridium difficile. We show that the VHH construct possesses high stability and binding activity under gastric conditions, in the presence of bile salts, and at high temperatures. We suggest that the incorporation of early developability assessment could significantly aid in the efficient discovery of VHHs and related constructs fit for oral delivery and GI applications. [ABSTRACT FROM AUTHOR]

Introduction: Gastrointestinal infections affect many people annually. The most common bacterial agents involved in these infections are enteropathogenic bacteria and in the continuation of using broad-spectrum antibiotics, Clostridium difficile-associated diarrhea is involved, especially in hospitalized patients. The aim of the present study was to investigate the pattern of antibiotic resistance among enteropathogenic bacteria. Materials and Methods: In this cross-sectional study, 163 samples of patients with diarrhea in Dezful Ganjavian Hospital were examined. The samples were cultured in MacConkey, Hektoen enteric agar and GN broth, and cycloserine cefoxitin fructose agar media and incubated under standard conditions. In order to identify enteropathogenic bacteria, biochemical tests and serological confirmatory tests were used. Antibiotic resistance pattern of the isolates was investigated by Kirby–Bauer disk diffusion susceptibility test. Results: The frequency of pathogenic bacteria includes 41.1% of Shigella flexneri, followed by 41.1% of S. sonnei, 6.7% of Enteropathogenic E. coli, 5.5% of Salmonella enterica Serogroup B, and 5.5% of Shigella dysenteriae. The results revealed a total of 46 patients with orders regarding C. difficile culture, no C. difficile was isolated from the samples. The studied isolates showed the highest resistance to trimethoprim-sulfamethoxazole, and ceftriaxone (88.3%), and the most effective antibiotic in the treatment of patients was ciprofloxacin with 86% sensitivity. Conclusion: Susceptibility to antibiotics was different among the isolates, which shows that the early identification of the infection agent and the selection of the correct antibiotic treatment are effective in improving the gastrointestinal infection and preventing the spread of the infection.

Pseudomembranous colitis (PMC) is a serious condition caused by Clostridium difficile, frequently arising after antimicrobial therapy. In recent years, Clostridium difficile infection rates have been rising and more younger patients have been affected than adult. This case report is about a 3-year-oldboy with clinical, laboratory, and endoscopic findings typical of pseudomembranous colitis, without a history of previous antibiotic therapy.

Abstract In this study, we sought to evaluate the influence of positive pathogens in stool (PPS) on clinical outcomes in critical ill patients with Sepsis-associated acute kidney injury (S-AKI) from intensive care unit. Our sample consisted of 7338 patients, of whom 752 (10.25%) had PPS. We found that the presence of Clostridium difficile (C. difficile) and protists in stool samples was correlated with survival during hospitalization, as well as 30-day and 90-day survival. Interestingly, there was no significant difference in overall survival and 30-day in-hospital survival between the PPS group and the negative pathogens in stool (NPS) control group. However, the cumulative incidence of 90-day infection-related mortality was significantly higher in the PPS group (53 vs. 48%, P = 0.022), particularly in patients with C. difficile in their stool specimens. After adjusting for propensity scores, the results also have statistical significance. These findings suggest that PPS may affect the 90-days survival outcomes of S-AKI, particularly in patients with C. difficile and protists in their stool samples. Further research is warranted to further explore these associations.

Clostridioides difficile (C. difficile) is the predominant causative agent of nosocomial diarrhea worldwide. Infection with C. difficile occurs due to the secretion of large glycosylating toxin proteins, which can lead to toxic megacolon or mortality in susceptible hosts. A critical aspect of C. difficile's biology is its ability to persist asymptomatically within the human host. Individuals harboring asymptomatic colonization or experiencing a single episode of C. difficile infection (CDI) without recurrence exhibit heightened immune responses compared to symptomatic counterparts. The significance of these immune responses cannot be overstated, as they play critical roles in the development, progression, prognosis, and outcomes of CDI. Nonetheless, our current comprehension of the immune responses implicated in CDI remains limited. Therefore, further investigation is imperative to elucidate their underlying mechanisms. This review explores recent advancements in comprehending CDI pathogenesis and how the host immune system response influences disease progression and severity, aiming to enhance our capacity to develop immunotherapy‐based treatments for CDI. Highlights: The progression of Clostridioides difficile infection (CDI) is influenced by various factors, including the use of antibiotics, age, comorbidities, immune gene polymorphisms, and antibody levels.Immune response plays a critical role in controlling both the course and severity of CDI.Immunotherapy holds significant promise for advancing both treatment and prevention strategies for CDI. This encompasses the application of monoclonal antibodies, vaccines, and fecal microbiota transplantation (FMT). [ABSTRACT FROM AUTHOR]

