Clostridium Difficile Enteritis Research Articles

Stress Ulcer Prophylaxis in Cardiac Surgery: A Retrospective Cohort Study to Analyze the Effects of SUP Cessation.

Upper gastrointestinal bleeding (UGIB) is an important complication among critically ill adults, especially those having cardiac surgery as management is complicated by the requirement for antiplatelet/anticoagulant therapy. As a result, stress ulcer prophylaxis (SUP) has become routine practice in many centers, utilizing either proton pump inhibitors (PPIs) or histamine-2 receptor blockers (H2RBs). Recent evidence from the PEPTIC trial indicated an increase in mortality risk among cardiac surgery patients receiving PPIs compared to H2RBs. Considering these findings, alongside practical difficulties surrounding the transition to H2RBs as a prophylactic agent in New Zealand, Wellington Hospital intensive care unit elected to discontinue routine PPI use for SUP in cardiac surgery patients. A retrospective study was conducted to assess patient outcomes following the discontinuation of routine SUP. A retrospective cohort study was conducted of all adult patients who underwent cardiac surgery at Wellington Hospital between February/2018 and January/2022, and divided patients into cohorts before and after the discontinuation of routine use of SUP on the 31st of January 2020. The primary outcomes were the rate of UGIB, oesophagogastroduodenoscopy (OGD) and 180-day postoperative mortality. Secondary outcomes included rates of postoperative Clostridium difficile enteritis, pneumonia, deep sternal wound infection, and length of stay of the index admission. The rate of UGIB statistically significantly increased since the cessation of routine SUP in January 2020 (2.4% vs 5.4%, P-value = .004). This finding was mirrored with the increased rates of OGD (1.9% vs 4.0%, P-value = .005). There were no significant changes in 180-day mortality, hospital length of stay, or any of the postoperative infective complications analyzed, pneumonia, deep sternal wound infection, or C difficile enteritis. This study suggests an association between routine use of SUP and reduced rates of clinically significant UGIB and OGD requirements in cardiac surgery patients without increasing risk of infective complications or postoperative mortality.

S3522 A Rare Case of Clostridium difficile Enteritis in a Patient With Ileorectal Anastomosis and Loop Ileostomy

S3522 A Rare Case of Clostridium difficile Enteritis in a Patient With Ileorectal Anastomosis and Loop Ileostomy

Prophylactic acid suppressants in children in the intensive care unit: a systematic review with meta-analysis and trial sequential analysis.

Critically ill children are at risk of stress-induced gastrointestinal ulceration. Acid suppressants are frequently used in intensive care units even though there is uncertainty about the benefits and harms. With this systematic review, we aimed to assess patient-important benefits and harms of stress ulcer prophylaxis (SUP) in children in intensive care. We conducted the review according to the PRISMA statement, the Cochrane Handbook, and GRADE, using conventional meta-analysis and trial sequential analysis (TSA). We included randomised clinical trials comparing SUP with histamine-2-receptor antagonists or proton pump inhibitors vs placebo/no prophylaxis in children admitted for intensive care. Primary outcomes were all-cause mortality and overt gastrointestinal bleeding. Secondary outcomes were serious adverse events, hospital-acquired pneumonia, Clostridium difficile enteritis, myocardial ischemia, acute kidney injury and quality of life. We included a total of seven trials (n=504) with eight trial comparisons. We found no statistically significant difference in all-cause mortality (relative risk (RR) 1.43, 95% confidence interval (CI) 0.86-2.37), overt gastrointestinal bleeding (RR 0.75, 95% CI 0.42-1.35) or hospital-acquired pneumonia (RR 1.18, 95% CI 0.77-1.82) between SUP vs placebo/no prophylaxis. No trials reported on remaining secondary outcomes. TSA was unable to draw firm conclusions for all outcomes and certainty of evidence for all outcomes was "very low." We found no difference in all-cause mortality, overt gastrointestinal bleeding or hospital-acquired pneumonia in children in intensive care receiving acid suppressants compared with placebo/no prophylaxis. However, the quantity and quality of evidence was very low with no firm evidence for benefit or harm.

Prophylactic use of acid suppressants in adult acutely ill hospitalised patients: A systematic review with meta-analysis and trial sequential analysis.

