Vancomycin Enemas Research Articles

Clostridium difficile infection secondary to ileostomy closure

Protective ileostomy may be a risk factor for the development of Clostridium difficile (CD) infection (CDI). In the postoperative period signs of CDI may be particularly difficult to differentiate from intra-abdominal sepsis. Presented here are 2 cases that developed CDI after ileostomy reversal. Two patients who underwent low anterior resections after neoadjuvant chemoradiation with protective ileostomy developed fever, leukocytosis and elevated serum C-reactive protein (CRP) levels. The first patient also had negative CD stool toxins and his signs were so severe that he underwent a negative diagnostic laparoscopy and re-creation of ileostomy. The second patient who presented in a similar fashion was more fortunate in that her CD stool toxin was positive and she was treated successfully with oral vancomycin. CDI after ileostomy reversal after low anterior resection can be difficult to diagnose. In the first patient, the situation was so misleading that diagnostic laparoscopy was required. Outcome was eventually favorable in both cases. CDI must be high on the list of differential diagnoses for febrile patients with a leukocytosis and elevated CRP level even in the setting of negative CD stool toxins. Prophylactic intravenous metronidazole and/or vancomycin enemas should be considered prior to colorectal surgery when a protective ileostomy is likely.

S1762 An Atypical Presentation of Fulminant Clostridioides difficile Colitis Without Diarrhea

INTRODUCTION: Clostridioides difficile infection (CDI) occurs mostly after antibiotics use and presents almost invariably with watery diarrhea. Here, we described an unusual presentation of fulminant CDI in a middle aged woman who was admitted with altered mental status and ileus but no diarrhea. CASE DESCRIPTION/METHODS: A 62-year-old woman with a history of schizophrenia was admitted to inpatient psychiatry for treatment of schizophrenia. On hospital day 47, she was found to be severely somnolent with fecal incontinence. Vital signs were notable for tachycardia and fevers. Physical exam was remarkable for abdominal distension, tympany with hypoactive bowel sounds, and diffuse abdominal tenderness. Laboratory revealed marked leukocytosis of white blood cells (WBC) 51 × 109 cells/L, lactate 3.66 mg/dL, and acute kidney injury with creatinine 1.4 mg/dL. Abdomen and pelvis CT showed proctocolitis and distension of rectum and left colon along with significant stool burden. The patient was initially started on broad spectrum antibiotics for severe sepsis of unknown origin however without significant improvement. She was managed for constipation with oral bowel regimen, tap water enemas, suppositories, and manual disimpactions. Given persistent leukocytosis and overflow diarrhea, stool C. difficile toxin was checked and resulted positive. The patient was subsequently treated for fulminant CDI with oral vancomycin, vancomycin enemas and intravenous metronidazole. After the 14-day course of antibiotics, her abdominal pain and distension resolved and leukocyte count normalized. DISCUSSION: The most common symptom of CDI is watery diarrhea which is often associated with abdominal pain, fever, and leukocytosis. Unique features in our case include lack of diarrhea, a significantly high WBC count and no history of recent antibiotics use. The abdominal pain and distention were attributed to stool impaction. Persistent high WBC, minimal response to bowel regimen, and ileus led to further investigation with C. difficile stool test in our patient. Symptoms resolved after proper treatment of CDI. It was reported that CDI can present acutely as ileus with constipation and absence of diarrhea [1]. This is due to pooling of secretions in dilated and atonic colon. These patients are at high risk to progress rapidly to toxic megacolon and perforation if not treated promptly. CDI should be considered in the context of unexplained severe sepsis with high WBC even without diarrhea.

Clostridioides difficile associated peritonitis in peritoneal dialysis patients \u2013 a case series based review of an under-recognized entity with therapeutic challenges