Objectives To determine the frequencies and clonal distributions of putative genetic determinants of resistance to antimicrobials applied for treatment of Clostridioides difficile infection (CDI), as documented in the genomic record. Methods We scanned 26 557 C. difficile genome sequences publicly available from the EnteroBase platform for plasmids, point mutations and gene truncations previously reported to reduce susceptibility to vancomycin, fidaxomicin or metronidazole, respectively. We measured the antimicrobial susceptibility of 143 selected C. difficile isolates. Results The frequency of mutations causing reduced susceptibility to vancomycin and metronidazole, respectively, increased strongly after 2000, peaking at up to 52% of all sequenced C. difficile genomes. However, both mutations declined sharply more recently, reflecting major changes in CDI epidemiology. We detected mutations associated with fidaxomicin resistance in several major genotypes, but found no evidence of international spread of resistant clones. The pCD-METRO plasmid, conferring metronidazole resistance, was detected in a single previously unreported C. difficile isolate, recovered from a hospital patient in Germany in 2008. The pX18-498 plasmid, putatively associated with decreased vancomycin susceptibility, was confined to related, recent isolates from the USA. Phenotype measurements confirmed that most of those genetic features were useful predictors of antibiotic susceptibility, even though ranges of MICs typically overlapped among isolates with and without specific mutations. Conclusions Genomic data suggested that resistance to therapeutic antimicrobial drugs is rare in C. difficile. Public antimicrobial resistance marker databases were not equipped to detect most of the genetic determinants relevant to antibiotic therapy of CDI. [ABSTRACT FROM AUTHOR]

We present the case of a male with end-stage diabetic nephropathy on haemodialysis who initially presented with acute-on-chronic digital ulceration. While awaiting vascular intervention, he became septic with abdominal pain and diarrhoea. Flexible sigmoidoscopy confirmed pseudomembranous colitis secondary to Clostridium difficile. Blood cultures grew Parabacteroides distasonis, a Gram-negative gut anaerobe. Enterobacter cloacae, another Gram-negative anaerobic gut bacilli, was grown in colonic cultures and swabs of the digital ulcers. We hypothesise that the pseudomembranous colitis increased gut translocation and thus led to the systemic spread of both gut anaerobes. This is the first reported case of Parabacteroides distasonis bacteraemia in the context of Clostridium difficile infection. Our patient recovered with antibiotics and went on to have vascular intervention for his digital ulceration. [ABSTRACT FROM AUTHOR]

In this study, we sought to evaluate the influence of positive pathogens in stool (PPS) on clinical outcomes in critical ill patients with Sepsis-associated acute kidney injury (S-AKI) from intensive care unit. Our sample consisted of 7338 patients, of whom 752 (10.25%) had PPS. We found that the presence of Clostridium difficile (C. difficile) and protists in stool samples was correlated with survival during hospitalization, as well as 30-day and 90-day survival. Interestingly, there was no significant difference in overall survival and 30-day in-hospital survival between the PPS group and the negative pathogens in stool (NPS) control group. However, the cumulative incidence of 90-day infection-related mortality was significantly higher in the PPS group (53 vs. 48%, P = 0.022), particularly in patients with C. difficile in their stool specimens. After adjusting for propensity scores, the results also have statistical significance. These findings suggest that PPS may affect the 90-days survival outcomes of S-AKI, particularly in patients with C. difficile and protists in their stool samples. Further research is warranted to further explore these associations. [ABSTRACT FROM AUTHOR]

Introduction: Gastrointestinal infections affect many people annually. The most common bacterial agents involved in these infections are enteropathogenic bacteria and in the continuation of using broad‑spectrum antibiotics, Clostridium difficile‑associated diarrhea is involved, especially in hospitalized patients. The aim of the present study was to investigate the pattern of antibiotic resistance among enteropathogenic bacteria. Materials and Methods: In this cross‑sectional study, 163 samples of patients with diarrhea in Dezful Ganjavian Hospital were examined. The samples were cultured in MacConkey, Hektoen enteric agar and GN broth, and cycloserine cefoxitin fructose agar media and incubated under standard conditions. In order to identify enteropathogenic bacteria, biochemical tests and serological confirmatory tests were used. Antibiotic resistance pattern of the isolates was investigated by Kirby–Bauer disk diffusion susceptibility test. Results: The frequency of pathogenic bacteria includes 41.1% of Shigella flexneri, followed by 41.1% of S. sonnei, 6.7% of Enteropathogenic E. coli, 5.5% of Salmonella enterica Serogroup B, and 5.5% of Shigella dysenteriae. The results revealed a total of 46 patients with orders regarding C. difficile culture, no C. difficile was isolated from the samples. The studied isolates showed the highest resistance to trimethoprim‑sulfamethoxazole, and ceftriaxone (88.3%), and the most effective antibiotic in the treatment of patients was ciprofloxacin with 86% sensitivity. Conclusion: Susceptibility to antibiotics was different among the isolates, which shows that the early identification of the infection agent and the selection of the correct antibiotic treatment are effective in improving the gastrointestinal infection and preventing the spread of the infection. [ABSTRACT FROM AUTHOR]

Pseudomembranous colitis (PMC) is a serious condition caused by Clostridium difficile, frequently arising after antimicrobial therapy. In recent years, Clostridium difficile infection rates have been rising and more younger patients have been affected than adult. This case report is about a 3-year-old boy with clinical, laboratory, and endoscopic findings typical of pseudomembranous colitis, without a history of previous antibiotic therapy. [ABSTRACT FROM AUTHOR]