Acutely ill patients are at risk of stress-related gastrointestinal (GI) bleeding and prophylactic acid suppressants are frequently used. In this systematic review, we assessed the effects of stress ulcer prophylaxis (SUP) with proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) versus placebo or no prophylaxis in acutely ill hospitalised patients. We conducted the review according to the PRISMA statement, the Cochrane Handbook and GRADE, using conventional meta-analysis and trial sequential analysis (TSA). The primary outcomes were all-cause mortality, clinically important GI bleeding and serious adverse events (SAEs). The primary analyses included overall low risk of bias trials. We included 65 comparisons from 62 trials (n=9713); 43 comparisons were from intensive care units. Only three trials (n=3596) had overall low risk of bias. We did not find an effect on all-cause mortality (RR 1.03, 95% CI 0.94 to 1.14; TSA-adjusted CI 0.90 to 1.18; high certainty). The rate of clinically important GI bleeding was lower with SUP (RR 0.62, 95% CI 0.43 to 0.89; TSA-adjusted CI 0.14 to 2.81; moderate certainty). We did not find a difference in pneumonia rates (moderate certainty). Effects on SAEs, Clostridium difficile enteritis, myocardial ischaemia and health-related quality of life (HRQoL) were inconclusive due to sparse data. Analyses of all trials regardless of risk of bias were consistent with the primary analyses. We did not observe a difference in all-cause mortality or pneumonia with SUP. The incidence of clinically important GI bleeding was reduced with SUP, whereas any effects on SAEs, myocardial ischaemia, Clostridium difficile enteritis and HRQoL were inconclusive. PROSPERO registration number CRD42017055676; published study protocol: Marker, et al 2017 in Systematic Reviews.

Inpatients With 'Unexplained' Leukocytosis

BackgroundUnexplained or persistent leukocytosis is an increasing common cause of consultation to infectious disease physicians. Patients appear to be in a state of continued inflammation recently described as the persistent inflammation-immunosuppression and catabolism syndrome (PICS). Hospital course of such patients is frequently prolonged and associated with extensive use of empiric broad-spectrum antibiotics. We wished to determine the associated clinical features and outcome of such patients in anticipation of future specific diagnostic and therapeutic approaches to this syndrome. MethodsWe reviewed all infectious disease consultations from July 1, 2017, to March 31, 2018, for reason for consultation. Of those whose primary reason was “leukocytosis” or “bandemia,” each chart was assessed for demographics, reason for admission, hospital day of consultation, peak white blood cell count, infections and possible microbiological colonization, antibiotic use, and outcome. ResultsA total of 29 patients were identified, constituting 4.5% of consults during the study period. Cause of admission was sepsis in 7, major trauma 6, cerebrovascular accident 5, major elective surgery 4, ischemic leg 3, and 1 each lung mass, acute myocardial infarction, interstitial lung disease, and angioblastic lymphoma. Peak total leukocyte count (WBC) was 26.4K ± 8.8 on mean day 9.6 ± 5.5 days of hospitalization. Mean duration of leukocytosis greater than 11K was 14.5 ± 10.6 days. Peak percentage early myelocytic (“band”) leukocytes was 18.4 ± 13.8 and was of higher than 5% for a duration of 4.5 ± 5.6 days. Total eosinophilia count >500 was observed in 15 patients (range 500-2800) median hospital day 12. All patients received multiple and prolonged courses of broad-spectrum combination empiric antibiotics without apparent benefit either in terms of leukocytosis, signs of sepsis if present, or change in cultures, although those 7 with confirmed sepsis at admission tended to have shorter duration of leukocytosis and hospital course, whereas patients with trauma manifested greatest “bandemia.” Most patients became colonized with resistant opportunistic organisms, the most significant being Clostridium difficile enteritis in 6 patients. Hospitalization was prolonged, and most common disposition was to nursing home or rehabilitation (11 patients, mean day of discharge 21.6 ± 16.8) and home (8 patients, day 16.0 ± 9.3). Three patients died at mean hospital day 35.7 ± 29.7. ConclusionsExcept for 1 person with pelvic abscess post-cystectomy, patients appeared to have extensive tissue damage rather than active infection driving the leukocytosis. Patients appeared to meet clinical criteria for PICS that was substantiated by development of eosinophilia. Future studies should include direct measurements of the CD33CD11b+ myeloid suppressor cells, and the relative contribution of damage-associated molecular patterns (DAMPS) compared with pathogen-associated molecular patterns (PAMPS) such as endotoxin and other microbial products. More prudent and effective use of antibiotics could be possible.

