Common Cause Of Hospital-acquired Diarrhea Research Articles

Dual RNA-seq identifies genes and pathways modulated during Clostridioides difficile colonization.

The gastrointestinal pathogen Clostridioides difficile is the most common cause of hospital-acquired diarrhea. Bacterial interactions with the gut mucosa are crucial for the establishment of C. difficile infection; however, key infection events like bacterial attachment and gut penetration are still poorly defined. To better understand the initial events that occur when this anaerobe interacts with the human gut epithelium, we employed a dual RNA-sequencing approach to study the bacterial and host transcriptomic profiles during C. difficile infection in a dual environment in vitro human gut model. Temporal changes in gene expression during infection were studied in bacterial and epithelial cells over 3-24 hours. While there were several common differentially expressed bacterial genes across different timepoints after infection, mammalian transcriptional profiles were quite distinct, with little overlap. Interestingly, an induction of colonic receptors for C. difficile toxins was observed, along with the downregulation of genes encoding immune response markers. Several cell wall-associated proteins were downregulated in C. difficile when associated with host cells, including slpA, which encodes the main S-layer protein. Gene function and pathway enrichment analyses revealed a potential modulation of the purine/pyrimidine synthesis pathways both in the mammalian and bacterial cells. We observed that proline-proline endopeptidase, a secreted metalloprotease responsible for cell surface protein cleavage, is downregulated during infection, and a mutant lacking this enzyme demonstrated enhanced adhesion to epithelial cells during infection. This study provides new insight into the host and bacterial pathways based on gene expression modulation during the initial contact of C. difficile with gut cells. IMPORTANCE The initial interactions between the colonic epithelium and the bacterium are likely critical in the establishment of Clostridioides difficile infection, one of the major causes of hospital-acquired diarrhea worldwide. Molecular interactions between C. difficile and human gut cells have not been well defined mainly due to the technical challenges of studying cellular host-pathogen interactions with this anaerobe. Here we have examined transcriptional changes occurring in the pathogen and host cells during the initial 24 hours of infection. Our data indicate several changes in metabolic pathways and virulence-associated factors during the initial bacterium-host cell contact and early stages of infection. We describe canonical pathways enriched based on the expression profiles of a dual RNA sequencing in the host and bacterium, and functions of bacterial factors that are modulated during infection. This study thus provides fresh insight into the early C. difficile infection process.

Clostridium difficile Infection: Risk and Poor Prognostic Factors at a Tertiary Hospital in the Eastern Region of Saudi Arabia.

Clostridium difficile (C. difficile) is a common cause of hospital-acquired diarrhea. It is associated with significantly higher mortality and morbidity in addition to the cost-effectiveness burden on the healthcare system. The primary risk factors for C. difficile infection (CDI) are past C. difficile exposure, proton pump inhibitors, and antibiotic usage. These risk factors are also associated with poor prognosis. This study was performed in Dr. Sulaiman Al Habib Tertiary Hospital in the Eastern Region of Saudi Arabia. The aim was to evaluate the risk and prognostic factors of CDI and their association with the outcomes of hospital stay, such as complications, length of stay (LOS), and treatment duration. This is a retrospective cohort study for all patients who tested for C. difficile in the medical department. The target population was all adult patients ≥16 years with positive stool toxins for C. difficile between April 2019 and July 2022. The main outcome measures are risk and poor prognostic factors for CDI. C. difficle infection patients were included in the study; 12 (52.2%) were female, and 11 (47.8%) were male. The mean age of the patients was 58.3 (SD: 21.5) years; 13 (56.5%) patients were below 65 years, and 10 were above 65 years. Only four patients were without comorbidities, and 19 (82.6%) patients had various comorbidities. Importantly, hypertension was the most common comorbidity in 47.8% of the patients. Furthermore, advanced age significantly impacted the hospital LOS as the mean age among patients who stayed at the hospital less than four days and those who stayed ≥4 days was 49.08 (19.7) and 68.36 (19.5), respectively (P = .028). Advanced age was the most frequent poor prognostic factor among our inpatient participants with positive CDI. It was significantly associated with longer hospital LOS, more complications, and longer treatment duration.

Clostridioides difficile infection after cardiac surgery: Assessment of prevalence, risk factors and clinical outcomes-retrospective study.