Background Because interventions are available to prevent further recurrence in patients with recurrent Clostridioides difficile infection (rCDI), we identified predictors of multiple rCDI (mrCDI) in adults at the time of presentation with initial CDI (iCDI). Methods iCDI was defined as a positive C difficile test in any clinical setting during January 2018–August 2019 in a person aged ≥18 years with no known prior positive test. rCDI was defined as a positive test ≥14 days from the previous positive test within 180 days after iCDI; mrCDI was defined as ≥2 rCDI. We performed multivariable logistic regression analysis. Results Of 18 829 patients with iCDI, 882 (4.7%) had mrCDI; 437 with mrCDI and 7484 without mrCDI had full chart reviews. A higher proportion of patients with mrCDI than without mrCDI were aged ≥65 years (57.2% vs 40.7%; P <.0001) and had healthcare (59.1% vs 46.9%; P <.0001) and antibiotic (77.3% vs 67.3%; P <.0001) exposures in the 12 weeks preceding iCDI. In multivariable analysis, age ≥65 years (adjusted odds ratio [aOR], 1.91; 95% confidence interval [CI], 1.55–2.35), chronic hemodialysis (aOR, 2.28; 95% CI, 1.48–3.51), hospitalization (aOR, 1.64; 95% CI, 1.33–2.01), and nitrofurantoin use (aOR, 1.95; 95% CI, 1.18–3.23) in the 12 weeks preceding iCDI were associated with mrCDI. Conclusions Patients with iCDI who are older, on hemodialysis, or had recent hospitalization or nitrofurantoin use had increased risk of mrCDI and may benefit from early use of adjunctive therapy to prevent mrCDI. If confirmed, these findings could aid in clinical decision making and interventional study designs. [ABSTRACT FROM AUTHOR]

Background: Recurrent Clostridium difficile infection (rCDI) is a rising problem in children with chronic diseases. Fecal microbiota transplantation (FMT) is a recent alternative for rCDI patients who do not respond to conventional treatment. FMT could have an additional positive effect on the intestinal dysbiosis and accumulation of uremic retention molecules (URM) associated with chronic kidney disease (CKD). Our aim was to investigate the clinical efficacy of FMT for rCDI in children with CKD together with the effect on dysbiosis and URM levels. Methods: We analyzed stool and blood samples before and until 3 months after FMT in 3 children between 4 and 8 years old with CKD and rCDI. The microbiome was analyzed by 16 s rRNA sequencing. URM were analyzed with ultra-performance liquid chromatography-tandem mass spectrometry. CRP and fecal calprotectin were analyzed as parameters for systemic and gut inflammation, respectively. Results: CDI resolved after FMT in all three without adverse events; one patient needed a second FMT. No significant effect on CRP and calprotectin was observed. Stool samples demonstrated a reduced richness and bacterial diversity which did not improve after FMT. We did observe a trend in the decrease of specific URM up to 3 months after FMT. Conclusion: FMT is an effective treatment for rCDI in patients with CKD. Analysis of the microbiome showed an important intestinal dysbiosis that, besides a significant reduction in Clostridium difficile, did not significantly change after FMT. A trend for reduction was seen in some of the measured URM after FMT. [ABSTRACT FROM AUTHOR]

Understanding the potential antimicrobial properties of natural compounds and their impacts on Clostridioides difficile virulence factors may aid in developing alternative strategies for preventing and treating C. difficile infections (CDI). In this study, we investigated the bactericidal effects of ginger oil (GO), peppermint oil (PO), curcumin (CU), cinnamon aldehyde (CI), and trans-cinnamaldehyde (TCI) on the adhesion and biofilm disruption of C. difficile. We used three reference and five clinical C. difficile strains of different ribotypes. The bactericidal activity was assessed using the broth microdilution method. The adhesion was evaluated using human epithelial cell lines, and biofilm formation was visualized by confocal laser scanning microscopy. All tested strains exhibited susceptibility to CU, with minimum inhibitory concentration (MIC) values ranging from 128 µg/mL to 2048 µg/mL. Similarly, all strains were susceptible to CI and TCI, with MIC values ranging from 6.25% (v/v) to 25% (v/v). Most of the tested substances reduced the adhesion of C. difficile strains, while two tested strains showed significantly higher adhesion when co-incubated with the tested substances. Similar observations were made for biofilm formation, with observed density and morphology varied depending on the strain. In conclusion, the tested products demonstrated bactericidal activity and reduced the adhesion of C. difficile strains. They may be considered for further studies as potential antimicrobial agents targeting biofilm-related infections. [ABSTRACT FROM AUTHOR]

Objective: Fecal calprotectin (FC) has an essential role in differentiating inflammatory diarrhea from functional diarrhea in an outpatient setting; however, its role in nosocomial diarrhea remains not well explored. Materials and Methods: This is a prospective observational study. We included adult inpatients with nosocomial diarrhea and categorized them into diarrhea likely (group A) and unlikely (group B) to have lesions in the colonic mucosa. Group A included infectious diarrhea such as Clostridium difficile and ischemic colitis. Group B comprised tube-feeding diarrhea, non-C. difficile antibiotic-associated diarrhea, and drug-induced diarrhea. The FC levels were compared between the two groups. Results: 135 patients were included, 45 in group A and 90 in group B. Median FC was 902 mg/kg (interquartile range [IQR] 549-2,175) of feces in group A, significantly higher than the median level of 377 mg/kg (IQR 141-664) of feces in group B (p<0.001). The area under the receiver operating characteristic curve was 0.798 (95% confidence interval: 0.717-0.879). At the standard cutoff of 50 mg/kg of feces, the sensitivity and specificity were 97.8% and 7.8%, respectively. Conclusion: FC was significantly higher in nosocomial diarrhea likely to have mucosal lesions; however, its clinical usefulness was limited due to poor specificity. Trial registration: The trial was registered at ClinicalTrials.gov. (reg. no. NCT04491799. Registered on 26/04/2020). [ABSTRACT FROM AUTHOR]