2600 A Typical Presentation of a Rare Disease: Clostridium difficile Enteritis After Total Abdominal Colectomy

INTRODUCTION: Clostridium difficile enteritis (CDE) is rare, but is increasingly diagnosed among those who have undergone colectomy. After colectomy, colonic-type bacterial flora including Clostridium difficile are able to colonize, and under the right circumstances, infect the small bowel. The reported mortality of CDE is high, likely due in part to the emergence of a virulent strain of Clostridium difficile, NAP1/BI/027. Physicians should have a high index of suspicion for CDE, particularly among patients with antibiotic exposure after colectomy. CASE DESCRIPTION/METHODS: A 50-year-old-woman with a previous history of Clostridium difficile infection (CDI) and colonic inertia status post total abdominal colectomy with ileorectal anastomosis three months prior presented with waves of left lower quadrant abdominal pain, abdominal distention, nausea, and vomiting. In the three weeks prior to admission, she completed courses of Amoxicillin and Trimethoprim-sulfamethoxazole for UTI. CT abdomen/pelvis with contrast showed 20 cm of circumferential thickening of the distal small bowel with associated free fluid and mesenteric inflammation proximal to unaffected ileorectal anastomosis. Laboratory evaluation was notable only for mild leukocytosis (12,000 cells/µL) with no bands. On admission, the patient had a nasogastric (NG) tube placed for abdominal decompression. A Bisacodyl suppository was prescribed, and the patient had a bowel movement that resulted positive for Clostridium difficile toxin DNA PCR. The patient was diagnosed with CDE. She was initially started on NG Vancomycin 150 mg every 6 hours for a first recurrence of CDI, which was then escalated to 500 mg every 6 hours with the addition of IV Metronidazole. This resulted in resolution of symptoms and ileus. DISCUSSION: Our patient had several CDE risk factors including a prior history of colectomy and recent antibiotic exposure. In addition to CDE risk factors, our patient also had two CDI risk factors - chronic acid suppression and previous history of CDI. Additional research is needed to determine if other typical CDI risk factors also play a role in the development of CDE. In patients with altered gastrointestinal anatomy or obstruction, it may be challenging to confirm the diagnosis using stool-based PCR toxin studies. Abdominal CT scan may be helpful in making the diagnosis. Much like our patient, previous studies have demonstrated circumferential edema and mesenteric stranding of the small bowel as common radiologic features of CDE.

S891 SUCCESSFUL TREATMENT OF INTESTINAL GRAFT‐VERSUS‐HOST DISEASE WITH FECAL MICROBIOTA TRANSPLANTATION

Background:Disruption of the intestinal microbiome has a negative influence on the outcome of allogeneic hematopoietic stem cell transplantation (HSCT). Decreased gut flora diversity with loss of commensals and pathobiont domination, is associated with an increased risk to develop graft‐versus‐host disease (GvHD). Fecal microbiota transplantation (FMT) has successfully been used to treat Clostridium difficile enteritis but the safety and efficacy of FMT in immunocompromised GvHD patients remains to be elucidated.Aims:1. To assess the safety and effectiveness of FMT as treatment for GvHD patients in a prospective, single‐arm pilot study2. To analyze the microbiome dynamics of GvHD patients receiving an FMTMethods:Fifteen patients with steroid‐refractory or steroid‐dependent intestinal GvHD received a single FMT from an unrelated, healthy donor via nasoduodenal infusion. Follow‐up included collection of blood and fecal samples prior to FMT and at 1, 4, 12 and 24 weeks after FMT as well as clinical follow‐up up to 6months.Results:FMT was well tolerated by all patients, there were no serious adverse events observed that could be attributed to FMT. Response evaluation at 4 weeks after FMT identified 11 participants with a complete response (CR), defined as resolution of all GvHD, without other interventions to alleviate symptoms. In 6 CR patients, the normalization of stool frequency and consistency was sustained throughout the whole period of follow‐up, with successful taper of immunosuppressants. Five other responders initially showed improvement of GvHD after FMT but relapsed upon prednisolone taper (CR/sf; complete responders with secondary failure). A durable response to FMT was associated with a better prognosis (Figure 1). Analysis of peripheral blood immune cell subsets did not reveal significant differences. Alpha diversity of fecal samples, analyzed by 16S ribosomal RNA sequencing, was low in patients pre‐FMT but improved upon response to treatment in CR and CR/sf patients. One week after FMT, the fecal microbial composition of CR patients resembled that of the donor the most, suggesting a better engraftment of fecal donor species in patients with persistent responses.Summary/Conclusion:This pilot study shows the potential of donor FMT to safely restore microbial diversity and improve symptoms of steroid‐refractory or steroid‐dependent GvHD patients. These encouraging data promote further investigation of this therapy in larger cohorts.image

