Asymptomatic carriers significantly influence the transmission dynamics of C. difficile. This study aimed to assess the prevalence of toxigenic C. difficile asymptomatic colonization (tCDAC) and investigate its heterogeneity across different populations. We searched MEDLINE, Web of Science, and Scopus for articles published between 2000 and 2023 on tCDAC. Studies including asymptomatic adults with laboratory-confirmed tCDAC were eligible. We performed a random-effects meta-analysis to estimate the pooled prevalence by clinical characteristics, settings, and geographic areas. In addition, we used outlier analyses and meta-regression to explore sources of prevalence variability.

Fifty-one studies involving 39,447 patients were included. The tCDAC prevalence ranged from 0.5 to 51.5%. Among pooled estimates, a high prevalence was observed in patients with cystic fibrosis, outbreak settings, and cancer patients, whereas the lowest rates were found in healthy individuals and healthcare workers. Similar colonization rates were observed between admitted and hospitalized patients. Our meta-regression analysis revealed lower rates in healthy individuals and higher rates in cystic fibrosis patients and studies from North America. Additionally, compared with that among healthy individuals, the prevalence significantly increased by 15-47% among different populations and settings.

Our study revealed that tCDAC is a common phenomenon. We found high prevalence estimates that showed significant variability across populations. This heterogeneity could be partially explained by population characteristics and settings, supporting their role in the pathogenesis and burden of this disease. This highlights the need to identify high-risk groups to improve infection control strategies, decrease transmission dynamics, and better understand the natural history of this disease.

The impact of antibiotics on the gut microbiota in kidney transplant recipients is not well characterized. In this study, we determine the impact of different subclasses of antibiotics on the gut microbiota in a cohort of 168 kidney transplant recipients.

Gut microbiome profiling was performed on 510 fecal specimens using 16S rRNA gene sequencing of the V4-V5 hypervariable region. We classified fecal specimens by antibiotic exposure into 5 categories: Beta-lactam, Fluoroquinolone (FQ), Beta-lactam & FQ Group, Other Antibiotics, and No Antibiotic (No Abx). Mixed-effects regression models were utilized to identify changes in microbial diversity and in the centered log-ratio (CLR) transformed abundance of genera while adjusting for important covariates.

Antibiotic administration was associated with a significant decrease in the Shannon alpha diversity index, a decreased abundance of 11 taxa including Eubacterium and Ruminococcus, and an increased abundance of 16 taxa including Enterococcus and Staphylococcus. Exposure to Beta-lactam antibiotics was associated with an increased abundance of 10 taxa including Enterococcus and a decreased abundance of 5 taxa including Eubacterium while exposure to FQ antibiotics was associated with an increased abundance of 3 taxa and a decreased abundance of 4 taxa including Ruminococcus.

Beta-lactam antibiotics and FQ antibiotics have a profound impact on the gut microbiota in kidney transplant recipients. Given the link of the gut microbiota to infectious complications, antibiotic associated changes in the microbiota may lead to an increased risk for further infections.

Kidney transplantation is an effective way to improve the condition of patients with end-stage renal disease. However, maintaining long-term graft function and improving patient survival remain a key challenge after kidney transplantation. Dysbiosis of intestinal flora has been reported to be associated with complications in renal transplant recipients. The commensal microbiota plays an important role in the immunomodulation of the transplant recipient responses. However, several processes, such as the use of perioperative antibiotics and high-dose immunosuppressants in renal transplant recipients, can lead to gut dysbiosis and disrupt the interaction between the microbiota and the host immune responses, which in turn can lead to complications such as infection and rejection in organ recipients. In this review, we summarize and discuss the changes in intestinal flora and their influencing factors in patients after renal transplantation as well as the evidence related to the impact of intestinal dysbiosis on the prognosis of renal transplantation from in vivo and clinical studies, and conclude with a discussion of the use of microbial therapy in the transplant population. Hopefully, a deeper understanding of the function and composition of the microbiota in patients after renal transplantation may assist in the development of clinical strategies to restore a normal microbiota and facilitate the clinical management of grafts in the future.

Clostridioides difficile infection (CDI) is a significant cause of morbidity and mortality among hospitalized patients, particularly those who are immunosuppressed. We aim to assess the outcomes of CDI among kidney transplant (KT) recipients.

Nationwide Inpatient Sample from 2016 to 2020 was used to identify patients with KT and stratify based on the presence of CDI. Data were collected regarding demographics and comorbidities. Outcomes included in-hospital mortality, acute kidney injury, intensive care unit admission, transplant rejection, transplant failure, length of stay, and total hospitalization charges. The relationships between variables of interest and outcomes were analyzed using multivariate regression.