BackgroundInitial presentation of peritoneal dialysis associated infectious peritonitis can be clinically indistinguishable from Clostridioides difficile infection (CDI) and both may demonstrate a cloudy dialysate. Empiric treatment of the former entails use of 3rd-generation cephalosporins, which could worsen CDI. We present a logical management approach of this clinical scenario providing examples of two cases with CDI associated peritonitis of varying severity where the initial picture was concerning for peritonitis and treatment for CDI resulted in successful cure.Case presentationA 73-year-old male with ESRD managed with PD presented with fever, abdominal pain, leukocytosis and significant diarrhea. Cell count of the peritoneal dialysis effluent revealed 1050 WBCs/mm3 with 71% neutrophils. C. difficile PCR on the stool was positive. Patient was started on intra-peritoneal (IP) cefepime and vancomycin for treatment of the peritonitis and intravenous (IV) metronidazole and oral vancomycin for treatment of the C. difficile colitis but worsened. PD fluid culture showed no growth. He responded well to IV tigecycline, oral vancomycin and vancomycin enemas. Similarly, a 55-year-old male with ESRD with PD developed acute diarrhea and on the third day noted a cloudy effluent from his dialysis catheter. PD fluid analysis showed 1450 WBCs/mm3 with 49% neutrophils. IP cefepime and vancomycin were initiated. CT of the abdomen showed rectosigmoid colitis. C. difficile PCR on the stool was positive. IP cefepime and vancomycin were promptly discontinued. Treatment with oral vancomycin 125 mg every six hours and IV Tigecycline was initiated. PD fluid culture produced no growth. PD catheter was retained.ConclusionsIn patients presenting with diarrhea with risk factors for CDI, traditional empiric treatment of PD peritonitis may need to be reexamined as they could have detrimental effects on CDI course and patient outcomes.

Role of Surgery in Clostridium difficile Infection.

Clostridium (reclassified as " Clostridioides ") difficile infection (CDI) occurs as a chronic or an acute illness with intensity varying from mild to severe. Although most cases of CDI can be managed with antibiotics and supportive care, when the patient presents with fulminant disease, the early decision to perform surgery is imperative for survival. The current standard of care is the subtotal colectomy. However, loop ileostomy with vancomycin enemas delivered into the colonic mucosa has been described as a viable option on selected patients.

2289 Clostridioides difficile-Associated Hemolytic Uremic Syndrome After Orthotopic Liver Transplantation

INTRODUCTION: Clostridium Difficile infection (CDI) has previously been reported as a rare cause of possible Hemolytic Uremic Syndrome (HUS) in both adults and children. We present a unique case of CDI related HUS in a patient post orthotopic liver transplantation (OLT). CASE DESCRIPTION/METHODS: A 40-year-old African American male presented with acute decompensation of alcoholic cirrhosis. After evaluation, the patient underwent successful OLT. Post-transplant course was complicated by post-operative bleeding requiring multiple exploratory laparotomies. Patient developed new-onset acute renal failure post transplantation requiring hemodialysis and prolonged courses of antibiotics. On post op day 15, patient developed diarrhea and tested positive for CDI. Physical examination was significant for jaundice, multiple ecchymoses, and a large abdominal wound without signs of excessive erythema. Laboratory data at that time showed hemoglobin drop to 5 g/dL from 8.7 g/dL, thrombocytopenia with a drop in platelets from 282 × 103/uL to 15 × 103/uL, and blood smear consistent with presence of schistocytes raising the concern for a hemolytic process. Lactate dehydrogenase (LDH) was greater than 6450 U/L, haptoglobin was less than 6 mg/dL, and reticulocytes were elevated at 8.06%. ADAMSTS-13 resulted at 26% with a negative ADMASTS-13 antibody screen suggestive against thrombotic thrombocytopenic purpura. Serotonin release assay antibodies and heparin induced thrombocytopenia antibodies were not present. A diagnosis HUS secondary to CDI was made, and the patient was started on treatment for severe CDI with oral vancomycin, vancomycin enemas, and intravenous metronidazole. The patient also underwent emergent plasma exchange receiving 4 treatments, blood transfusions, and prednisone therapy (1 mg/kg). The patient had improvement in his hemoglobin and platelets following therapy and eventual resolution of diarrhea. His mental status as well returned to baseline. Patient’s hospital course was later complicated by aright hemicolectomy, end ileostomy secondary to toxic megacolon, and pathology was consistent with pseudomembranous colitis.His renal function did not recover and he was declared end-stage renal disease. DISCUSSION: CDI related HUS is exceedingly rare. The pathogenesis of CDI related HUS has not been well defined. To our knowledge, this is the first case of CDI related HUS in a patient post OLT. It is important for gastroenterologists and hepatologists to be aware that although rare, CDI is a possible cause of HUS.

Vancomycin Enema in the Treatment of Clostridium difficile Infection.

