Offline Two-Dimensional Liquid Chromatography-Mass Spectrometry for Deep Annotation of the Fecal Metabolome Following Fecal Microbiota Transplantation.

Biological interpretation of untargeted LC-MS-based metabolomics data depends on accurate compound identification, but current techniques fall short of identifying most features that can be detected. The human fecal metabolome is complex, variable, incompletely annotated, and serves as an ideal matrix to evaluate novel compound identification methods. We devised an experimental strategy for compound annotation using multidimensional chromatography and semiautomated feature alignment and applied these methods to study the fecal metabolome in the context of fecal microbiota transplantation (FMT) for recurrent C. difficile infection. Pooled fecal samples were fractionated using semipreparative liquid chromatography and analyzed by an orthogonal LC-MS/MS method. The resulting spectra were searched against commercial, public, and local spectral libraries, and annotations were vetted using retention time alignment and prediction. Multidimensional chromatography yielded more than a 2-fold improvement in identified compounds compared to conventional LC-MS/MS and successfully identified several rare and previously unreported compounds, including novel fatty-acid conjugated bile acid species. Using an automated software-based feature alignment strategy, most metabolites identified by the new approach could be matched to features that were detected but not identified in single-dimensional LC-MS/MS data. Overall, our approach represents a powerful strategy to enhance compound identification and biological insight from untargeted metabolomics data.

Antimicrobial prophylaxis and the rate of blood stream infections and Clostridioides difficile in pediatric stem cell transplantation: A single-center retrospective study.

BACKGROUND: The use of prophylactic antibiotics in the pre-engraftment period to minimize the risk of bacteremia is debatable given concerns of Clostridioides difficile (C. diff), antibiotics resistance, and disruption of gut microbiota. METHODS: We retrospectively reviewed the rate and characteristics of bacteremia and C. diff infections within the first 100 days post-HSCT in all pediatric patients who received routine antibacterial prophylaxis during HSCT from 2015 to 2018. C. diff infection was defined by the presence of three or more unformed stools in 24 h and positive stool test for C. diff or its toxins. RESULTS: One hundred and thirty-five (100 allogeneic and 35 autologous) transplants in 123 patients were eligible for analysis. Median age at transplant was 7.1 (range 0.2-13.7), 67 (55%) were women, and diagnosis was malignant condition in 68 patients. Median time to neutrophil engraftment was 18 days (13-23). Cefepime or piperacillin-tazobactam prophylaxis was used in 105 (78%) and 28 (21%) of patients, respectively. Only five (3%) patients had bacteremia during the pre-engraftment period, and 13 (11%) patients developed bacteremia postengraftment. Septic shock was present in only one patient pre-engraftment and was due to gram-negative bacteria. All patients who developed bacteremia received MAC. Thirteen patients (10%) of patients fulfilled C. diff infection definition. There was no mortality related to bacterial infections among our patients. CONCLUSIONS: The use of antibiotic prophylaxis was associated with low rate of bacteremia in the pre-engraftment period and a 10% risk of C. diff infections. More studies are needed to better evaluate the efficacy of antibiotic prophylaxis in HSCT patients.

First Clostridioides difficile Recurrence Is Highest Following Concomitant Antimicrobial Administration During and Within 30 Days of Treatment.

BACKGROUND: Clostridioides difficile infection (CDI) is an epidemic with the strongest risk factor being antibiotic usage. Patients who get CDI frequently require concomitant antibiotics for other indications around the time of their infection. AIMS: To assess the recurrence of CDI (rCDI) in patients receiving concomitant antibiotics at the same time or shortly thereafter treatment of CDI. METHODS: We retrospectively reviewed records for patients with their first inpatient CDI episode. Patients were grouped into those who didn't receive concomitant antibiotics (noABx), those receiving antibiotics at the same time as treatment of CDI (ABxDURING), those receiving antibiotics within 30-days of completion of CDI therapy (ABxAFTER) and those who received antibiotics both during and after CDI treatment (ABxDuringAfter). Our primary outcome was recurrence within 14-90 days; other outcomes included ICU stay at the time of diagnosis, 30-day ICU transfer, 30-day colectomy, and readmission. RESULTS: 457 patients had CDI during admission (mean age: 66.4 years, 51.9% female). 64.1% were exposed to concomitant antibiotics. Recurrence rates were 4.3%, 6.1%, 13.8% and 19.1%, for noABx, ABxDURING, ABxAFTER and ABxDuringAfter, respectively. Patients with ABxDuringAfter had the highest rates of rCDI when compared to noABx [OR 5.67, 95% CI (2.18-14.72)]. CONCLUSIONS: There is a high rate of utilization of non-CDI antibiotics during or shortly after completing CDI treatment with high rates of recurrence within 90-days. Concomitant antimicrobials alter the opportunity for the microbiota to re-grow and worsens dysbiosis leading to increases in recurrence. Concomitant antimicrobial stewardship remains important in patients being treated for CDI and shortly after treatment.