A total of 557,635 KT recipients were included. CDI prevalence was 2.4%. The majority of patients in the CDI group were age >65 (43.6%), female (51%), White (55.3%), and had Medicare insurance (74.9%). On multivariate regression analysis, CDI was associated with increased odds of acute kidney injury (aOR 2.06, p < 0.001), intensive care unit admission (aOR 2.47, p < 0.001), and mortality (aOR 1.90, p < 0.001). CDI was also associated with longer length of stay (9.35 days vs 5.42 days, p < 0.001) and higher total hospitalization charges ($110,063 vs $100,006, p < 0.001). There was no difference in transplant rejection, complication, failure, or infection among KT recipients with CDI and those without.

We found that CDI was associated with worse outcomes and higher costs. KT patients should be monitored closely for signs of CDI in order to initiate appropriate management.

Kidney transplant often is complicated by infections in the recipient from therapy-related and patient-related risk factors. Infections in kidney transplant recipients are associated with increased morbidity, mortality, and allograft dysfunction. There is a predictable timeline after kidney transplant regarding the types of pathogens causing infections, reflecting the net state of immunosuppression. In the early post-transplant period, bacterial infections comprise two thirds of all infections, followed by viral and fungal infections. Infections occurring early after kidney transplantation are generally the result of postoperative complications. In most cases, opportunistic infections occur within 6 months after kidney transplantation. They may be caused by a new infection, a donor-derived infection, or reactivation of a latent infection. Community-acquired pneumonia, upper respiratory tract infections, urinary tract infections, and gastrointestinal infections are the most common infections in the late period after transplantation when the net immunosuppression is minimal. It is crucial to seek information on the time after transplant, reflecting the net state of immunosuppression, previous history of exposure/infections, geography, and seasonal outbreaks. It is imperative that we develop regionally specific guidelines on screening, prevention, and management of infections after kidney transplantation.

Kidney transplantation is an effective method to improve the condition of patients with end-stage renal disease. The gut microbiota significantly affects the immune system and can be used as an influencing factor to change the prognoses of patients who have undergone kidney transplantation. Recipients after kidney transplantation showed a lower abundance of Firmicutes and Faecalibacterium prausnitzii and a higher proportion of Bacteroidetes and Proteobacteria. After using prebiotics, synbiotics, and fecal microbiota transplantation to regulate the microbial community, the prognoses of patients who underwent kidney transplantation evidently improved. We aimed to determine the relationship between gut microbiota and various postoperative complications inpatients who have undergone kidney transplantation in recent years and to explore how gut microecology affects post-transplant complications. An in-depth understanding of the specific functions of gut microbiota and identification of the actual pathogenic flora during complications in patients undergoing kidney transplantation can help physicians develop strategies to restore the normal intestinal microbiome of transplant patients to maximize their survival and improve their quality of life.

The last decade has seen an explosion of advanced assays for the diagnosis of infectious diseases, yet evidence-based recommendations to inform their optimal use in the care of transplant recipients are lacking. A consensus conference sponsored by the American Society of Transplantation (AST) was convened on December 7, 2021, to define the utility of novel infectious disease diagnostics in organ transplant recipients. The conference represented a collaborative effort by experts in transplant infectious diseases, diagnostic stewardship, and clinical microbiology from centers across North America to evaluate current uses, unmet needs, and future directions for assays in 5 categories including (1) multiplex molecular assays, (2) rapid antimicrobial resistance detection methods, (3) pathogen-specific T-cell reactivity assays, (4) next-generation sequencing assays, and (5) mass spectrometry-based assays. Participants reviewed and appraised available literature, determined assay advantages and limitations, developed best practice guidance largely based on expert opinion for clinical use, and identified areas of future investigation in the setting of transplantation. In addition, attendees emphasized the need for well-designed studies to generate high-quality evidence needed to guide care, identified regulatory and financial barriers, and discussed the role of regulatory agencies in facilitating research and implementation of these assays. Findings and consensus statements are presented.

The microbiota plays an important role in health and disease. During organ transplantation, perturbations in microbiota influence transplant outcome. We review recent advances in characterizing microbiota and studies on regulation of intestinal epithelial barrier function and mucosal and systemic immunity by microbiota and their metabolites. We discuss implications of these interactions on transplant outcomes.

Metagenomic approaches have helped the research community identify beneficial and harmful organisms. Microbiota regulates intestinal epithelial functions. Signals released by epithelial cells or microbiota trigger pro-inflammatory or anti-inflammatory effects on innate and adaptive immune cells, influencing the structure and function of the immune system. Assessment and manipulation of microbiota can be used for biomarkers for diagnosis, prognosis, and therapy.