BackgroundClostridioides difficile infection (CDI) is the most common cause of hospital-acquired diarrhea. There is little available data regarding risk factors of CDI for patients who undergo cardiac surgery. The study evaluated the course of CDI in patients after cardiac surgery.MethodsOf 6,198 patients studied, 70 (1.1%) developed CDI. The control group consisted of 73 patients in whom CDI was excluded. Perioperative data and clinical outcomes were analyzed.ResultsPatients with CDI were significantly older in comparison to the control group (median age 73.0 vs 67.0, P = 0.005) and more frequently received proton pump inhibitors, statins, β-blockers and acetylsalicylic acid before surgery (P = 0.008, P = 0.012, P = 0.004, and P = 0.001, respectively). In addition, the presence of atherosclerosis, coronary disease and history of malignant neoplasms correlated positively with the development of CDI (P = 0.012, P = 0.036 and P = 0.05, respectively). There were no differences in the type or timing of surgery, aortic cross-clamp and cardiopulmonary bypass time, volume of postoperative drainage and administration of blood products between the studied groups. Relapse was more common among overweight patients with high postoperative plasma glucose or patients with higher C-reactive protein during the first episode of CDI, as well as those with a history of coronary disease or diabetes mellitus (P = 0.005, P = 0.030, P = 0.009, P = 0.049, and P = 0.025, respectively). Fifteen patients died (21.4%) from the CDI group and 7 (9.6%) from the control group (P = 0.050). Emergent procedures, prolonged stay in the intensive care unit, longer mechanical ventilation and high white blood cell count during the diarrhea were associated with higher mortality among patients with CDI (P = 0.05, P = 0.041, P = 0.004 and P = 0.007, respectively).ConclusionsThe study did not reveal any specific cardiac surgery-related risk factors for development of CDI.

Clostridium difficile fecal toxin level is associated with disease severity and prognosis

Antibiotic-associated colitis caused by Clostridium difficile (C. difficile) is the most common cause of hospital-acquired diarrhea. The pathogenesis of C. difficile colitis is mediated by bacterial toxins. C. difficile infection (CDI) severity may be determined by the fecal level of these toxins. The objective of this article is to determine whether fecal C. difficile toxin (CDT) levels are associated with disease severity and prognosis. A cross-sectional study of patients admitted with CDI in a tertiary center between 2011 and 2015 was conducted. Fecal CDT levels were determined by quantitative ELISA. Severe CDI was defined as a leukocyte count of > 15 × 103 cells/μl, creatinine levels that deteriorated by > 1.5 times the baseline level, or albumin levels < 3 g/dl. Seventy-three patients were recruited for this study. Patients with severe CDI (n = 47) had significantly higher toxin levels compared to patients with mild to moderate CDI (n = 26) (651 ng/ml (IQR 138-3200) versus 164 ng/ml (IQR 55.2-400.1), respectively; p = 0.001). A high toxin level (>2500 ng/ml) was associated with an increased mortality rate (odds ratio 11.8; 95% confidence interval 2.5-56). The fecal CDT level is associated with disease severity and mortality rate. Measuring CDT levels may be an objective and accurate way to define the severity of CDI.

Sa1763 - Clostridium Difficile Fecal Toxin Level is Associated with Disease Severity and Prognosis

BackgroundAntibiotic-associated colitis caused by Clostridium difficile (C. difficile) is the most common cause of hospital-acquired diarrhea. The pathogenesis of C. difficile colitis is mediated b...

A Diagnostic Algorithm for the Detection of Clostridium difficile-Associated Diarrhea.