Detection of Clostridioides difficile in hospital environment by using C diff Banana Broth™.

116 environmental samples from a 504 bed clinical hospital obtained in 2017/19 were inoculated into C diff Banana Broth™. Six C. difficile and 12 C. pefringens strains were isolated. Antibiotic-resistant Clostridium spp. dominated in hospital environment. To determine Clostridium spp. in hospital environment suitable medium like C diff Banana Broth™ should be used.

TcdB of Clostridioides difficile Mediates RAS-Dependent Necrosis in Epithelial Cells.

A Clostridioides difficile infection (CDI) is the most common nosocomial infection worldwide. The main virulence factors of pathogenic C. difficile are TcdA and TcdB, which inhibit small Rho-GTPases. The inhibition of small Rho-GTPases leads to the so-called cytopathic effect, a reorganization of the actin cytoskeleton, an impairment of the colon epithelium barrier function and inflammation. Additionally, TcdB induces a necrotic cell death termed pyknosis in vitro independently from its glucosyltransferases, which are characterized by chromatin condensation and ROS production. To understand the underlying mechanism of this pyknotic effect, we conducted a large-scale phosphoproteomic study. We included the analysis of alterations in the phosphoproteome after treatment with TcdA, which was investigated for the first time. TcdA exhibited no glucosyltransferase-independent necrotic effect and was, thus, a good control to elucidate the underlying mechanism of the glucosyltransferase-independent effect of TcdB. We found RAS to be a central upstream regulator of the glucosyltransferase-independent effect of TcdB. The inhibition of RAS led to a 68% reduction in necrosis. Further analysis revealed apolipoprotein C-III (APOC3) as a possible crucial factor of CDI-induced inflammation in vivo.

Risk-aware temporal cascade reconstruction to detect asymptomatic cases.

This paper studies the problem of detecting asymptomatic cases in a temporal contact network in which multiple outbreaks have occurred. We show that the key to detecting asymptomatic cases well is taking into account both individual risk and the likelihood of disease-flow along edges. We consider both aspects by formulating the asymptomatic case detection problem as a directed prize-collecting Steiner tree (Directed PCST) problem. We present an approximation-preserving reduction from this problem to the directed Steiner tree problem and obtain scalable algorithms for the Directed PCST problem on instances with more than 1.5M edges obtained from both synthetic and fine-grained hospital data. On synthetic data, we demonstrate that our detection methods significantly outperform various baselines (with a gain of 3.6 × ). We apply our method to the infectious disease prediction task by using an additional feature set that captures exposure to detected asymptomatic cases and show that our method outperforms all baselines. We further use our method to detect infection sources ("patient zero") of outbreaks that outperform baselines. We also demonstrate that the solutions returned by our approach are clinically meaningful by presenting case studies.

Evaluation of Risk Factors for Clostridium difficile Infection Based on Immunochromatography Testing and Toxigenic Culture Assay.