The bidirectional dialogue between the microbiota and immune system is a major influence on immunity. It can be targeted for biomarkers or therapy. Recent studies highlight a close association of transplant outcomes with microbiota, suggesting exciting potential avenues for management of host physiology and organ transplantation.

Kidney transplantation is recognized as one of the most effective treatments for patients who suffer from end-stage renal disease. The major potential outcomes following kidney transplantation include engraftment, rejection, and associated complications. The outcomes are dependent on a variety of factors in those who underwent renal grafts or kidney transplant recipients. Those factors include the administration of immunosuppressive drugs and prophylactic antimicrobial agents to recipients. Recent studies have shown that gut microbiota play an important role in the outcome of subjects with kidney transplantation. An imbalance of the components/diversity of gut microbiota, known as gut dysbiosis, has been shown to have a big impact on the immune system of the host and the modification of host inflammatory cytokines. Although gut dysbiosis is affected by variation in diet and medication, a substantial amount of evidence showing a link between alteration in human gut microbiota and outcomes of kidney transplantation has recently been reported. Therefore, the objective of this review is to comprehensively summarize and discuss the major findings from in vivo and clinical data pertaining to the impact of gut microbiota on kidney transplantation. Any controversial findings are compiled to enable a clear overview of the role of gut microbiota and the outcome of kidney transplantation.

Infectious diarrhea following hematopoietic cell transplantation (HCT) significantly contributes to morbidity and mortality. Most HCT recipients experience diarrhea in the post-transplantation period, and infectious pathogens are frequently detected during diarrheal episodes. However, little is known about how frequently these patients are colonized with gastrointestinal (GI) pathogens before their transplantation and whether colonization predicts future diarrheal illness. We sought to determine how frequently HCT recipients are colonized with GI pathogens before HCT and the degree to which pre-HCT colonization predicts post-transplantation infectious diarrheal illness. We conducted a prospective cohort study of allogeneic and autologous HCT recipients at a single center between December 2016 and January 2019. Stool samples were collected during the week before HCT, and formed samples were evaluated for the presence of 22 diarrheal pathogens using the BioFire FilmArray GI panel. We determined the frequency with which participants were colonized with each pathogen and identified factors associated with colonization. We then determined how frequently pretransplantation colonization led to post-transplantation diarrheal infections due to the colonizing pathogen and whether colonization was associated with increased number of days of post-transplantation diarrhea during the transplant hospitalization. We enrolled 112 asymptomatic patients (allogeneic, 61%; autologous, 39%) who had a formed stool specimen before HCT, of whom 41 (37%) had a GI pathogen detected. The most commonly detected organisms were Clostridioides difficile (n = 21; 19%), Yersinia enterocolitica (n = 9; 8%), enteropathogenic Escherichia coli (EPEC) (n = 6; 6%), and norovirus (n = 5; 4%). Female sex and previous C. difficile infection were associated with C. difficile colonization, and having non-Hodgkin lymphoma was associated with being colonized with a diarrheal pathogen other than C. difficile. Thirteen of 21 patients (62%) with pretransplantation C. difficile colonization developed a clinical C. difficile infection post-transplantation, and 8 of 10 patients (80%) colonized with EPEC or enteroaggregative E. coli developed post-transplantation infections due to their colonizing pathogen. Pretransplantation C. difficile colonization was also associated with an increased duration of post-transplantation diarrhea (P = .048). Conversely, none of the 9 patients with pretransplantation Yersinia enterocolitica colonization developed a post-transplantation Y. enterocolitica infection. Patients admitted for HCT are frequently colonized with a diverse range of GI pathogens. Colonization with C. difficile colonization and diarrheagenic E. coli is frequently associated with post-transplantation diarrheal infections caused by these organisms, but the clinical significance of colonization with other GI pathogens is not clear.

Post-transplant diarrhea is a common complication after solid organ transplantation and is frequently attributed to the widely prescribed immunosuppressant mycophenolate mofetil (MMF). Given recent work identifying the relationship between MMF toxicity and gut bacterial β-glucuronidase activity, we evaluated the relationship between gut microbiota composition, fecal β-glucuronidase activity, and post-transplant diarrhea. We recruited 97 kidney transplant recipients and profiled the gut microbiota in 273 fecal specimens using 16S rRNA gene sequencing. We further characterized fecal β-glucuronidase activity in a subset of this cohort. Kidney transplant recipients with post-transplant diarrhea had decreased gut microbial diversity and decreased relative gut abundances of 12 genera when compared to those without post-transplant diarrhea (adjusted p value < .15, Wilcoxon rank sum test). Among the kidney transplant recipients with post-transplant diarrhea, those with higher fecal β-glucuronidase activity had a more prolonged course of diarrhea (≥7 days) compared to patients with lower fecal β-glucuronidase activity (91% vs 40%, p = .02, Fisher's exact test). Our data reveal post-transplant diarrhea as a complex phenomenon with decreased gut microbial diversity and commensal gut organisms. This study further links commensal bacterial metabolism with an important clinical outcome measure, suggesting fecal β-glucuronidase activity could be a novel biomarker for gastrointestinal-related MMF toxicity.

