Clostridium Difficile Research Articles

Deep learning-based prediction of Clostridioides difficile infection caused by antibiotics using longitudinal electronic health records

Clostridioides difficile infection (CDI) is a major cause of antibiotic-associated diarrhea and colitis. It is recognized as one of the most significant hospital-acquired infections. Although CDI can develop severe complications and spores of Clostridioides difficile can be transmitted by the fecal-oral route, CDI is occasionally overlooked in clinical settings. Thus, it is necessary to monitor high CDI risk groups, particularly those undergoing antibiotic treatment, to prevent complications and spread. We developed and validated a deep learning-based model to predict the occurrence of CDI within 28 days after starting antibiotic treatment using longitudinal electronic health records. For each patient, timelines of vital signs and laboratory tests with a 35-day monitoring period and a patient information vector consisting of age, sex, comorbidities, and medications were constructed. Our model achieved the prediction performance with an area under the receiver operating characteristic curve of 0.952 (95% CI: 0.932–0.973) in internal validation and 0.972 (95% CI: 0.968–0.975) in external validation. Platelet count and body temperature emerged as the most important features. The risk score, the output value of the model, exhibited a consistent increase in the CDI group, while the risk score in the non-CDI group either maintained its initial value or decreased. Using our CDI prediction model, high-risk patients requiring symptom monitoring can be identified. This could help reduce the underdiagnosis of CDI, thereby decreasing transmission and preventing complications.

Impact of in ovo administration of xylo- and mannooligosaccharides on broiler chicken gut health

The intestinal mucosa creates a connection between the gut microbiota and the host. This study aimed to modify the gut microbiota of broiler chickens by in ovo stimulation with xylo-oligosaccharide (XOS) and manno-oligosaccharide (MOS) prebiotics and to determine the changes occurring in specific gut segments. Three hundred incubated eggs of Ross 308 broiler chickens on the 12th d of incubation were injected with: saline (control), xylotriose (XOS3), xylotetrose (XOS4), mannotriose (MOS3) or mannotetrose (MOS4). Tissue and digesta samples were collected post-mortem from 8 randomly selected individuals from each group, on d 42 after hatching. Gene expression analysis in the cecum and ileum was performed by RT-qPCR for a panel of genes: innate immune response genes (IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, IL-1β, IFNγ, IFNβ), nutrient sensing and nutrient transport genes (FFAR2, FFAR4, GLUT1, GLUT2, GLUT5), host defence peptides (AvBD1, CATHL2), and barrier function genes (MUC6, CLDN1, TJAP). The relative abundance of bacteria was determined by qPCR for individual bacteria (Akkermansia muciniphilla, Bifidobacterium spp., Clostridium difficile, Escherichia coli, Faecalibacterium prausnitzii, and Lactobacillus spp.). Stimulation with prebiotics caused changes in the abundance of bacteria especially Lactobacillus spp. and Bifidobacterium spp. in the cecum. The abundance of both genera increased in each study group compared to the control group. The highest abundance of Bifidobacterium spp. in the ileum was found in the MOS3 group compared to the control group. There were changes in the XOS4 and MOS3 groups in the expression of: FFAR4, GLUT1, AvBD1, CATHL2, IL-2, IL-12, and IL-17 in the caecum. In conclusion, in ovo administration of prebiotics increased intestinal colonization by bacteria. The prebiotics influenced gene expression levels via changes in the gut microbiota.

The end of toxoid vaccine development for preventing Clostridioides difficile infections?

The end of toxoid vaccine development for preventing Clostridioides difficile infections?

PUNCH CD3-OLS: a phase 3 prospective observational cohort study to evaluate the safety and efficacy of fecal microbiota, live-jslm (REBYOTA) in adults with recurrent Clostridioides difficile infection.