A Rare Case of Clostridium difficile Enteritis: A Common Bug in an Uncommon Place

Clostridium difficile (CD), a bacterium responsible for causing 15%-25% of all cases of infectious diarrhea, is most commonly associated with infection of the colon. Rarely, though with increasing frequency, it has been noted to infect the small intestine in what is referred to as CD enteritis. We present the case of a patient who was diagnosed and treated for CD enteritis, review the pathophysiology behind the infection, and discuss the diagnostic and treatment options available to healthcare professionals.

Effects of stress ulcer prophylaxis in adult ICU patients receiving renal replacement therapy (Sup-Icu RENal, SIREN): Study protocol for a pre-planned observational study

BackgroundProton pump inhibitors are often used in critically ill patients to prevent gastrointestinal bleeding despite limited evidence for benefit. Patients with acute kidney injury requiring renal replacement therapy (RRT) are at high risk of gastrointestinal bleeding as (pre-)uremia induces coagulopathy through effects on platelets and coagulation cascades. No high-quality randomized clinical trials have previously assessed the benefits and harms of prophylactic proton pump inhibitor use in this high-risk population of adult critically ill patients.Methods/designAmong the 3350 patients included in the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) trial—an investigator-initiated international randomized clinical trial on prophylactic proton pump inhibitor versus placebo in acutely admitted adult ICU patients at risk of gastrointestinal bleeding—we will compare the benefits and harms of prophylactic use of proton pump inhibitor in patients in need of RRT versus those not requiring this treatment. We will determine the proportion of patients with clinically important bleeding, the proportion of patients with adverse events including pneumonia, Clostridium difficile enteritis, or acute myocardial ischemia in the ICU, as well as transfusion requirements. Moreover, 90 day and 365 day mortality post-randomization will be investigated. As a secondary analysis, we will examine the association between acute kidney injury and RRT during ICU stay and gastrointestinal bleeding.DiscussionWith the outlined predefined analysis, we will characterize the balance between the benefits and harms of stress ulcer prophylaxis in acutely admitted adult ICU patients in need of RRT, including the potential interaction of allocation to proton pump inhibitor versus placebo.Trial registrationClinicalTrials.gov, NCT02718261. Registered on 14 March 2016.

Necrotizing Clostridium difficile Enteritis Complicating Fulminant Colitis

Background:Clostridium difficile infections result from an imbalance in normal bacterial flora, allowing C. difficile bacteria overgrowth. Whereas such bacterial overgrowth is typically confined to the colon, there have been reports of an increasing prevalence of C. difficile infections involving the small bowel, with the majority of patients presenting with a history of partial or total colectomy. We present two rare cases of necrotizing C. difficile enteritis complicating fulminant C. difficile colitis. Case Presentations: A 74-year-old male presented with a two-week history of watery diarrhea and escalating abdominal pain without recent antibiotic use. Work-up was significant for leukocytosis, bandemia, lactic acidosis, and elevated creatinine. Initial diagnosis of C. difficile was treated with intravenous fluoroquinolone and metronidazole. He deteriorated and a total colectomy with small bowel resection was performed. Final pathology revealed pseudomembranous colitis with focal mucosal ischemia and pseudomembranous necrotizing enteritis. Post-operatively the patient's condition fluctuated, requiring re-initiation of antibiotics and vasopressor therapy; he ultimately recovered. A 72-year-old female presented with severe abdominal pain and septic shock two weeks after total abdominal colectomy with end ileostomy for severe C. difficile colitis. An exploratory laparotomy appeared normal, without an identifiable pathology source. Post-operatively she required vasopressor support and mechanical ventilation. She received intravenous metronidazole and vancomycin enemas. Clostridium difficile assays confirmed the diagnosis of relapsed pseudomembranous enteritis. Antibiotic therapy continued without further incident. Conclusion:Clostridium difficile enteritis presents a unique challenge because of its difficulty in diagnosis, a fact underscored by the high morbidity and mortality of small bowel of C. difficile infections. Clostridium difficile enteritis should be suspected in patients not improving after recent colectomy for C. difficile colitis. Continuation of antibiotics and total colectomy should be considered in patients with un-explained acute intra-abdominal pathology or persistent sepsis after colectomy for fulminant C. difficile colitis.