In recent years, the diagnostic method of choice for Clostridium difficile infection (CDI) is a rapid enzyme immunoassay in which glutamate dehydrogenase (GDH) antigen and C. difficile toxin can be detected (C. diff Quik Chek Complete; Alere Inc.) (Quik Chek). However, the clinical significance remains unclear in cases that demonstrate a positive result for GDH antigen and are negative for toxin. In this study, we used the Quik Chek test kit on fecal samples, with an additional toxin detection step using a toxigenic culture assay for the aforementioned cases. CDI risk factors were assessed among the 3 groups divided by the Quik Chek test results. The study involved 1,565 fecal samples from patients suspected to have CDI who were hospitalized during the period of April 2012 to March 2014. The 3 groups were defined as follows: both GDH antigen positive and toxin positive (by Quik Chek test) (toxin-positive [TP] group, n = 109), both GDH antigen and toxin negative (toxin-negative [TN] group, n = 111), and positive only for GDH antigen but toxin positive with subsequent toxigenic culture (toxigenic culture [TC] group, n = 72). The gender, age, number of hospitalization days, white blood cell (WBC) counts, serum albumin levels, body mass index (BMI), fecal consistency, and use of antibacterials and proton pump inhibiters (PPIs) were analyzed. The positive rate for the fecal direct Quik Chek test was 7.0% (109/1,565 cases). However, toxigenic culture assays using the Quik Chek test for only the GDH-antigen-positive/toxin-negative samples were 35.3% positive (72/204 cases). As a result, the true positive rate for C. difficile toxin detection was estimated to be 11.6% (181/1,565 cases). Moreover, significant differences (P < 0.05) in the number of hospitalization days (>50 days), WBC counts (>10,000 WBCs/µl), and use of PPIs comparing the TN, TP, and TC groups, were observed. The odds ratios (ORs) for the development of CDI were 1.61 (95% confidence interval [CI], 0.94 to 2.74) and 2.98 (95% CI, 1.59 to 5.58) for numbers of hospitalization days, 2.16 (95% CI, 1.24 to 3.75) and 2.24 (95% CI, 1.21 to 4.14) for WBC counts, and 9.03 (95% CI, 4.9 to 16.6) and 9.15 (95% CI, 4.59 to 18.2) for use of PPIs in the TP and TC groups, respectively. These findings demonstrated that the use of PPIs was a significant risk factor for CDI development. Moreover, antibacterials such as carbapenems, cephalosporins, and fluoroquinolones were demonstrated to be risk factors. In conclusion, identification of the TC group of patients is thought to be important, as this study demonstrates that this group bears the same high risk of developing CDI as the TP group.

Insights From the 2016 Peer Kidney Care Initiative Report: Still a Ways to Go to Improve Care for Dialysis Patients.

Although outcomes improved during the past decade for patients receiving maintenance dialysis, gains were few in certain key areas, as highlighted in the 2016 Peer Kidney Care Initiative Report. Overall incidence rates of dialysis therapy initiation in adults remained relatively stable (∼42 per 100,000 US population, 2009-2013), but rates varied more than 2-fold, from 26 to 54, across US geographic regions. Hospitalization rates in incident patients decreased from 261 hospitalizations per 100 patient-years in 2003 to 207 in 2012, but observation stay rates increased from 40 to 67, attenuating the decline in hospitalizations by half. Decreases in prevalent patient hospitalizations for heart failure, from 15.6 per 100 patient-years in 2004 to 9.5 in 2013, were partially offset by increases in hospitalizations for volume overload, from 3.0 in 2004 to 6.1 in 2013. Prevalent patient rates of hospitalizations for arrhythmias (∼4.6 per 100 patient-years) did not improve during the past decade, whereas sudden cardiac death as a proportion of total cardiovascular deaths increased from 53% to 73%. Hospitalization rates for pneumonia/influenza, at about 8.3 per 100 patient-years in prevalent patients, did not decrease during this period, while hospitalization rates for bacteremia/sepsis increased from 8.6 to 12.0. If decreases in mortality rates are to be sustained, novel approaches to these challenges will be required.

Clostridium Difficile, Colitis, and Colonoscopy: Pediatric Perspective.

PURPOSE OF THE REVIEW: Review tests available for detection of Clostridium difficile (C. Diff) induced disease, including when such tests should be done in children and how they should be interpreted. RECENT FINDINGS: Multiple tests are available for detecting disease due to C. diff. These include colonoscopy and stool analysis. Colonoscopy with biopsy is the most sensitive test for detecting the presence of colitis. The toxins produced by the C. diff. (toxin A, toxin B, and binary toxin) are the agents that cause injury and disease. Only toxin producing C. diff. Strains will cause disease. Binary toxin by itself is not thought to produce disease. Binary toxin causes disease in humans when present with toxin A and B producing bacteria, and has been implicated with fulminant life threatening disease. Stool analyses vary in sensitivity and specificity depending on the assay used. The presence of toxin producing strains of C diff. in the stool does not equate with disease. The presence of a toxin-producing bacteria or toxins (A or B) only equates with disease if diarrhea or a diseased colon (toxic megacolon, ileus, and sepsis) is present. Nucleic acid amplification testing (NAAT), when used in the stool from patients with diarrhea, appears to be the most efficient study to detect the gene that encodes for toxin A and B and thus to diagnose C. diff.-induced disease. Infants have a high carriage rate of C. diff. and are believed not to develop disease from it or its toxins. Infants should not be tested for C. difficile. The NAAT is most specific when done on patients with diarrhea with liquid stools. Testing for C. difficile should only be done on patients with diarrhea. One can assume that a patient who has no diarrhea and is not ill does not have C. diff.-induced disease. Treatment should be limited to patients with diarrhea who test positive for C. diff. toxin (A or B) or toxin-producing bacteria. Direct testing for binary toxin is not commercially available. Binary toxin is only thought to cause disease in humans when C. diff. toxin (A and B)-producing bacteria are present.