Clostridium difficile is a common cause of hospital-acquired diarrhea, which is usually associated with previous antibiotic use. The clinical manifestations of C. difficile infection (CDI) may range from mild diarrhea to fulminant colitis. Clostridium difficile should be considered in diarrhea cases with a history of antibiotic use within the last 8 weeks (community-associated CDI) or with a hospital stay of at least 3 days, regardless of the duration of antibiotic use (hospital-acquired CDI). This study investigated the frequency of CDI in diarrheic patients and evaluated the efficacy of the triple diagnostic algorithm that is proposed here for C. difficile detection. Cross-sectional study. In this study, we compared three methods currently employed for C. difficile detection using 95 patient stool samples: an enzyme immunoassay (EIA) for toxin A/B (C. diff Toxin A+B; Diagnostic Automation Inc.; Calabasas, CA, USA), an EIA for glutamate dehydrogenase (GDH) (C. DIFF CHEK-60TM, TechLab Inc.; Blacksburg, VA, USA), and a polymerase chain reaction (PCR)-based assay (GeneXpert(®) C. difficile; Cepheid, Sunnyvale, CA, USA) that detects C. difficile toxin genes and conventional methods as well. In this study, 50.5% of the patients were male, 50 patients were outpatients, 32 were from inpatient clinics and 13 patients were from the intensive care unit. Of the 95 stool samples tested for GDH, 28 were positive. Six samples were positive by PCR, while nine samples were positive for toxin A/B. The hypervirulent strain NAP-1 and binary toxin was not detected. The rate of occurrence of toxigenic C. difficile was 5.1% in the samples. Cefaclor, ampicillin-sulbactam, ertapenem, and piperacillin-tazobactam were the most commonly used antibiotics by patients preceding the onset of diarrhea. Among the patients who were hospitalized in an intensive care unit for more than 7 days, 83.3% were positive for CDI by PCR screening. If the PCR test is accepted as the reference: C. difficile Toxin A/B ELISA sensitivity and specificity were 67% and 94%, respectively, and GDH sensitivity and specificity were 100% and 75%, respectively. Tests targeting C. difficile toxins are frequently applied for the purpose of diagnosing CDI in a clinical setting. However, changes in the temperature and reductant composition of the feces may affect toxin stability, potentially yielding false-negative test results. Therefore, employment of a GDH EIA, which has high sensitivity, as a screening test for the detection of toxigenic strains, may prevent false-negative results, and its adoption as part of a multistep diagnostic algorithm may increase accuracy in the diagnosis of CDIs.

Clostridium difficile infection in adult patients with acute myeloid leukemia: Incidence, recurrence, and outcomes.

e18020 Background: Clostridium difficile infection (CDI) is the most common cause of hospital-acquired diarrhea. Acute Myeloid Leukemia (AML) patients may have increased predisposition to CDI as we...

Clostridium difficile infection: a Serbian single-center experience.

Clostridium difficile infection (CDI) is the most common cause of hospital-acquired diarrhea. Severity of CDI is associated with advanced age and co-morbidities. The clinical spectrum varies from mild watery diarrhea to severe fulminant pseudomembranous colitis with complications. This study conducted over a six-year period (2008 to 2013) included 510 patients treated at the University Hospital for Infectious and Tropical Diseases in Belgrade, Serbia. In patients with a history of previous hospitalization and/or treatment with antimicrobial agents who developed diarrhea, the diagnosis was established with rapid tests for C. difficile toxin A and B and by stool culture for C. difficile (454 patients) or by endoscopic examination and histological analyses of the biopsy samples taken from the colonic mucosa (56 patients). The mean age of patients was 67.71±13.34 years. A total of 67.8% patients were older than 65 years. Over half (58.7%) of the patients were female. 93% had been previously hospitalized and/or had surgical interventions, during which they had been treated with antibiotics. In the clinical presentation spectrum, pseudomembranous colitis occurred in 51.0%. The mean duration of illness after the introduction of specific antibiotic therapy was 7.10 ± 4.88 days. Complications developed in 14 patients. The disease relapsed in 43 (8.4%). Thirty-two (6.3%) patients died, mostly due to co-morbidities. CDI is the most important cause of hospital-acquired diarrhea in Serbia. The disease mainly affects elderly patients with co-morbidities. The incidence of complications is low and prognosis is age dependent and related to pre-existing diseases.

Factors associated with Clostridium difficile diarrhea in a hospital in Beijing, China

Clostridium difficile is the most common cause of hospital-acquired diarrhea in patients treated with antibiotics, chemotherapeutic agents, and other drugs that alter the normal equilibrium of the intestinal flora. A better understanding of the risk factors for C. difficile-associated disease (CDAD) could be used to reduce the incidence of CDAD and the costs associated with its treatment. The aim of this study was to identify the risk factors for CDAD in a cohort of Chinese patients in a Beijing hospital. Medical charts of a total of 130 inpatients (62 males and 68 females) with hospital-acquired diarrhea (45 with CDAD; 85 without CDAD) were retrospectively reviewed. C. difficile toxins A and B were detected in fecal samples using enzyme-linked fluorescence assays. The drugs used by patients with and without CDAD before the onset of diarrhea were compared. Factors that differed significantly between the two groups by univariate analysis were analyzed by multivariate analysis using a logistic regression model. Multivariate analysis showed that cephalosporin treatment was associated with a significantly higher risk of CDAD in hospitalized patients, while treatment with glycopeptides was significantly associated with a reduction in CDAD (P<0.001 for cephalosporin; P=0.013 for glycopeptides). Our data confirmed previous findings that empirical treatment with cephalosporins is positively associated with CDAD compared to individuals using other CDAD-related drugs. Additionally, we showed that treatment with glycopeptides was negatively associated with CDAD, compared to individuals using other CDAD-related drugs.