To evaluate the safety and efficacy of fecal microbiota, live-jslm (RBL; REBYOTA) - the first single-dose, broad consortia microbiota-based live biotherapeutic approved by the United States (US) Food and Drug Administration for preventing recurrent Clostridioides difficile infection (rCDI) in adults following standard-of-care (SOC) antibiotic treatment. PUNCH CD3-OLS was a prospective, phase 3, open-label study, conducted across the US and Canada. Participants were aged ≥18 years with documented rCDI and confirmed use of SOC antibiotics. Participants with comorbidities including inflammatory bowel disease and mild-to-moderate immunocompromising conditions could be enrolled. A single dose of RBL was rectally administered within 24-72h of antibiotic completion. The primary endpoint was the number of participants with RBL- or administration-related treatment-emergent adverse events (TEAEs). Secondary endpoints included treatment success and sustained clinical response, at 8 weeks and 6 months after RBL administration, respectively. Overall, 793 participants were enrolled, of whom 697 received RBL. TEAEs through 8 weeks after administration were reported by 47.3% of participants; most events were mild or moderate gastrointestinal disorders. Serious TEAEs were reported by 3.9% of participants. The treatment success rate at 8 weeks was 73.8%; in participants who achieved treatment success, the sustained clinical response rate at 6 months was 91.0%. Safety and efficacy rates were similar across demographic and baseline characteristic subgroups. RBL was safe and efficacious in participants with rCDI and common comorbidities. This is the largest microbiota-based live biotherapeutic study to date and findings support use of RBL to prevent rCDI in a broad patient population. The study is registered at ClinicalTrials.gov (NCT03931941).

Validation of Lyophilized Human Fecal Microbiota for the Treatment of Clostridioides difficile Infection: A Pilot Study with Pharmacoeconomic Analysis of a Middle-Income Country-Promicrobioma Project.

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. 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. 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. 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.

Microbiome and Metabolome Restoration After Administration of Fecal Microbiota, Live-jslm (REBYOTA®) for Preventing Recurrent Clostridioides difficile Infection.

Microbiota-based treatments are effective in preventing recurrent Clostridioides difficile infection (rCDI). Fecal microbiota, live-jslm (REBYOTA®; RBL, previously RBX2660) was shown to prevent rCDI in a phase 3, randomized, double-blinded placebo controlled clinical trial (PUNCH™ CD3). Stool samples from participants in PUNCH™ CD3 who received a single blinded dose of rectally administered RBL or placebo were sequenced to determine microbial community composition and calculate the Microbiome Health Index for post-antibiotic dysbiosis (MHI-A). The composition of bile acids (BAs) in the same samples was quantified by liquid chromatography mass spectrometry. Relationships between BA composition and microbiota community structure and correlations with treatment outcomes were assessed. Before administration, Gammaproteobacteria and Bacilli dominated the microbiota community and primary BAs were more prevalent than secondary BAs. Clinical success after administration correlated with shifts to predominantly Bacteroidia and Clostridia, a significant increase in MHI-A, and a shift from primary to secondary BAs. Several microbiota and BA changes were more extensive in RBL-treated responders compared to placebo-treated responders, and microbiota changes correlated with BA changes. Clinical response and RBL administration were associated with significant restoration of microbiota and BA composition. NCT03244644.

Evaluating the antibacterial, antibiofilm, and anti-toxigenic effects of postbiotics from lactic acid bacteria on Clostridium difficile.

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. 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. 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). 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.

The Incidence of Clostridioides difficile Infection in the Post-COVID-19 Era in a Hospital in Northern Greece.

Clostridioides difficile infection (CDI) has evolved to be the most significant cause of healthcare-associated diarrhoea and one of the leading representatives of healthcare-associated infections, with a high associated mortality. The aim of this retrospective study was to record the incidence rates and the epidemiological and clinical features of CDI in a large tertiary hospital of northern Greece in the years 2022-2023. All patients with CDI-compatible symptomatology and a positive CDI diagnostic test (GDH-glutamate dehydrogenase and toxin-positive FIA-Fluorescent Immuno-chromatography-SD Biosensor, and/or film array) were included (104 from a total of 4560 admitted patients). Their demographic, laboratory, and clinical data were recorded and analysed. The incidence of CDI in admitted patients was found to be higher than previous reports in the geographical area, reaching 54.6/10,000 patient days and following a rising trend over the course of the study. Thirty-day mortality was high (39.4%), potentially related to new emerging hypervirulent C. difficile strains. In view of the high prevalence of multidrug-resistant organisms in the region, and the significant mortality associated with this infection, these findings particularly point to the need for the implementation of organized surveillance and infection prevention protocols.

Potential effectiveness of parenteral nemonoxacin in the treatment of Clostridioides difficile infections: in vitro, ex vivo, and mouse studies.