The Risks of Incident and Recurrent Clostridium difficile-Associated Diarrhea in Chronic Kidney Disease and End-Stage Kidney Disease Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: The objective of this systematic review and meta-analysis was to assess the risks of incident and recurrent Clostridium difficile-associated diarrhea in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) requiring dialysis. METHODS: A literature search was performed from inception to February 2015. Studies that reported relative risks, odds ratios, or hazard ratios comparing the risks of C. difficile-associated diarrhea in patients with CKD or ESRD versus those without CKD or ESRD were included. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a random-effect, generic inverse variance method. RESULTS: Twenty studies (nine case-control, seven cohort, and four cross-sectional studies with 162,218,041 patients) were included in the meta-analysis. Pooled RRs of C. difficile-associated diarrhea in patients with CKD and ESRD were 1.95 (95% CI 1.81-2.10) and 2.63 (95% CI 2.04-3.38), respectively. When meta-analysis was limited only to cohort and case-control studies with confounder-adjusted analysis, the pooled RRs of C. difficile-associated diarrhea in patients with CKD and ESRD were 1.89 (95% CI 1.75-2.05) and 2.50 (95% CI 1.49-4.17), respectively. The pooled RR of recurrent C. difficile-associated diarrhea in patients with CKD was 2.61 (95% CI 1.53-4.44). Data on the risk of recurrent C. difficile-associated diarrhea were limited. CONCLUSION: This meta-analysis demonstrates significantly increased risks of incident and recurrent C. difficile-associated diarrhea in patients with CKD. Furthermore, the magnitude of increased risk of C. difficile-associated diarrhea in ESRD patients is even higher.

Management of Clostridioides difficile Infection: Diagnosis, Treatment, and Future Perspectives.

Clostridioides difficile infection is the most common healthcare-associated infection in the United States, with potential life-threatening complications and a significant impact on the costs of care. Antibiotic stewardship as well as discontinuation of chronic acid suppressive therapy are key for its prevention and treatment. Effective infection management requires appropriate interpretation of diagnostic tests, as well as the use of vancomycin and fidaxomicin as first-line treatment. Novel treatments such as Bezlotoxumab, fecal microbiota transplant, and live biotherapeutic products are proven effective in recurrent C. difficile infection and address dysbiosis.

Cytomegalovirus-Associated Colitis as a Cause of Lower Gastrointestinal Bleeding in Kidney Transplant Recipients: A Single-Centered Study.

Introduction Cytomegalovirus (CMV) is the most common viral pathogen affecting patients undergoing solid organ transplantation. It is often the most important infection for patients who have undergone kidney transplantation. Clinical presentations of cytomegalovirus infection range from asymptomatic infection to organ-specific involvement. This study aimed to determine the frequency of cytomegalovirus-associated colitis in kidney transplant recipients (KTRs) presenting with lower gastrointestinal bleeding. Methods After the approval of the ethical review committee of the Sindh Institute of Urology and Transplantation (ERC-SIUT), this cross-sectional study was conducted at the Department of Hepatogastroenterology at the Sindh Institute of Urology and Transplantation from January 2021 to December 2021. All the KTRs (six months after the transplantation) of either gender and aged between 18 and 65 years, presenting with lower gastrointestinal (GI) bleeding as per the operational definition, were enrolled in the study. Those patients who were either unfit for the endoscopy or refused to give consent were excluded from the study. Colonic biopsies were reviewed by a consultant histopathologist for the features of CMV infection. Results A total of 95 renal transplant recipients of either gender or age above 18 to 65 years with lower GI bleeding were included in the study. Among them, 84 (88.4%) were males, while 11 (11.6%) were females. The mean age of the patients included in the study was 37±11 years. The most common presenting complaint was fresh bleeding per rectum, which was observed in 73 (76.8%). The most common findings observed on colonoscopy in KTRs with bleeding per rectum were colonic ulcers and erosions noted in 41 (43.1%) and 36 (37.3%) patients, respectively. On histopathology, CMV colitis was noted in 21 (22.1%) patients. On comparison of different baseline variables, the presence of fresh bleeding per rectum and the presence of both ulcers and erosions on colonoscopy were the factors significantly associated with CMV colitis in KTRs. Conclusion CMV colitis is a prevalent condition in KTRs, presenting with lower GI bleeding. Despite the significant occurrence, the levels of CMV viremia were not associated with CMV colitis, suggesting that diagnosis should rely on histopathological confirmation. Prophylaxis during periods of high immunosuppression is crucial to reducing the incidence of CMV infections and improving both graft function and patient survival.