A Rare Case of Fulminant Clostridium difficile Enteritis in Patient With Ileal Pouch-Anal Anastamosis Causing Small Bowel Perforation: A Case Report With Review of Literature

Miss X is a 37 year old lady with a past medical history of familial polyposis with subsequent proctocolectomy with ileal pouch-anal anastomosis (IPAA). Patient presented to the hospital in labor and underwent a normal vaginal delivery. The patient then developed diarrohea with systemic signs including fevers, chills and lethargy. She was stabilized in the medical intensive care unit and was given intravenous fluid hydration with lactated ringers. Obstetrics team out infection of the genitourinary tract. Figure 1 shows the trend in stool output and white cell count. Clostridium difficile toxin in stool was found to be positive and the patient was started on oral vancomycin. Patient's abdominal distention worsened and she was taken to the operating room. She had small bowel perforation. About 20cm of bowel was resected and anastomosis completed. Patient tolerated the procedure well. She was continued on oral vancomycin and intravenous metronidazole. Clostridium Difficile Enteritis (CDE) in patients with IPAA has been reported in several case reports. However, CDE causing perforation in a patient with IPAA is very rare. Table 1 shows the reported case reports and studies of CDE in patients with IPAA between 2000 and 2016.Table: Table. Studies on CDE in patients with IPAA from 1990-2016. [Inflmmatory bowel disease (IBD), Ulcerative Colitis (UC), Per Oral (PO), Intravenous (IV)] *mean age, **median ageFigure: Trend of patient's clinical course during hospital course. [White Blood Cell Count (WBC)].

Clostridium difficile Enteritis in Patients Following Total Colectomy: A Genuine but Rare Clinical Entity

Clostridium difficile Enteritis in Patients Following Total Colectomy: A Genuine but Rare Clinical Entity

Clostridium difficile Enteritis: A Rare Disease Associated With High Mortality

Clostridium difficile is typically associated with colonic infection after recent antibiotic use; however, case reports have been increasing describing small bowel involvement. Many of these cases have been described in patients with colectomy with ileostomy who initially present with increased ostomy output. With the total incidence of C. difficile increasing and a high mortality rate associated with Clostridium difficile enteritis, early recognition is key to preventing mortality. A 75-year-old Caucasian female with history of ulcerative colitis who underwent a colectomy with ileostomy and a recent urinary tract infection treated with Keflex who presented with weakness, abdominal pain, and increased ostomy output. Lab work showed leukocytosis of 35,000 cells/mm3 and a positive C. difficile PCR. Intravenous metronidazole and oral vancomycin was started, but her condition worsened. She was transitioned to the ICU. After a day of worsening epigastric pain, imaging obtained demonstrated free air. Exploratory laparotomy revealed gastric perforation, which was repaired. She required another operation after developing an enterocutaneous fistula. Post-operatively she developed respiratory failure. On day nineteen, she developed a low-grade fever and intravenous vancomycin was started. She then developed an abdominal abscess, which required drainage by interventional radiology. Her gastric leak persisted but it was felt she would not tolerate surgery. She ultimately expired soon after. Overall C. difficile infection overall has been associated with mortality rates of 6.9% at 30 days and 16.7% at one year. Initial estimates of C. difficile enteritis (CDE) mortality were as high as 66%. With the increasing number of reported cases, the mortality rate may be closer to that of 25.3%-32.1%. Clinically CDE can present from high-output ileostomy to fulminant enteritis. Most cases are confined to the colon; however, the organism has been isolated in jejunal segments at autopsy, suggesting the small bowel may act as a reservoir for the bacteria. There have also been case reports of colonic metaplasia occurring in the small bowel after colectomy. Alterations in the small bowel anatomy to resemble large bowel may predispose patients to CDE. Bile salts at low concentrations stimulate proliferation of the colonic epithelium and are involved in the regulation of colonic mucosal growth by upregulating Transforming Growth Factor-β. After colectomy small bowel may be exposed to bile salts for longer periods of time therefore possibly increasing colonic metaplasia and growth.Treatment options are similar to that of C. difficile colitis with vancomycin or metronidazole being first line, but early recognition is key to decreasing mortality and morbidity.Figure 1Figure 2