Antimicrobial therapy plays a crucial role in the management of CDI patients. However, the standard agent for treating CDIs is limited to oral fidaxomicin or vancomycin. For patients made nil by mouth, there is a clinically urgent and essential need to develop an intravenous antibiotic. For C. difficile with the lowest MIC of nemonoxacin and vancomycin, the inhibitory effects were tested using the kinetic time-kill assay and ex vivo co-culture model. The effectiveness of nemonoxacin and vancomycin in inhibiting spore germination, the sporicidal activity, and the treatment of mice with CDIs were compared. For clinical isolates and laboratory strains, lower MICs of nemonoxacin against C. difficile than levofloxacin and ciprofloxacin were observed, even in those harboring point mutations in the quinolone-resistance determining region. Although nemonoxacin failed to suppress spore outgrowth and germination in C. difficile, it exhibited an effective inhibitory effect against C. difficile in the kinetic time-kill assay and the ex vivo co-culture model. Mice receiving intraperitoneal nemonoxacin had less weight loss, higher cecum weight, a longer colon length, and lower expression of the tcdB gene, compared with untreated mice. Notably, there were no significant differences observed in weight loss, cecum weight, colon length, or tcdB gene expression between mice treated with vancomycin and those treated with any dose of nemonoxacin. Similarly, no significant differences were found between mice receiving combination therapy of intraperitoneal nemonoxacin plus oral vancomycin and those treated with intraperitoneal nemonoxacin or oral vancomycin alone. The potential role of nemonoxacin, which can be administered parenterally, for treating CDIs was evidenced through the in vitro, ex vivo, and mouse models.

Chemical optimization and derivatization of micrococcin p2 to target multiple bacterial infections: new antibiotics from thiopeptides.

Antimicrobial resistance poses a significant threat to humanity, and the development of new antibiotics is urgently needed. Our research has focused on thiopeptide antibiotics such as micrococcin P2 (MP2) and derivatives thereof as new anti-infective agents. Thiopeptides are sulfur-rich, structurally complex substances that exhibit potent activity against Gram-positive pathogens and Mycobacteria species, including clinically resistant strains. The clinical development of thiopeptides has been hampered by the lack of efficient synthetic platforms to conduct detailed structure-activity relationship studies of these natural products. The present contribution touches upon efficient synthetic routes to MP2 that laid the groundwork for clinical translation. The medicinal chemistry campaign on MP2 has been guided by computational molecular dynamic simulations and parallel investigations to improve drug-like properties, such as enhancing the aqueous solubility and optimizing antibacterial activity. Such endeavors have enabled identification of promising lead compounds, AJ-037 and AJ-206, against Mycobacterium avium complex (MAC). Extensive in vitro studies revealed that these compounds exert potent activity against MAC species, a subspecies of non-tuberculous mycobacteria (NTM) that proliferate inside macrophages. Two additional pre-clinical candidates have been identified: AJ-024, for the treatment of Clostridioides difficile infections, and AJ-147, for methicillin-resistant Staphylococcus aureus impetigo. Both compounds compare quite favorably with current first-line treatments. In particular, the ability of AJ-147 to downregulate pro-inflammatory cytokines adds a valuable dimension to its clinical use. In light of above, these new thiopeptide derivatives are well-poised for further clinical development.

Best Practices in the Management of Clostridioides difficile Infection in Developing Nations.

Clostridioides difficile infection (CDI) is a well-known cause of hospital-acquired infectious diarrhea in developed countries, though it has not been a top priority in the healthcare policies of developing countries. In the last decade, several studies have reported a wide range of CDI rates between 1.3% and 96% in developing nations, raising the concern that this could represent a healthcare threat for these nations. This review defines developing countries as those with a human development index (HDI) below 0.8. We aim to report the available literature on CDI epidemiology, diagnostics, management, and prevention in developing countries. We identify limitations for CDI diagnosis and management, such as limited access to CDI tests and unavailable oral vancomycin formulation, and identify opportunities to enhance CDI care, such as increased molecular test capabilities and creative solutions for CDI. We also discuss infection prevention strategies, including antimicrobial stewardship programs and opportunities emerging from the COVID-19 pandemic, which could impact CDI care.

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

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

The global burden and trend of Clostridioides difficile and its association with world antibiotic consumption, 1990-2019.