Clostridium difficile: Deleterious Impact on Hematopoietic Stem Cell Transplantation

C. difficile infection (CDI), the most common cause of hospital-acquired diarrhea, is very frequent after hematopoietic stem cell transplantation (HSCT). Recent publications suggest it affects between 6% and 20% of HSCT recipients during the first year and is more common following allogeneic transplant (allo-HSCT). The best diagnostic strategy remains to be defined, but molecular testing for the toxin genes by polymerase chain reaction (PCR) seems to be replacing the traditional enzyme immunoassays (EIA). The higher sensitivity of the PCR may result in increased measured incidence of disease. C. difficile infection typically occurs during the first month after HSCT. Although the course of CDI after HSCT does not seem to be different than in other hospitalized patients, it may result in worsening of bowel graft versus host disease (GVHD) after allo-HSCT. Current evidence suggests a reciprocal effect by which GVHD may increase the risk of CDI and C. difficile disease may increase the risk of GVHD. Metronidazole was the treatment most commonly used in all recent series, followed by the combination metronidazole and oral vancomycin. There is minimal information on the use of fidaxomicin in HSCT recipients. Regarding stool transplant, there is one case report of successful use of this modality in an HSCT recipient. These two newer approaches will certainly be investigated in the future.

Does Gastrointestinal Dysmotility Predispose to Recurrent or Severe Forms of Clostridium difficile Infections?

Clostridium difficile infection (CDI) is the most common cause of hospital-acquired diarrhea. A limited number of studies have looked at the risk factors for recurrent CDI. Mitochondrial NeuroGastroIntestinal Encephalopathy (MNGIE) is a rare multisystemic disorder that causes gastrointestinal dysmotility. Herein we present a patient with MNGIE who suffered recurrent and severe C. difficile infection despite appropriate treatment. We aim to bring the gastroenterologist's attention to gastrointestinal dysmotility as a possible risk factor for the development of recurrent or severe forms of C. difficile infections.

Evaluation of a ChromIDC. difficileAgar for the Isolation ofClostridium difficile

Background: Clostridium difficile is the main etiologic agent of antibiotic-associated diarrhea and the most common cause of hospital-acquired diarrhea. Recently, the incidence of C. difficile infections (CDI) has increased and new highly virulent C. difficile strains have emerged. Therefore, accurate and rapid diagnosis is needed. We compared the results of using chromID C. difficile (chromID CD, bioMerieux, France) with the conventional C. difficile Selective Agar (CDSA; BD, USA) for the isolation of C. difficile. Methods: A total of 738 stool specimens of suspected CDI patients at the Severance Hospital from July to August 2011 were inoculated onto CDSA. Among them, 104 stool specimens revealed colonies on CDSA that were then re-inoculated onto chromID CD. The stool samples were stored at −20 o C until the time of the re-inoculation. Cultured agars were interpreted after 24 hrs and 48 hrs, respectively. Species identification was performed on the basis of colony characteristics on agar plates as well as the ATB 32A system (API System SA, France). Results: The recovery rates of CDSA and chromID CD were 30.1% and 77.5% after 24 hrs, and 77.5% and 98.6% after 48 hrs, respectively. All of the C. difficile isolates were recovered as typical gray/black colonies on chromID CD. Conclusion: The performance of chromID CD for the isolation of C. difficile was better than that of conventional CDSA. The chromID CD could provide easy and sensitive detection of C. difficile even after 24hrs of incubation. (Korean J Clin Microbiol 2012; 15:88-91)

Fulminant Clostridium Difficile Colitis After Surgical Treatment of Cervical Destructive Spondyloarthropathy: A Case Report.