Preferences for a Clostridioides difficile vaccine among adults in the United States.

INTRODUCTION: Clostridioides difficile (C.diff) infection (CDI) causes significant morbidity and mortality among older adults. Vaccines to prevent CDI are in development; however, data on the target population's preferences are needed to inform vaccination recommendations in the United States (US). This study assessed US adults' willingness to receive a C.diff vaccine and examined how vaccine attributes influence their choices. METHODS: A cross-sectional online survey with a discrete choice experiment (DCE) was conducted among US adults aged ≥50 years. DCE attributes included effectiveness, duration of protection, reduction in symptom severity, out-of-pocket (OOP) costs, number of doses, and side effects. The DCE included 11 choice tasks, each with two hypothetical vaccine profiles and an opt-out (i.e., no vaccine). Attribute-level preference weights were estimated using hierarchical Bayesian modeling. Attribute relative importance (RI) was compared between select subgroups. RESULTS: Of 1216 adults in the analyses, 29.9% reported they knew either 'a little' (20.7%) or 'a lot' (9.2%) about C.diff before the study. A C.diff vaccine was chosen 58.0% of the time (vs. opt-out) across choice tasks. It was estimated that up to 75.0% would choose a vaccine when OOP was $0. Those who were immunocompromised/high-risk for CDI (vs. not) more frequently chose a C.diff vaccine. Decreases in OOP costs (RI = 56.1), improvements in vaccine effectiveness (RI = 17.7), and reduction in symptom severity (RI = 10.3) were most important to vaccine choice. The rank ordering of attributes by importance was consistent across subgroups. CONCLUSION: OOP cost, improvements in vaccine effectiveness, and reduction in CDI severity were highly influential to vaccine selection. Most adults aged ≥50 years were receptive to a C.diff vaccine, especially with little-to-no OOP cost, suggesting that mandating insurance coverage of vaccination with no copayment may increase uptake. The limited awareness about C.diff among adults presents an opportunity for healthcare providers to educate their patients about CDI prevention.

Long-term beneficial effect of faecal microbiota transplantation on colonisation of multidrug-resistant bacteria and resistome abundance in patients with recurrent Clostridioides difficile infection.

BACKGROUND: Multidrug-resistant (MDR) bacteria are a growing global threat, especially in healthcare facilities. Faecal microbiota transplantation (FMT) is an effective prevention strategy for recurrences of Clostridioides difficile infections and can also be useful for other microbiota-related diseases. METHODS: We study the effect of FMT in patients with multiple recurrent C. difficile infections on colonisation with MDR bacteria and antibiotic resistance genes (ARG) on the short (3 weeks) and long term (1-3 years), combining culture methods and faecal metagenomics. RESULTS: Based on MDR culture (n = 87 patients), we notice a decrease of 11.5% in the colonisation rate of MDR bacteria after FMT (20/87 before FMT = 23%, 10/87 3 weeks after FMT). Metagenomic sequencing of patient stool samples (n = 63) shows a reduction in relative abundances of ARGs in faeces, while the number of different resistance genes in patients remained higher compared to stools of their corresponding healthy donors (n = 11). Furthermore, plasmid predictions in metagenomic data indicate that patients harboured increased levels of resistance plasmids, which appear unaffected by FMT. In the long term (n = 22 patients), the recipients' resistomes are still donor-like, suggesting the effect of FMT may last for years. CONCLUSIONS: Taken together, we hypothesise that FMT restores the gut microbiota to a composition that is closer to the composition of healthy donors, and potential pathogens are either lost or decreased to very low abundances. This process, however, does not end in the days following FMT. It may take months for the gut microbiome to re-establish a balanced state. Even though a reservoir of resistance genes remains, a notable part of which on plasmids, FMT decreases the total load of resistance genes.