Background and Objectives: The most common cause of healthcare-associated diarrhea is Clostridium difficile infection (CDI), which causes severe and recurring symptoms. The increase of antibiotic-resistant C. difficile requires alternate treatments. Postbiotics, metabolites produced by probiotics, fight CDI owing to their antibacterial capabilities. This study aims to evaluate the antibacterial, antibiofilm, and anti-toxigenic potential of postbiotics in combating CDI. Materials and Methods: GC-MS evaluated postbiotics from Bifidobacterium bifidum and Lactobacillus plantarum. Disk diffusion and broth microdilution determined C. difficile antibacterial inhibition zones and MICs. Microtiter plates assessed antibiofilm activity. MTT assay evaluated postbiotics anti-viability on HEK293. ELISA testing postbiotic detoxification of toxins A and B. Postbiotics were examined for tcdA and tcdB genes expression using real-time PCR. Results: The most identified B. bifidum and L. plantarum postbiotic compounds were glycolic acid (7.2%) and butyric acid (13.57%). B. bifidum and L. plantarum displayed 13 and 10 mm inhibition zones and 2.5 and 5 mg/ml MICs against C. difficile. B. bifidum reduced biofilm at 1.25 mg/ml by 49% and L. plantarum by 31%. MTT assay showed both postbiotics had little influence on cell viability, which was over 80%. The detoxification power of postbiotics revealed that B. bifidum decreased toxin A and B production more effectively than L. plantarum, and also their related tcdA and tcdB genes expression reduction were statistically significant (p < 0.05). Conclusion: Postbiotics' ability to inhibit bacterial growth, biofilm disruption, and toxin reduction makes them a promising adjunctive for CDI treatment and a good solution to pathogens' antibiotic resistance.

Masaad Saeed Almutairi,1 Faris S Alnezary,2 Rasil O Alsuwaylim,1 Ibrahim Alsulaymi,1 Omar A Almohammed,3,4 Abrar K Thabit5 1Department of Pharmacy Practice, College of Pharmacy, Qassim University, Qassim, Saudi Arabia; 2Department of Pharmacy Practice, College of Pharmacy, Taibah University, Madinah, Saudi Arabia; 3Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 4Pharmacoeconomics Research Unit, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 5Pharmacy Practice Department, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi ArabiaCorrespondence: Masaad Saeed Almutairi, Department of Pharmacy Practice, College of Pharmacy, Qassim University, Qassim, 51452, Saudi Arabia, Tel +966557523133, Email mas.almutairi@qu.edu.saIntroduction: Diagnosis of Clostridioides difficile infection (CDI) depends on clinical presentation and laboratory testing. Stool diagnostic tests are essential for effective detection of toxigenic C. difficile strains. No study to date has evaluated the readability of microbiology labs in Saudi Arabia to test for CDI and evaluated the knowledge and practice of healthcare providers regarding CDI management. Therefore, this study aimed to assess the knowledge and practice of healthcare providers in Saudi Arabia regarding CDI diagnosis and treatment.Methods: A cross-sectional, descriptive, questionnaire-based study was conducted on healthcare providers in Saudi Arabia, primarily physicians and clinical pharmacists. The questionnaire was developed based on a literature review and input from infectious diseases experts. The questionnaire was administered online. Data were analyzed using descriptive and inferential statistics.Results: Of 183 respondents, 27.9% had adequate knowledge on CDI diagnosis and management. The majority were internal medicine specialists (37.7%) working in governmental or semi-governmental hospitals (80.9%) in central (46.6%) or southern (30.1%) regions of Saudi Arabia. Most participants assessed laxative use (86.3%) and reported positive C. difficile specimens to infection control (67.2%). However, knowledge varied, with 57.4% supporting unnecessary retesting and 53% assuming positive PCR test indicates moderate CDI probability. Factors such as specialization, hospital accreditation status, and bed capacity influenced knowledge levels (p< 0.01 for all factors).Conclusion: The study revealed a significant knowledge gap among Saudi healthcare providers regarding CDI diagnosis, management, and severity classification, highlighting the need for improved education and adherence to guidelines to improve patient outcomes and reduce recurrence risks.Keywords: Clostridioides difficile, Clostridium difficile, diagnosis, polymerase chain reaction, knowledge, Saudi Arabia

Abstract Background Reactive arthritis and septic arthritis rarely present concomitantly in the same joint and patient. Reactive arthritis presenting after coronavirus disease 2019 is also exceedingly rare, with less than 30 cases reported thus far. Less common pathogens such as Clostridium difficile have been reported to cause reactive arthritis, especially in patients with a positive human leukocyte antigen B27, and therefore should be considered in diagnostic algorithms. The aim of this case report is to highlight the difficulties and precautions in discerning and diagnosing patients presenting with sudden swelling of the knee. Case presentation We report the case of a 70-year-old Caucasian male with a recent history of coronavirus disease 2019 upper respiratory infection and diarrhea and negating trauma, who presented with a swollen and painful knee. Pain and swelling worsened and inflammatory parameters increased after an intraarticular corticosteroid injection. The patient was therefore treated with arthroscopic lavage and intravenous antibiotics for suspected septic arthritis. Synovial fluid and synovium samples were taken and sent for microbiological analysis. Synovial fluid cytology showed increased leukocytes at 10,980 × 106/L, while polymerase chain reaction and cultures came back sterile. Clostridium difficile toxin was later detected from a stool sample and the patient was treated with oral vancomycin. The patient was tested for the presence of human leukocyte antigen B27, which was positive. We present a review of the literature about the challenges of distinguishing septic from reactive arthritis, and about the mechanisms that predispose certain patients to this rheumatological disease. Conclusions It is still a challenge to differentiate between septic and reactive arthritis of the knee, and it is even more challenging to identify the exact cause of reactive arthritis. This case report of a human leukocyte antigen-B27-positive patient highlights the necessity of contemplating different, less common causes of a swollen knee joint as a differential diagnosis of an apparent septic infection, especially in the coronavirus disease 2019 era. Treating the patient for septic arthritis prevented any possible complications of such a condition, while treating the C. difficile infection contributed to the substantial relief of symptoms.