A Rare Case of Clostridium difficile Enteritis and Small Bowel Obstruction

There have been less than one-hundred reported cases of Clostridium difficile enteritis, demonstrating the rarity of our case. To date, there is no consensus on the treatment of C.difficile enteritis. Understanding the cause for C.diff enteritis and initial treatment is important to quickly identify and prevent potential associated complications.Figure 1Figure 2A sixty-four year-old male with familial adenomatosis polyposis s/p colectomy and J-pouch presented with recurrent gastrointestinal bleeding, abdominal pain, and diarrhea. A recent EGD and RBC scan failed to identify a bleeding source. An abdominal/pelvis CT performed two days prior to admission was significant for small bowel distention. Repeat abdominal/pelvis CT found enteritis of the J-pouch and fluid-filled bowel loops. A C. difficile antigen test was positive. Initial treatment with oral metronidazole was unsuccessful. Antibiotics were changed to intravenous metronidazole and oral vancomycin and finally oral vancomycin for two weeks. The diarrhea improved and repeat C.difficile antigen testing was negative. Following treatment, the abdominal pain and nausea persisted and the patient was unable to tolerate a colonoscopy prep. An abdominal x-ray revealed multiple loops of small bowel with air-fluid levels of discordant heights. Due to concerns for a small bowel obstruction an NG tube was inserted. An exploratory laparotomy with lysis of adhesions and pouch endoscopy were performed revealing an internal closed loop obstruction and a distal pouch obstruction due to anal stenosis, which was dilated. The constipation continued following the operation and a rectal tube was placed. A repeat enteroscopy two weeks after the laparotomy found an ileoanal stricture above the J-pouch and was dilated. Afterwards, the bowel obstruction and patient's condition improved. This case illustrates the delay in diagnosis of the cause of a small bowel obstruction following C.difficile enteritis leading to an extended hospital stay. This case raises the question of whether the stricture may have have been prevented with either earlier or more aggressive antibiotic therapy. Further, with no consensus for treatment of C.difficile enteritis, is aggressive initial antibiotic therapy necessary as compared to standard treatment for C.difficile colitis?

Two Patients with Fulminant Clostridium difficile Enteritis Who Had Not Undergone Total Colectomy: A Case Series and Review of the Literature.

Introduction. Clostridium difficile is the most common cause of healthcare associated infectious diarrhea, and its most common clinical manifestation is pseudomembranous colitis. Small bowel enteritis is reported infrequently in the literature and typically occurs only in patients who have undergone ileal pouch anastomosis due to inflammatory bowel disease or total abdominal colectomy for other reasons. Presentation of Cases. We report here two cases in which patients developed small bowel C. difficile enteritis in the absence of these underlying conditions. Discussion. Neither patient had underlying inflammatory bowel disease and both had a significant amount of colon remaining. Conclusion. These two cases demonstrate that small bowel C. difficile enteritis should be included in the differential diagnosis of patients on antibiotic therapy who demonstrate signs and symptoms of worsening abdominal disease during their postoperative course, even if they lack the major predisposing factors of inflammatory bowel disease or history of total colectomy.

P-109 YI Risk Factors and Outcomes of Clostridium Difficile Enteritis in Patients with Ileostomy

P-109 YI Risk Factors and Outcomes of Clostridium Difficile Enteritis in Patients with Ileostomy

A Case of Recurrent Clostridium difficile Enteritis Treated With Fecal Microbiota Transplant