The number of spinal surgical procedures in hemodialysis patients has increased with advances in medical management, but these procedures remain a challenge due to the high morbidity and mortality rate in this patient population. To our knowledge, destructive spondyloarthropathy in the cervical spine was first reported as a serious complication of hemodialysis by Kuntz et al.1 in 1984. Once present, destructive spondyloarthropathy can progress rapidly, resulting in severe spinal instability and consequently neurological compromise. Destructive spondyloarthropathy in the cervical spine requires an aggressive approach with surgical decompression and stabilization, but it carries a high risk of complications due to the underlying comorbidities. In eleven publications, there have been eighteen deaths reported in ninety-nine surgical cases of cervical spondyloarthropathy in hemodialysis patients2-12. Clostridium difficile infection (CDI) is a common cause of hospital-acquired diarrhea. The clinical presentation of CDI varies, ranging from an asymptomatic carrier state to a severe form of colitis, commonly known as fulminant C. difficile colitis (FCDC), which can lead to multiple organ failure. It is estimated that up to 3% of patients with CDI progress to FCDC13,14. Although progression to FCDC is uncommon, it is associated with a high mortality rate of 53% to 80%15,16. We present the case of a hemodialysis patient with cervical myelopathy due to destructive spondyloarthropathy who developed FCDC after surgical treatment of the cervical spine. We explained to the patient’s family that data concerning the case would be submitted for publication, and they gave their consent. A fifty-six-year-old woman with end-stage renal disease, secondary to kidney cysts, had been treated with maintenance hemodialysis for two years prior to presentation to us. She had developed neck pain, radiating into the right arm, which slowly worsened over a period of six months. …

Intravenous immunoglobulin for the treatment of severe Clostridium difficile colitis: An observational study and review of the literature

Clostridium difficile colitis (CDC) is the most common cause of hospital-acquired diarrhea. The increase in the incidence and fatality rate of CDC over the past decade has stimulated a search for new therapies, including intravenous immunoglobulin (IVIG). We report our experience with IVIG for the treatment of 21 patients with severe CDC. Retrospective review of patients with severe CDC who received IVIG between July 2002 and April 2006 at a teaching hospital. The existing literature on IVIG infusion for severe CDC was also reviewed. Twenty-one of 1230 patients with CDC were treated with IVIG. The mean age was 68 (range, 35-98) years, with mean hospital stay of 23 (range, 9-64) days. Conventional treatment was used for an average of 8 (range, 1-25) days before IVIG infusion. All patients had evidence of pancolitis (radiologically) or ileus (clinically). The mean Acute Physiological Assessment and Chronic Health Evaluation (APACHE II) score was 25 (range, 6-39) at day 1 of IVIG infusion. Nine patients (43%) survived their hospitalization with colitis resolution while 12 (57%) died. One patient developed pulmonary edema after IVIG infusion. Symptoms resolved after an average of 10 (range, 2-20) days for survivors. Two patients underwent urgent colectomy. This is the largest case series describing IVIG use for patients with severe CDC and the one with the highest mortality rate to date. The use of IVIG in this setting does not seem to benefit all patients. Benefit appears to depend on the extent of systemic involvement. Further studies are needed before adopting IVIG as routine treatment for severe CDC.

Clostridium difficile Infections — and Fluoroquinolones

Clostridium difficile is a common cause of hospital-acquired diarrhea; in the past, outbreaks have been associated with use of antibiotics, particularly cephalosporins, clindamycin, or ampicillin-amoxicillin. After the incidence of nosocomial C. difficile disease at a large Pittsburgh hospital increased from 2.7 cases per 1000 discharges in 1999 to 6.8 cases …

Polymerase chain reaction for identification and typing of Clostridium difficile isolated from Chinese patients

Objective: Toxigenic Clostridium difficile, the etiologic agent of C. difficile-associated diarrhea (CDAD), is the most common cause of hospital-acquired diarrhea in many developed countries. In spite of the endemic nature of diarrhea in China, few reports of C. difficile infection in this country have been documented in the literature. Methods: In this study, a polymerase chain reaction (PCR) assay was used to determine the presence of toxigenic C. difficile in the stools of 19 patients who developed diarrhea after antibiotic use in a hospital in China. Clostridium difficile was also cultured from the stool of these patients. After DNA extraction, PCR was performed with primers targeting C. difficile toxin A and toxin B gene sequences. Results: Toxin sequences were detected in 5 of 19 (26%) specimens analyzed. To determine strain identity, these isolates were genotyped using arbitrarily primed PCR (AP-PCR). Three APPCR profiles were identified among these isolates. Three of these isolates had the same DNA banding pattern, and they were isolated from patients who were at the same institution. Conclusions: These preliminary results indicate that C. difficile may be involved in some diarrhea cases in China. This study may aid in the understanding of the nature of endemic diarrhea in this country.