To estimate the global trends and disease burden of Clostridioides difficile infection (CDI) and its correlation with worldwide antibiotic consumption. Clostridioides difficile infection and antibiotic consumption data were retrieved from the Global Burden of Disease 2019, ResistanceMap-AntibiocUse, Food and Drug Administration (FDA) Adverse Event Reporting System, and Global Antimicrobial Resistance and Use Surveillance System. Jointpoint regression and age-period-cohort model were developed to show the global trends and burden of CDI. Correlation tests were calculated to explore the relationship between CDI and antibiotics. Globally, CDI is the most significant one with a high-rocketing burden increase rate among 13 pathogens causing diarrheal deaths and disability-adjusted life years (DALYs). The age-standardised death rate (ASDR) increased from 0.19 in 1990 to 0.43 in 2019, in which the elderly and females are at higher risk. A rapid increase in ASDR in high to middle sociodemographic index (SDI) regions such as North America (average annual percentage change (AAPC) = 7.71%), Andean (AAPC = 7.82%), and Southern Latin America (AAPC = 11.08%) was identified. Antibiotic consumption has a significant positive correlation with CDI with different risk stratifications. The global burden of CDI has continuously increased for the past 30 years, especially in high to middle-SDI regions. World antibiotic consumption showed a strong positive correlation with CDI with different risk stratification. More effective prevention and control measures should be implemented in these critical regions, with a specific emphasis on vulnerable populations, to mitigate the spread of epidemics.

The Role of Fecal Microbiota Transplantation (FMT) in the Management of Metabolic Diseases in Humans: A Narrative Review.

The gut microbiota represents a complex ecosystem of trillions of microorganisms residing in the human gastrointestinal tract, which is known to interact with the host physiology and regulate multiple functions. Alterations in gut microbial composition, diversity, and function are referred to as dysbiosis. Dysbiosis has been associated with a variety of chronic diseases, including Clostridioides difficile infections, but also cardiometabolic diseases, including obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). The implication of gut microbiota dysbiosis in the pathogenesis of both obesity and T2DM has paved the way to implementing novel therapeutic approaches for metabolic diseases through gut microbial reconfiguration. These interventions include probiotics, prebiotics, and synbiotics, while a more innovative approach has been fecal microbiota transplantation (FMT). FMT is a procedure that delivers healthy human donor stool to another individual through the gastrointestinal tract, aiming to restore gut microbiota balance. Several studies have investigated this approach as a potential tool to mitigate the adverse metabolic effects of gut microbiota aberrations associated with obesity and T2DM. The aim of the present review was to critically summarize the existing evidence regarding the clinical applications of FMT in the management of obesity and T2DM and provide an update on the potential of this method to remodel the entire host microbiota, leading thus to weight loss and sustained metabolic benefits. Safety issues, long-term efficacy, limitations, and pitfalls associated with FMT studies are further discussed, emphasizing the need for further research and standardization in certain methodological aspects in order to optimize metabolic outcomes.

A diagnostic dilemma: cytomegalovirus colitis as an uncommon comorbidity in inflammatory bowel disease: a case report

BackgroundThe role of cytomegalovirus infection as an opportunistic pathogen in exacerbating ulcerative colitis and its response to treatment remain a topic of ongoing debate. Clinicians encounter numerous challenges, including the criteria for differentiating between an acute ulcerative colitis flare and true cytomegalovirus colitis, the diagnostic tests for identifying cytomegalovirus colitis, and determining the appropriate timing for initiating antiviral therapy.Case presentationA 28-year-old Syrian female with a seven-year history of pancolitis presented with worsening bloody diarrhea, abdominal pain, and tenesmus despite ongoing treatment with azathioprine, mesalazine, and prednisolone. She experienced a new flare of acute severe ulcerative colitis despite recently completing two induction doses of infliximab (5 mg/kg) initiated four weeks prior for moderate-to-severe ulcerative colitis. She had no prior surgical history. Her symptoms included watery, bloody diarrhea occurring nine to ten times per day, abdominal pain, and tenesmus. Initial laboratory tests indicated anemia, leukocytosis, elevated C-reactive protein (CRP) and fecal calprotectin levels, and positive CMV IgG. Stool cultures, Clostridium difficile toxin, testing for Escherichia coli and Cryptosporidium, and microscopy for ova and parasites were all negative. Sigmoidoscopy revealed numerous prominent erythematous area with spontaneous bleeding. Biopsies demonstrated CMV inclusions confirmed by immunohistochemistry, although prior biopsies were negative. We tapered prednisolone and azathioprine and initiated ganciclovir at 5 mg/kg for ten days, followed by valganciclovir at 450 mg twice daily for three weeks. After one month, she showed marked improvement, with CRP and fecal calprotectin levels returning to normal. She scored one point on the partial Mayo score. The third induction dose of infliximab was administered on schedule, and azathioprine was resumed.ConclusionConcurrent cytomegalovirus infection in patients with inflammatory bowel disease presents a significant clinical challenge due to its associated morbidity and mortality. Diagnosing and managing this condition is particularly difficult, especially regarding the initiation or continuation of immunosuppressive therapies.