Atypical Clostridium difficile Infection in a Pregnant Patient: A Case Study on Non-Diarrheal Presentation and Syndrome of Inappropriate Antidiuretic Hormone (SIADH) Complication.

Clostridium difficile (C. difficile) is a Gram-positive, spore-producing bacterium that often leads to pseudomembranous colitis, typically manifesting as watery diarrhea. The risk factors for C. difficile infection (CDI) include exposure to broad-spectrum antibiotics, immunocompromised states, advanced age, usage of proton pump inhibitors (PPI), and comorbid conditions such as chronic kidney disease (CKD). This report details a case involving a 23-year-old pregnant woman who presented with symptoms of abdominal pain and constipation. She was diagnosed with a urinary tract infection (UTI) and treated with ceftriaxone. During her hospitalization, she was administered opioid pain relievers and underwent an intensive bowel regimen. Despite these measures, her constipation and abdominal discomfort persisted, and magnetic resonance imaging (MRI) of the abdomen revealed significant dilatation of the large bowel. The patient, discovered to have hyponatremia, underwent further evaluation. This revealed elevated urine osmolality and decreased blood plasma osmolality, indicative of a syndrome of inappropriate antidiuretic hormone secretion (SIADH). The patient received treatment with hypertonic saline. Later in her hospital stay, she tested positive for CDI through stool analysis and was treated with oral vancomycin. This case underscores the importance of considering CDI as a differential diagnosis in cases of ileus, abdominal pain, and constipation, especially in patients with notable risk factors for CDI. It highlights that the presence of diarrhea or watery bowel movements is not a necessary symptom for CDI testing.

A Review on Clostridioides Difficile Testing and How to Approach Patients With Multiple Negative Tests: A Case Report.

Clostridioides difficile (C. difficile) is an important nosocomial infection that is commonly associated with antibiotic use with pseudomembranous colitis being present in only 13% of cases. Disease severity ranges from asymptomatic carriers to severe complicated disease, based on clinical and laboratory findings. There is no single rapid FDA-approved test to diagnose C. difficile infections (CDI) and diagnosis usually requires a multi-step diagnostic approach. C. difficile testing usually begins with the C. difficile toxin and glutamate dehydrogenase antigen screen (GDH). If testing is negative for either, then nucleic acid amplification testing (NAAT) is done to confirm the diagnosis. Endoscopic evaluation may be required in rare instances when there is a high clinical suspicion of disease with negative testing. Here, we present an interesting case of a patient with multiple negative C. difficile toxin and GDH tests. Given the high index of clinical suspicion of CDI, the patient underwent a colonoscopy which revealed diffuse pseudomembranous colitis. The patient was then appropriately treated with oral vancomycin. We aim to shed light on the different testing modalities available to clinicians and the indications for doing a colonoscopy to delineate between false positive testing and active CDI.

A Unique Case of Pseudomonas aeruginosa-Associated Diarrhea in a Long-Term Hospitalized Adult Patient.

A 53-year-old Caucasian man with a history of alcohol use disorder, hypertension, and hypothyroidism presented with a myxedema coma requiring intubation. He had a complicated hospital course with ventilator-associated pneumonia with MRSA, sepsis with candida, and abdominal compartment syndrome requiring decompressive laparotomy. The patient slowly recovered during 43 days of hospitalization. During the intensive care unit (ICU) stay, a flexi-seal rectal tube was placed due to fecal incontinence. After being moved to a regular medicine unit, he started having loose watery stools with leukocytosis and neutrophilia. Clostridium difficile (C. diff.) colitis was suspected, and he was placed on oral vancomycin empirically. His stool test for C. diff. came back negative, and his rectal tube was subsequently removed. Imaging did not show any abscess, perforated viscus, or fistula formations. His stool culture grew a heavy colony of Pseudomonas aeruginosa (P. aeruginosa). Vancomycin was stopped, and he was started on oral ciprofloxacin 750 mg twice a day with complete resolution of his diarrhea and leukocytosis.

Fecal Microbiota Transplantation for Fulminant Clostridioides Difficile Infection: A Combined Medical and Surgical Case Series.