Introduction:Clostridium difficile enteritis (CDE) is a rare but increasingly recognized disease. Risk factors for CDE include gastrointestinal surgery, antibiotic use, and immunosuppression. Case Report: A 38-year-old man with autoimmune alopecia presented with bloody diarrhea and severe abdominal pain. He had 4 self-limited episodes of mild abdominal pain and non-bloody diarrhea in the past 2 years, and had completed several courses of antibiotics for presumed gastroenteritis. He denied NSAID use. On exam, he had diffuse abdominal tenderness with voluntary guarding. Laboratory evaluation revealed WBCs of 15.8 x 10ˆ9/L and abdominal/pelvic CT showed thickened small bowel loops in the right lower quadrant with free fluid and soft tissue stranding. Colonoscopy revealed a normal colon and a 10-cm segment of erythematous mucosa in the terminal ileum with normal histology. Stool cultures were negative, but C. difficile PCR returned positive. He improved on metronidazole and was discharged. Three weeks later, he presented with worsening abdominal pain and diarrhea, WBCs 18.1 x 10ˆ9/L, positive C. difficile PCR, and interval worsening of diffuse terminal ileal inflammation on CT scan. He improved rapidly on oral vancomycin. MRE/MRA on hospital day 3 was negative for large vessel vasculitis and showed resolution of the ileal thickening seen on admission CT. Work-up also included normal complement levels, HIV and TB testing, and autoimmune serologies. Repeat colonoscopy and small bowel enteroscopy were normal, and capsule endoscopy showed slight ileal patchy erythema. One month after completing his vancomycin taper, he again presented with abdominal symptoms, WBCs of 23 x 10ˆ9/L, circumferential thickening of the entire ileum on CT, and positive C. difficile PCR. He improved on IV metrondiazole and oral vancomycin, which was continued until 3 days prior to outpatient fecal microbiota transplant (FMT) via colonoscopy. On the day of the procedure, he endorsed mild abdominal pain. Terminal ileum at time of FMT appeared mildly erythematous. After FMT, he experienced rapid and complete resolution of abdominal pain and remained symptom free 6 weeks later. Discussion: It is hypothesized that CDE develops from intestinal metaplasia and intestinal flora changes triggered by prior gastrointestinal surgery, chronic immunosuppression, or antibiotic exposure. While CDE has been reported in patients after colectomy, it is exceptionally rare in immunecompetent patients with no previous bowel surgery. This case demonstrates a rare case of CDE in a patient without predisposing conditions. This case also highlights the utility of FMT in recurrent C. difficile infection and represents the first case of CDE treated by FMT. Disclosure - Dr. Colleen Kelly - Site investigator for a clinical trial for Seres Health. Drs Freeman, Mao, Shah have no relevant financial relationships to disclose.