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

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

Clostridioides difficile Infection: Use of Inflammatory Biomarkers and Hemogram-Derived Ratios to Predict Mortality Risk in Hospitalized Patients.

Clostridioides difficile infection (CDI) is a significant cause of mortality, especially in healthcare environments. Reliable biomarkers that can accurately predict mortality in CDI patients are yet to be evaluated. Our study aims to evaluate the accuracy of several inflammatory biomarkers and hemogram-derived ratios in predicting mortality in CDI patients, such as the neutrophil-to-lymphocyte ratio (NLR), the systemic immune-inflammation index (SII), the platelet-to-neutrophil ratio (PNR), the derived neutrophil-to-lymphocyte ratio (dNLR), C-reactive protein (CRP), the platelet-to-lymphocyte ratio (PLR), and procalcitonin (PCT). NLR showed a sensitivity of 72.5% and a specificity of 58.42% with an area under curve (AUC) = 0.652. SII had a sensitivity of 77.5%, a specificity of 54.74%, and an AUC = 0.64. PNR, neutrophils, dNLR, and lymphocytes had lower AUCs which ranged from 0.595 to 0.616, with varied sensitivity and specificity. CRP, leukocytes, and platelets showed modest predictive values with AUCs below 0.6. PCT had a sensitivity of 100%, a low specificity of 7.41%, and an AUC = 0.528. We conducted a retrospective analysis of CDI patients from two different hospital settings in Italy and Romania during the COVID-19 pandemic, from 1 January 2020 to 5 May 2023. Statistical analyses included t-tests, Wilcoxon rank-sum tests, χ2 tests, and multivariate logistic regression to identify predictors of mortality. ROC analysis assessed the accuracy of biomarkers and hemogram-derived ratios. A p value < 0.05 was considered significant. Neutrophils, dNLR, NLR, SII, and PNR are valuable biomarkers for predicting mortality in CDI patients. Understanding these predictors can improve risk stratification and clinical outcomes for CDI patients.

The Potential Therapeutic Effects of Botulinum Neurotoxins on Neoplastic Cells: A Comprehensive Review of In Vitro and In Vivo Studies.

A systematic review of the literature found fifteen articles on the effect of a botulinum toxin on neoplastic cell lines and eight articles on in vivo neoplasms. The reported in vitro effects rely on high doses or the mechanical disruption of cell membranes to introduce the botulinum neurotoxin into the cell cytoplasm. The potency of the botulinum neurotoxin to intoxicate non-neuronal cells (even cell lines expressing an appropriate protein receptor) is several orders of magnitude lower compared to that to intoxicate the primary neurons. The data suggest that the botulinum toxin disrupts the progression of cancer cells, with some studies reporting apoptotic effects. A majority of the data in the in vivo studies also showed similar results. No safety issues were disclosed in the in vivo studies. Limited studies have suggested similar anti-neoplastic potential for the clostridium difficile. New modes of delivery have been tested to enhance the in vivo delivery of the botulinum toxin to neoplastic cells. Careful controlled studies are necessary to demonstrate the efficacy and safety of this mode of anti-neoplastic treatment in humans.

Graft-versus-host disease in patients with bone marrow transplants: A retrospective study analyzing outcomes and healthcare burden in US hospitals.