Aim: Clostridium difficile (C. diff.) infection (CDI) is the major contributor of nosocomial infection globally. The current review aims to provide a comprehensive understanding of the mechanisms behind the critical role of intestinal 3Ms (i.e., microbiota, metabolome, and metabolism) in the pathogenesis and prophylaxis of recurrent CDI. Material and methods: Primarily centering around the mechanisms related to gut microbiota-dependent risk factors, we have discussed why gut microbial diversity and abundance are critical determinants of infection risk. Additionally, emphasis has been given on the intestine-specific molecular mechanisms related to the modulation of the global metabolome and signaling processes which trigger disease susceptibility. Key findings: Patients with CDI harbor altered gut microbial phenotype compared to healthy individuals and asymptomatic careers. Clinical and experimental (germ-free mice, mono-strain interactions, longitudinal trails) evidences indicate that alterations of the gut microbiota due to antibiotic exposure, advanced age, immunocompromised conditions and prolonged hospitalization could lead to gastrointestinal colonization of C. diff. Further, the gut microbiota mediated modulation of the mucosal signaling (farnesoid X receptor, aryl hydrocarbon receptor, conserved nuclear receptors, immunological signaling) and the luminal metabolomic signatures play critical role in the disease susceptibility and progression. The use of live biotherapeutics and fecal microbiota transplantation are currently the most suitable prophylactic strategy against recurrent CDI. Significance: The current review highlights the host-microbiota interaction which dictates the intestinal signaling responsible for the pathogenesis of recurrent CDI.

Introduction: Postoperative Clostridium difficile infection (CDI) has associated morbidity, but it is unknown how it impacts different operations. We sought to determine the incidence and postoperative morbidity following abdominal surgery.Method: The National Surgical Quality Improvement Program database (2015-2019) was utilized to evaluate adult (≥18 years-old) patients who developed CDI following laparoscopic abdominal operations. Univariate and multivariate analysis were performed to evaluate outcomes.Results: A total of 973 338 patients were studied and the overall incidence of CDI was .3% within 30 days of operation. Colorectal surgery had the highest incidence of CDI (1601/167 949,1.0%) with significantly longer mean length of stay (LOS) (8.0 days± 9.0, P < .01) compared to other surgical procedures. CDI patients also had a longer mean length of stay (6.6± 8.0 vs 2.1 ± 3.6 days, P < .01) and increased mortality (1.8% vs .2%, AOR: 4.64, CI: 3.45-5.67, P < .01) compared to patients without CDI.Conclusions: This national analysis demonstrates that CDI is a significant complication following abdominal surgery and is associated with increased LOS and mortality. Furthermore, laparoscopic colorectal surgery appears to have the greatest risk of CDI. Future research is needed to determine the exact cause in order to decrease the incidence of CDI by reconsidering the protocol of antibiotic use within the high-risk population.

Clostridioides difficile infection (CDI) is a serious healthcare-associated disease, causing symptoms such as diarrhea and pseudomembranous colitis. The major virulence factors responsible for the disease symptoms are two secreted cytotoxic proteins, TcdA and TcdB. A parenteral vaccine based on formaldehyde-inactivated TcdA and TcdB supplemented with alum adjuvant, has previously been investigated in humans but resulted in an insufficient immune response. In search for an improved response, we investigated a novel toxin inactivation method and a novel, potent adjuvant. Inactivation of toxins by metal-catalyzed oxidation (MCO) was previously shown to preserve neutralizing epitopes and to annihilate reversion to toxicity. The immunogenicity and safety of TcdA and TcdB inactivated by MCO and combined with a novel carbohydrate fatty acid monosulphate ester-based (CMS) adjuvant were investigated in rabbits. Two or three intramuscular immunizations generated high serum IgG and neutralizing antibody titers against both toxins. The CMS adjuvant increased antibody responses to both toxins while an alum adjuvant control was effective only against TcdA. Systemic safety was evaluated by monitoring body weight, body temperature, and analysis of red and white blood cell counts shortly after immunization. Local safety was assessed by histopathologic examination of the injection site at the end of the study. Body weight gain was constant in all groups. Body temperature increased up to 1 ˚C one day after the first immunization but less after the second or third immunization. White blood cell counts, and percentage of neutrophils increased one day after immunization with CMS-adjuvanted vaccines, but not with alum. Histopathology of the injection sites 42 days after the last injection did not reveal any abnormal tissue reactions. From this study, we conclude that TcdA and TcdB inactivated by MCO and combined with CMS adjuvant demonstrated promising immunogenicity and safety in rabbits and could be a candidate for a vaccine against CDI. [ABSTRACT FROM AUTHOR]