INTRODUCTION: Urgent abdominal colectomy is indicated for patients with fulminant Clostridioides difficile infection (CDI) when other medical therapies fail, yet mortality remains high. Fecal microbiota transplant is a less invasive alternative approach for patients with fulminant CDI. We report the 30-day complications of patients with fulminant CDI who underwent either abdominal colectomy, fecal microbiota transplantation (FMT), or FMT followed by abdominal colectomy (FMT-CO). Methods: We performed a single-center, retrospective case review of combined medical and surgical patients with CDI at a large academic medical center between 2008 and 2016. Cohorts were identified as patients with fulminant CDI who underwent total abdominal colectomy alone (CO), FMT alone (FMT), or FMT-CO. We analyzed patient demographics, history, comorbidities, clinical and laboratory variables, CDI severity scores, and mortality outcomes at 30 days. Results: We identified 5,150 patients with CDI at our center during the review period; 16 patients met the criteria for fulminant CDI and were included in this study, with four patients in the CO cohort, eight patients in the FMT cohort, and four patients in the FMT-CO cohort. Demographics and CDI severity scores were similar for all three groups, although the selected comorbidity profiles differed significantly among the three cohorts. The 30-day mortality rates for patients in the CO, FMT, and FMT-CO groups were 25%, 12.5%, and 25%, respectively. Conclusions: FMT is an alternative or adjunctive therapy to colectomy for patients with fulminant CDI that is not associated with increased mortality. Implementation of FMT protocols in clinical practice would be dependent on the availability of qualified transplant material and successful early identification of patients likely to benefit from FMT.

Clostridium difficile Infection Rates During the Pandemic in New York Capital Area: A Single-Center Study.

Introduction Clostridioides difficile (C. difficile) colonizes the large intestine, rendering healthy individuals asymptomatic carriers of the disease. In certain instances, C. difficile infection (CDI) occurs. Antibiotic use remains the leading risk factor for CDI. During the coronavirus disease 2019 (COVID-19) pandemic, multiple risk and protective factors for and against CDI were identified, and as such multiple studies tried to analyze the pandemic's overall effect on CDI incidence rates, with contradictory results. Our study's aim is to further characterize the CDI incidence rates trends, but for a longer period of 22 months in the pandemic. Methods We included only adult (>18 years) patients, diagnosed with CDI during their hospitalization for the following period: January 1, 2018, to December 31, 2021. Incidence was calculated as cases per 10,000 patient days. The period identified as the COVID-19 pandemic period was the following: March 1, 2020, to December 31, 2021. All analyses were performed by an expert statistician using Minitab software (Minitab Inc., State College, Pennsylvania, United States). Results The mean CDI incidence rate per 10,000 patient-days was 6.86 +/-2.1. The 95% confidence interval for the CDI incidence rate prior to the pandemic was found at 5.67 +/-0.35 while the interval during the pandemic was calculated at 8.06 +/- 0.41 per 10,000 patient days. Those results reveal a statistically significant increase in CDI incidence rates during the COVID-19 era. Conclusion Multiple risk and protective factors for and against hospital-acquired infections (including CDI) have been identified during the unprecedented COVID-19 healthcare crisis. In the literature, there is high controversy regarding the trends of CDI incidence during the pandemic. The current study analyzed an almost two-year period into the pandemic, identifying an increase in CDI rates when compared to the pre-pandemic era.

A Rare Case of Polymerase Chain Reaction-Negative Severe Clostridioides difficile Infection.

Accurately diagnosing Clostridioides difficile infection (CDI) is crucial for effective patient management. A misdiagnosis poses risks to patients, leads to treatment delays, and contributes to infection transmission in healthcare settings. While using polymerase chain reaction (PCR) to amplify the toxin B gene is a sensitive method for detecting toxigenic C. difficile, there is still a risk of false-negative results. These inaccuracies could have significant consequences for diagnosing and treating CDI, emphasizing the need for careful consideration and other diagnostic approaches. This case report highlights a patient with severe CDI who had negative PCR and toxin and a biopsy showing pseudomembranous colitis on further testing due to persistence and worsening of symptoms. In the diagnosis of C. difficile infection, healthcare providers should consider clinical symptoms, although diarrhea, which is a major sign of CDI, can be due to other causes. Even in the presence of negative PCR results, if a patient displays symptoms consistent with C. difficile-associated disease, healthcare providers may still contemplate treatment.