Graft-versus-host disease (GVHD) is a recognized complication among individuals undergoing bone marrow transplantation (BMT). There is a requirement for supplementary data regarding the in-patient outcomes of GVHD in individuals who have undergone BMT. Our analysis seeks to assess the healthcare burden and outcomes associated with GVHD in hospitalized patients who have undergone BMT. In this retrospective study, we used data from the National Inpatient Sample (NIS) database spanning from 2016 to 2019. Utilizing ICD-10 codes, we distinguished hospitalizations related to BMT and grouped them into two categories: those with GVHD and those without GVHD. Our areas of focus included in-hospital mortality, length of stay, charges, and associations related to GVHD. Unadjusted odds ratios/coefficients were computed through univariable analysis, followed by adjusted odds ratios (aORs)/coefficients from multivariable analysis that considered potential confounding factors. From 2016 to 2019, data were collected from 13,999 hospitalizations with bone marrow transplants. Among them, 836 had GVHD cases. Patient characteristics showed slight differences in mean age and demographics between the two groups, with GVHD patients having a mean age of 51.61 years and higher percentages of males and whites. Analyzing outcomes, patients with GVHD experienced significantly longer hospital stays (41.4 days vs. 21.3 days) and higher total hospital charges ($824,058 vs. $335,765). Adjusting for confounding factors, GVHD posed a substantial risk. The aOR for mortality in GVHD hospitalizations was 7.20 (95% CI: 5.54-9.36, p < .001). The coefficient for the length of stay was 19.36 days (95% CI: 17.29-21.42, p < .001), and the coefficient for total hospital charges was $453,733 (95% CI: $396,577 to $510,889, p < .001) in GVHD cases. Furthermore, GVHD in patients was associated with elevated risks of various medical conditions. The aORs for sepsis, pneumonia, acute respiratory failure, intubation and mechanical ventilation, Clostridium difficile infection, and acute kidney injury (AKI) in GVHD patients were 2.79 (95% CI: 2.28-3.41, p < .001), 3.30 (95% CI: 2.57-4.24, p < .001), 5.10 (95% CI: 4.01-6.49, p < .001), 4.88 (95% CI: 3.75-6.34, p < .001), 1.45 (95% CI: 1.13-1.86, p = .003), and 3.57 (95% CI: 2.97-4.29, p < .001). GVHD in individuals undergoing BMT is linked to elevated mortality rates, prolonged hospitalization, and higher healthcare costs. Moreover, they face a significantly increased risk of developing complications, such as sepsis, pneumonia, acute respiratory failure, C. difficile infection, and AKI. These results underscore the critical need for vigilant monitoring and effective GVHD management to improve patient outcomes and reduce the complications associated with BMT. Nevertheless, further prospective studies are essential to obtain a more profound understanding and a comprehensive assessment of outcomes in these hospitalized patients.

Efficacy of fidaxomicin versus vancomycin in the treatment of Clostridium difficile infection: A systematic meta-analysis.

To compare the efficacy, recurrence rate, adverse event rate and mortality of fidaxomicin compared with vancomycin in treating different types of Clostridium difficile infection (CDI). A systematic search was conducted on PubMed, Embase, Web of Science, Cochrane Library and clinical trial registration databases for research on fidaxomicin versus vancomycin in the treatment of CDI and the retrieval period extended from the establishment of the database to July 22, 2022. A total of 15 studies were included, including 8 RCTs and 7 retrospective cohort studies. Results showed that there was no significant difference in the overall efficacy of the treatment between fidaxomicin and vancomycin, and results in the subgroups of CDI hypervirulent strains and recurrent CDI were obtained, but vancomycin was more effective than fidaxomicin in the treatment of severe CDI (RR = 0.94, 95% CI: 0.90-0.98, P < .01). Results showed that fidaxomicin is superior to vancomycin in terms of 40-day recurrence rate (RR = 0.52, 95% CI: 0.38-0.70, P < .01), 60-day recurrence rate (RR = 0.38, 95% CI: 0.21-0.69, P < .01) and 90-day recurrence rate (RR = 0.62, 95% CI: 0.50-0.77, P < .01). For the recurrence rate of the treatment in CDI hypervirulent strains, severe CDI and recurrent CDI, there was no significant difference between the 2 groups. In addition, there was no significant difference in the incidence of clinical adverse reactions, and same outcomes appeared in all-cause mortality at 40-day, severe CDI and recurrent CDI, but fidaxomicin was superior to vancomycin in all-cause mortality over 60-day (RR = 0.57, 95% CI: 0.34-0.96, P = .03). There were no significant differences between fidaxomicin and vancomycin in the treatment of CDI in therapeutic effectiveness and adverse reactions, while fidaxomicin was superior to vancomycin in terms of recurrence rate and long-term mortality, and vancomycin is more effective in treating severe CDI.