Clostridioides difficile (C difficile) is one of the most common health care–associated infections that negatively impact patient care and health care costs. This study takes a unique approach to C difficile infection (CDI) control by investigating key prevention obstacles through the perspectives of Stanford health care (SHC) frontline health care personnel. An anonymous qualitative survey was distributed at SHC, focusing on knowledge and practice of CDI prevention guidelines, as well as education, communication, and perspectives regarding CDI at SHC. 112 survey responses were analyzed. Our findings unveiled gaps in personnel's knowledge of C difficile diagnostic guidelines and revealed a need for targeted communication and guideline-focused education. Health care staff shared preferences and recommendations, with the majority recommending enhanced communication of guidelines and information as a strategy for reducing CDI rates. The findings were then used to design and propose internal recommendations for SHC to mitigate the gaps found. Many guidelines and improvement strategies are based on strong scientific and medical foundations; however, it is important to ask whether these guidelines are effectively translated into practice. Frontline health care workers hold empirical perspectives that could be key in infection control. Our findings emphasize the importance of including frontline health care personnel in infection prevention decision-making processes and the strategies presented here can be applied to mitigating infections in different health care settings. • C difficile infection prevention at a quaternary academic health care center. • Qualitative analysis that highlights frontline health care workers' perspectives. • Evaluating whether prevention guidelines are effectively translated into practice. • Inclusion of health care teams in infection prevention decision-making processes. • Proposal of recommendations for sustainable infection prevention and control. [ABSTRACT FROM AUTHOR]

Objectives: Fecal microbiota transplantation (FMT) is an emerging option for recurrent or refractory Clostridium difficile-associated diarrhea (CDAD). We describe a single-center experience of FMT in hematopoietic stem cell transplant (HSCT) recipients with CDAD in India. Methods: A prospective observational study of HSCT recipients with CDAD who received FMT in our center. Results: A total of 13 patients were included. All the patients were allogenic HSCT recipients; FMT was performed in seven patients due to refractory CDAD, in five patients due to the presence of both CDAD and graft vs host disease (GVHD), and in 1 patient due to recurrent CDAD. The approach to FMT was colonoscopic in 10 (77%) patients. Only one patient reported bacteremia and one patient had candidemia, both of which were unrelated to FMT. Of the 10 patients who had complete resolution of CDAD, only one patient presented with a recurrence of CDAD within 8 weeks post-FMT. Conclusion: This is the first study from India using FMT as a therapeutic modality for CDAD in the setting of HSCT. Here we demonstrate that FMT in India is an effective option, especially when patients have refractory CDAD, recurrent CDAD, or both GVHD and CDAD. Further studies should explore the efficacy and feasibility of FMT in India. [ABSTRACT FROM AUTHOR]

Background: Reactive arthritis and septic arthritis rarely present concomitantly in the same joint and patient. Reactive arthritis presenting after coronavirus disease 2019 is also exceedingly rare, with less than 30 cases reported thus far. Less common pathogens such as Clostridium difficile have been reported to cause reactive arthritis, especially in patients with a positive human leukocyte antigen B27, and therefore should be considered in diagnostic algorithms. The aim of this case report is to highlight the difficulties and precautions in discerning and diagnosing patients presenting with sudden swelling of the knee. Case presentation: We report the case of a 70-year-old Caucasian male with a recent history of coronavirus disease 2019 upper respiratory infection and diarrhea and negating trauma, who presented with a swollen and painful knee. Pain and swelling worsened and inflammatory parameters increased after an intraarticular corticosteroid injection. The patient was therefore treated with arthroscopic lavage and intravenous antibiotics for suspected septic arthritis. Synovial fluid and synovium samples were taken and sent for microbiological analysis. Synovial fluid cytology showed increased leukocytes at 10,980 × 106/L, while polymerase chain reaction and cultures came back sterile. Clostridium difficile toxin was later detected from a stool sample and the patient was treated with oral vancomycin. The patient was tested for the presence of human leukocyte antigen B27, which was positive. We present a review of the literature about the challenges of distinguishing septic from reactive arthritis, and about the mechanisms that predispose certain patients to this rheumatological disease. Conclusions: It is still a challenge to differentiate between septic and reactive arthritis of the knee, and it is even more challenging to identify the exact cause of reactive arthritis. This case report of a human leukocyte antigen-B27-positive patient highlights the necessity of contemplating different, less common causes of a swollen knee joint as a differential diagnosis of an apparent septic infection, especially in the coronavirus disease 2019 era. Treating the patient for septic arthritis prevented any possible complications of such a condition, while treating the C. difficile infection contributed to the substantial relief of symptoms. [ABSTRACT FROM AUTHOR]

Clostridium difficile infection (CDI) is a bacterial infection caused by Clostridium difficile (CD). The incidence and prevalence of CDI have increased, presenting a significant problem. Treatment of non-severe, initial CDI generally involves the administration of the antibiotic vancomycin as recommended by the guidelines. However, discrepancies still exist between the use of low and high dose of vancomycin in clinical practice, generating confusion for pharmacists due to the inconsistency of prescribed oral vancomycin patterns. The aim of this study was to investigate the prescribing patterns of oral vancomycin and its outcomes in adult patients diagnosed with non-severe, initial CDI. A retrospective chart review study was performed in 67 patients between January 1, 2015 and October 1, 2022. We analyzed the patterns of prescribed oral vancomycin including dose, frequency, and duration. Fisher's exact test was used to compare oral vancomycin doses and their clinical outcomes. Of the 67 patients, 44 participants met the inclusion criteria. Four prescribing patterns were discovered: 1) vancomycin 125 mg PO every 6 hours (81.8%), 2) vancomycin 250 mg PO every 6 hours (9.1%), 3) vancomycin 500 mg PO every 6 hours (2.3%), and 4) others (6.8%) (250 mg PO every 24 hours and 125 mg PO every 8 hours). The association between low and high dose of oral vancomycin and clinical outcomes was found to have no statistically significant difference (p=1.000). The results from this study could be used as fundamental information for protocol development in clinical settings. [ABSTRACT FROM AUTHOR]