Risk of Proton Pump Inhibitor–Induced Mild Hyponatremia in Older Adults

To the Editor: The incidence of hyponatremia, a side effect that can result from using proton pump inhibitors (PPIs), is unknown in elderly adults. A prospective clinical study of individuals with suspected drug-induced moderate hyponatremia was recently conducted; 47% of the population was being treated with PPIs, indicating that the risk of PPI-induced hyponatremia is significant in elderly adults (≥65).1 This was a retrospective study. The main objective was to determine the incidence of hyponatremia in the elderly population being treated with PPIs; other objectives were to determine the odds ratio of PPI inducing hyponatremia, the relationship between PPI dose and occurrence of hyponatremia, and risk of hyponatremia in association with other medications. The incidence of hyponatremia in individuals who had been taking PPIs for at least 1 year was compared with that in a control group of individuals who had not been exposed to PPIs. Hyponatremia risk factors, except drugs known to induce hyponatremia, were exclusion criteria. The study included individuals in a unit of a general hospital admitted during 2011. Of 302 individuals analyzed, 145 were included. Twenty-four (16.6%) had moderate hyponatremia, and 48 (33.1%) had been taking PPIs for longer than 1 year, 31.3% of whom (95% confidence interval (CI) = 18.7–46.3%) had moderate hyponatremia, versus 9.3% (95% CI = 14.3–16.9%) in the rest of the population (OR = 4.4, 95% CI = 1.8–11.1, P = .001). The relationship between dose and occurrence of hyponatremia was not significant (coefficient of determination = 0.05, P = .74). Individuals taking PPIs and tramadol had a significantly higher risk of having hyponatremia than those taking neither (OR = 7.7, 95% CI = 1.9–31.2). Table 1 describes the relationship between hyponatremia, medication use, and potentiation in association with PPIs. The results are expressed as incidence of hyponatremia and the number of affected subjects for each drug or each drug combined with PPIs. In the literature, cases of hyponatremia in conjunction with PPI use have been reported without reporting the incidence rate.2 Moreover, hyponatremia is described as a rare event in PPI product information (<0.1%).3 Between 18.7% and 46.3% of elderly PPI users had hyponatremia in the current study. This study demonstrates that the chronic use of PPIs increases the risk of hyponatremia in older adults. This could be a result of their antidiuretic activity or the potentiation of the reactive antidiuretic hormone secretion.2 The association between PPIs and tramadol also appears to potentiate the risk of hyponatremia. Risk of hyponatremia with tramadol has been described in the literature.4 This combination is frequently administered to elderly adults and requires further study. Drugs are an underestimated cause of hyponatremia in elderly adults.5 Moderate hyponatremia significantly increases morbidity, for example, by increasing the risk of falls and fractures, and increases the risk of osteoporosis. It is also a predictor of death, myocardial infarction, and longer duration of hospitalization in elderly adults.6, 7 The effectiveness of PPIs and their safety has led to their widespread use. The known potential consequences of chronic use of PPIs include hypergastrinemia, enterochromaffin-like cell hyperplasia, and parietal cell hypertrophy, which causes rebound acid hypersecretion. PPI use is also a risk factor for Clostridium difficile enteritis, pneumonia, nutritional deficiencies, and interactions with antiplatelet agents.8 Although PPI moderate hyponatremia is an unknown effect, more fractures are being reported. It may be that episodes of hyponatremia potentiate these events by causing attention deficits, with a higher incidence of falls causing fractures, which adds to the direct effect on bone remodeling.9, 10 Thus, the literature suggests a need for a benefit: risk balance assessment amended by the latest knowledge of pharmacovigilance, and the current study confirms the potential adverse effects of PPI use in the elderly population. PPIs are commonly administered to elderly adults: 33% in the current study. The extensive use of PPIs in elderly adults is often the result of a lack of therapeutic reevaluation or requests from the individual to avoid treatment interruption. PPIs must be discontinued when the risk-benefit balance becomes unfavorable. Reassessment of the prescription is useful, particularly because a recent study has shown that hyponatremia is reversible; the reduction of drugs that may induce hyponatremia was associated with significant clinical improvement.1 Future prospective studies that include follow-up laboratory results for comparisons of pre- and post-PPI therapy would be optimal and informative. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: Buon, Peyro Saint Paul: acquisition of subjects and data, analysis and interpretation of data, and preparation of manuscript. Gaillard, Fedrizzi, Mosquet, Coquerel: analysis and interpretation of data, preparation of manuscript. Martin: acquisition of subjects, analysis and interpretation of data, and preparation of manuscript. Sponsor's Role: No sponsor.

Poor Outcomes in Clostridium difficile Enteritis is Associated with Low Vitamin D Levels

Poor Outcomes in Clostridium difficile Enteritis is Associated with Low Vitamin D Levels

Clostridium Difficile of the Ileum Following Total Abdominal Colectomy, With or Without Proctectomy

Clostridium difficile enteritis is considered a rare entity, although recent data suggest a significant increase in prevalence and incidence. There is paucity of data evaluating risk factors of C difficile enteritis following total colectomy. The aim of this study was to determine the incidence and risk factors of C difficile enteritis for patients who had undergone total abdominal colectomy with or without proctectomy. This study involves a retrospective chart review of 310 patients. Univariate analysis was performed on potential risk factors (p ≤ 0.05) with the use of a logistic regression model, and a Fisher exact test was used for variables that had no occurrences of C difficile. These groups of variables were then examined in a multiple variate setting with stepwise logistic regression analysis. This study was conducted at a tertiary referral center. A data analysis was performed on patients who had undergone total abdominal colectomy with or without proctectomy who were tested for C difficile of the ileum. Twenty-two of 137 patients that were tested (16%) were positive for C difficile of the ileum. Univariate analysis of known risk factors for C difficile demonstrated that black race was a protective factor against C difficile (p = 0.016). The multivariate analysis demonstrated that emergency surgery (p = 0.035), race (p = 0.003), and increasing age by decade (p = 0.033) were risk factors for C difficile. This study was limited by the small patient sample, and it was not a randomized trial. Black race is protective, and whites are 4 times more likely to acquire C difficile of the ileum after undergoing a total abdominal colectomy with or without proctectomy. The data also demonstrated that an increased age by a decade and emergency surgery are risk factors for C difficile enteritis, whereas the described risk factors of C difficile of the colon and type of colon surgery do not appear to influence the risk of C difficile of the ileum.