Diarrhea is one of the common gastrointestinal (GI) adverse events after solid organ transplantation. Diarrhea may be caused by infectious or non-infectious etiology. The infectious etiology of diarrhea varies according to the location and duration of diarrhea. Non-infectious etiologies include drugs, inflammatory bowel disease, neoplasia. The objective of this study was to evaluate the etiological profile of diarrhea in solid organ transplant recipients presenting to a tertiary care center in Southern India.

This was a retrospective analysis of prospectively collected data of all solid organ transplantation recipients referred to the Department of Medical Gastroenterology for evaluation of diarrhea from April 2012 till May 2014. All patients had stool evaluated by wet mount examination, modified acid fast (AFB) stain, trichrome stain, culture, and Clostridium difficile toxin assay. EDTA plasma was collected for quantitative Cytomegalovirus (CMV) detection by real-time PCR. If the diarrhea was acute (<2 wk), and no etiological agent was identified, empirical antibiotic therapy was instituted and followed up. If persistent or chronic diarrhea (>2-4 wk), endoscopic evaluation (upper GI endoscopy and/or colonoscopy with biopsies), depending on the clinical type of diarrhea was done. If no specific etiological diagnosis was established after endoscopic evaluation, breath test for SIBO and celiac serology were done. If no specific etiology was identified after the above investigations, dose of immunosuppressive drugs was reduced. If diarrhea responded to dose reduction, it was considered to be drug related.

Fifty-eight episodes of diarrhea occurred in 55 solid organ transplant recipients during the study period. Renal transplant recipients constituted the majority (70%). Most (79%) of patients included in the study had their transplant > 6 mo ago. Infective diarrhea was the etiology in 46%, drug-related diarrhea in 29.3%. No specific etiology was identified in 22.4% of patients. Parasites accounted for 69% of all infective diarrhea. Stool evaluation was the main investigation in establishing diagnosis in acute diarrhea. Endoscopic evaluation was required in two thirds of patients to establish diagnosis in chronic diarrhea.

GI infections and drug-related diarrhea were the common causes of diarrhea in solid organ transplant recipients. Parasites were the most common infectious etiology of diarrhea. Step-wise evaluation was able to identify the etiology in ~ 77% of patients. Overall, 98% of diarrheal episodes resolved.

Background: Gut microbial diversity and composition play important roles in health. This cross-sectional study was designed to test the hypothesis that hospitalized children who may be relatively immunocompromised (IC), defined as those with cancer, sickle cell disease (SCD), transplantation, or receiving immunosuppressive therapy) would have decreased microbial diversity, increased Clostridioides difficile colonization and different species composition compared to non-immunocompromised (Non-IC) children admitted to the same pediatric unit. Methods: A stool sample was obtained within 72 h of admission to a single unit at The Children's Hospital at Montefiore, Bronx, NY from March 2016 to February 2017 and the microbiome assessed by 16S rRNA sequencing. C. difficile colonization was assessed by glutamate dehydrogenase antigen and toxin polymerase chain reaction assays. Results: Stool samples were obtained from 69 IC (32 SCD, 19 cancer, 9 transplantation and 9 other) and 37 Non-IC patients. There were no significant differences in microbial alpha diversity and C. difficile colonization comparing IC vs. non-IC patients. Lower alpha diversity, however, was independently associated with the use of proton pump inhibitors or antibiotics, including prophylactic penicillin in patients with SCD. Differences in specific species abundances were observed when comparing IC vs. non-IC patients, particularly children with SCD. Non-IC patients had increased abundance of commensals associated with health including Alistipes putredinis, Alistipes ihumii, Roseburia inulinivorans, Roseburia intestinalis, and Ruminococcus albus (p < 0.005). Conclusions: Antibiotics and proton pump inhibitors, which were more commonly used in IC children, were identified as risk factors for lower microbial diversity. Non-IC patients had higher abundance of several bacterial species associated with health. Longitudinal studies are needed to determine the clinical significance of these differences in gut microbiome.