The article discusses the use of a prescription microbiome therapeutic called Fecal Microbiota Live-jslm for the treatment of recurrent Clostridioides difficile infection (CDI). The therapy has been approved by the US Food and Drug Administration (FDA) and has shown efficacy and safety in clinical trials. The article provides information on donor recruitment, manufacturing processes, and clinical trial data. It also discusses the potential use of the therapy for other microbiome-associated conditions. The text is written from a neutral perspective and provides references to two articles published in medical journals. [Extracted from the article]

Background: This study was performed to determine the magnitude of Clostridioides difficile infection (CDI) in a tertiary care hospital in patients with antibiotic associated diarrhea (AAD) and to study the risk factors associated with this disease. Methods: A descriptive study was conducted in the department of Microbiology in a tertiary care hospital during December 2019 to May 2021. Stool samples were collected from patients with signs and symptoms of AAD who had been consuming antibiotic or anticancer drugs durng six weeks before the sampling. The samples were subjected to C. difficile glutamate dehydrogenase (GDH) enzyme and CD toxin A & B detection by Enzyme Linked Fluorescent Assay (ELFA). Patient’s demographic features and clinical details were noted and statistically correlated with the test results. Results: Among the total 70 samples tested 20 (28%) were positive for GDH alone and 12 (17%) were positive for both GDH and CD toxin A and B. Fluoroquinolones was a significant risk factor in the study. Sepsis and colitis was found to have significant association with C.difficile infection in our study. The crude mortality rate was 17%. Conclusion: Prompt and precise diagnosis and knowledge about the risk factors of CDI helps in effective management and prevention of CDI. [ABSTRACT FROM AUTHOR]

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ABSTRACT In a healthy colon, the stratified mucus layer serves as a crucial innate immune barrier to protect the epithelium from microbes. Mucins are complex glycoproteins that serve as a nutrient source for resident microflora and can be exploited by pathogens. We aimed to understand how the intestinal pathogen, Clostridioides difficile, independently uses or manipulates mucus to its benefit, without contributions from members of the microbiota. Using a 2-D primary human intestinal epithelial cell model to generate physiologic mucus, we assessed C. difficile-mucus interactions through growth assays, RNA-Seq, biophysical characterization of mucus, and contextualized metabolic modeling. We found that host-derived mucus promotes C. difficile growth both in vitro and in an infection model. RNA-Seq revealed significant upregulation of genes related to central metabolism in response to mucus, including genes involved in sugar uptake, the Wood-Ljungdahl pathway, and the glycine cleavage system. In addition, we identified differential expression of genes related to sensing and transcriptional control. Analysis of mutants with deletions in highly upregulated genes reflected the complexity of C. difficile-mucus interactions, with potential interplay between sensing and growth. Mucus also stimulated biofilm formation in vitro, which may in turn alter the viscoelastic properties of mucus. Context-specific metabolic modeling confirmed differential metabolism and the predicted importance of enzymes related to serine and glycine catabolism with mucus. Subsequent growth experiments supported these findings, indicating mucus is an important source of serine. Our results better define responses of C. difficile to human gastrointestinal mucus and highlight flexibility in metabolism that may influence pathogenesis.IMPORTANCEClostridioides difficile results in upward of 250,000 infections and 12,000 deaths annually in the United States. Community-acquired infections continue to rise, and recurrent disease is common, emphasizing a vital need to understand C. difficile pathogenesis. C. difficile undoubtedly interacts with colonic mucus, but the extent to which the pathogen can independently respond to and take advantage of this niche has not been explored extensively. Moreover, the metabolic complexity of C. difficile remains poorly understood but likely impacts its capacity to grow and persist in the host. Here, we demonstrate that C. difficile uses native colonic mucus for growth, indicating C. difficile possesses mechanisms to exploit the mucosal niche. Furthermore, mucus induces metabolic shifts and biofilm formation in C. difficile, which has potential ramifications for intestinal colonization. Overall, our work is crucial to better understand the dynamics of C. difficile-mucus interactions in the context of the human gut.

This issue of the Biomedical Journal features a special section exploring mycobiota. Three articles examine the role of fungi in common metabolic disorders in, Clostridium difficile infection, and in immunocompromised patients. Additionally, the potential and challenges of the metaverse in healthcare are reviewed, alongside a holistic approach to improve patient outcomes in pancreatic cancer. In this issue also possible mechanism contributing to long COVID are discussed, as well as biomarkers that effectively predict sepsis outcomes, and key targets in osteosarcoma progression. Moreover, factors leading to peri-intubation cardiac arrest are analyzed, healthcare strategies from various regions are employed to predict cardiovascular events in Asian populations, two approaches to cavernous sinus dural arteriovenous fistula are compared, and a combination therapy against soft tissue sarcoma is presented.

Abstract Clostridioides difficile (C. difficile) is the predominant causative agent of nosocomial diarrhea worldwide. Infection with C. difficile occurs due to the secretion of large glycosylating toxin proteins, which can lead to toxic megacolon or mortality in susceptible hosts. A critical aspect of C. difficile's biology is its ability to persist asymptomatically within the human host. Individuals harboring asymptomatic colonization or experiencing a single episode of C. difficile infection (CDI) without recurrence exhibit heightened immune responses compared to symptomatic counterparts. The significance of these immune responses cannot be overstated, as they play critical roles in the development, progression, prognosis, and outcomes of CDI. Nonetheless, our current comprehension of the immune responses implicated in CDI remains limited. Therefore, further investigation is imperative to elucidate their underlying mechanisms. This review explores recent advancements in comprehending CDI pathogenesis and how the host immune system response influences disease progression and severity, aiming to enhance our capacity to develop immunotherapy‐based treatments for CDI.

ABSTRACT Paeniclostridium sordellii hemorrhagic toxin (TcsH) and Clostridioides difficile toxin A (TcdA) are two major members of the large clostridial toxin (LCT) family. These two toxins share ~87% similarity and are known to cause severe hemorrhagic pathology in animals. Yet, the pathogenesis of their hemorrhagic toxicity has been mysterious for decades. Here, we examined the liver injury after systemic exposure to different LCTs and found that only TcsH and TcdA induce overt hepatic hemorrhage. By investigating the chimeric and truncated toxins, we demonstrated that the enzymatic domain of TcsH alone is not sufficient to determine its potent hepatic hemorrhagic toxicity in mice. Likewise, the combined repetitive oligopeptide (CROP) domain of TcsH/TcdA alone also failed to explain their strong hemorrhagic activity in mice. Lastly, we showed that disrupting the first two short repeats of CROPs in TcsH and TcdA impaired hemorrhagic toxicity without causing overt changes in cytotoxicity and lethality. These findings lead to a deeper understanding of toxin-induced hemorrhage and the pathogenesis of LCTs and could be insightful in developing therapeutic avenues against clostridial infections.IMPORTANCEPaeniclostridium sordellii and Clostridioides difficile infections often cause hemorrhage in the affected tissues and organs, which is mainly attributed to their hemorrhagic toxins, TcsH and TcdA. In this study, we demonstrate that TcsH and TcdA, but not other related toxins. including Clostridioides difficile toxin B and TcsL, induce severe hepatic hemorrhage in mice. We further determine that a small region in TcsH and TcdA is critical for the hemorrhagic toxicity but not cytotoxicity or lethality of these toxins. Based on these results, we propose that the hemorrhagic toxicity of TcsH and TcdA is due to an uncharacterized mechanism, such as the presence of an unknown receptor, and future studies to identify the interactive host factors are warranted.

Background: Clostridioides difficile infection (CDI) represents a prevalent and potentially severe health concern linked to the usage of broad-spectrum antibiotics. The aim of this study was to evaluate a new lyophilized product based on human fecal microbiota for transplant, including cost–benefit analysis in the treatment of recurrent or refractory CDI. Methods: The product for fecal microbiota transplant was obtained from two donors. Microbiological, viability, and genomic analysis were evaluated. After validation, a clinical pilot study including recurrent or refractory CDI with 24 patients was performed. Clinical response and 4-week recurrence were the outcome. Cost–benefit analysis compared the fecal microbiota transplant with conventional retreatment with vancomycin or metronidazole. Results: The microbiota for transplant presented significant bacterial viability, with and adequate balance of Firmicutes and Bacteroidetes. The clinical response with the microbiota transplant was 92%. In financial terms, estimated expenditure for CDI solely related to recurrence, based on stochastic modeling, totals USD 222.8 million per year in Brazil. Conclusions: The lyophilized human fecal microbiota for transplant is safe and can be an important step for a new product with low cost, even with genomic sequencing. Fecal microbiota transplantation emerges as a more cost-effective alternative compared to antimicrobials in the retreatment of CDI.

Background and Objectives: Clostridioides difficile infection is a major public health issue, being among the main causes of mortality due to healthcare-associated diarrhea. This study aimed to assess the trends in mortality attributable to Clostridioides difficile infections in European countries over a period of 30 years. Materials and Methods: A descriptive epidemiological study was conducted, with the application of an ecological study design, to evaluate the trends in mortality due to Clostridioides difficile infection in the Central, Eastern, and Western European sub-regions from 1990 to 2019. The Global Burden of Disease study database was used. Trends were evaluated with the joinpoint regression analysis. Results: In both sexes, about 76% of all deaths attributable to Clostridioides difficile infections were recorded in the Western European sub-region in 2019. The age-standardized rates of the burden of Clostridioides difficile infection in 2019 were the highest in the Central European sub-region, followed by the Western European sub-region, while the lowest rates were observed in the Eastern European sub-region. A significantly increasing trend in mortality attributable to Clostridioides difficile infection from 1990 to 2019 was recorded both in males (by +2.1% per year) and females (by +2.8% per year). The burden of Clostridioides difficile infection showed increasing trends in most of the European countries, significantly correlating with the country’s development, according to the Human Development Index. Conclusions: The rising burden of Clostridioides difficile infection in European countries in the last few decades suggests a need for improving public health measures, with a focus both on the hospital setting and community.