Background: Current guidelines for the treatment of Clostridium difficile infections (CDIs) recommend vancomycin enemas for patients with adynamic ileus. There is significant variability in guideline recommendations for vancomycin dose and enema volume and whether a retention enema should be used. The most recent (2017) guidelines from the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America recommend rectal instillation of 500 mg of vancomycin in 100 mL of physiologic saline every 6 hours as a retention enema. Methods: Published studies regarding vancomycin enema use in CDI (1990-present) were reviewed to compare drug dose, volume, and whether a retention enema was used in order to determine the efficacy and make recommendations for optimal dosing. Results: Case series with higher vancomycin dose, higher enema volume, and use of retention enema demonstrated greater efficacy. Use of smaller volumes and lower doses (100 mL; 125-250 mg q 6 hours) demonstrated no efficacy of intracolonic vancomycin. Conclusion: We recommend revision of the current CDI guideline recommendations for patients with adynamic ileus to the following: Vancomycin per rectum (500 mg in a volume of 500 mL q 6 hours) by retention enema (18F Foley catheter with 30-cc balloon inserted into the rectum, balloon inflated, solution instilled, and catheter clamped for 60 minutes) for optimal efficacy.

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.

Efficacy of Fecal Microbiota Transplant (FMT) In Severe/Complicated Clostridium difficile Infection (CDI): A Case Series

Introduction: There is significant data that establishes the efficacy and safety of Fecal Microbiota Transplant (FMT) in recurrent Clostridium difficile infection (CDI), however there is limited data on the success of FMT in severe/complicated CDI. We describe a case series of 4 patients at our tertiary care center who underwent FMT in the ICU for fulminant CDI refractory to antimicrobial therapy. Case Description: Our study cohort included 2 Caucasian,1 African American and 1 Indian patient. All 4 of them were admitted to the ICU for complicated CDI. 2 of these patients were in septic shock from CDI colitis. 1 had end organ failure with AKI requiring dialysis and the other had severe sepsis with respiratory failure. CDI was confirmed by stool PCR.? All 4 patients were on antibiotics for CDI with intravenous Metronidazole and oral Vancomycin.Two patients also received Vancomycin enema and 1 patient was on Fidaxomicin.In each case, CDI was refractory to treatment with adequate antibiotic therapy with unchanged/worsening clinical status. Therefore, FMT was considered as the next step. The donor stool was obtained from Open Biome. 3 of them underwent FMT via NG Tube consisting of 100 cc of slurry. One patient received FMT via PEG tube .After FMT, 2 of them were continued on oral Vancomycin; 1 patient continued both IV Metronidazole and oral Vancomycin. Antibiotics were discontinued on one patient.?After FMT, all 4 had resolution of symptoms with marked improvement of diarrhea and abdominal pain. The average time interval between FMT and improvement of symptoms was 5.25 days (2-8). One patient had recurrent CDI after 3 months which was attributed to the use of antibiotics for COPD.Table: No Caption availableDiscussion: Severe/complicated CDI is defined by the 2013 ACG guidelines as: admission to ICU for CDI, hypotension with or without use of vasopressors, fever ≥38.5 °C, ileus, significant abdominal distention, WBC ≥ 35 000 cells/mm3, lactate levels >2.2 mmol/L or end organ failure.Complicated CDI is challenging often requiring prolonged ICU stay. Colectomy is the standard of care in severe cases; however mortality rates are as high as 35-57 %.Often many patients are poor surgical candidates due to significant comorbidities such as shock, respiratory failure and advanced age> 80. Our success with FMT in the critically ill suggests that FMT should be considered judiciously earlier in the disease course for early symptoms resolution and avoidance of the more invasive colectomy.

Eradication of Persistent C. difficile Infection (CDI) in Pediatric Patients Requiring Complex Medical Care: Experience with Use of Golytely and Vancomycin Enema

Introduction: C. difficile infections is a potentially lethal condition and also the leading cause of nosocomial infections affecting care of patients with complex needs in post-acute care facilities. Eradication of C. diff is very important to prevent outbreaks of nosocomial infection but has been difficult in some patients because of emergence of a virulent strain resistant to multiple antibiotics. There is paucity of data on management of persistent CDI in pediatric post—acute care facilities; most of the data pertain to geriatric facilities. We describe our experience with use of Golytely (polyethylene glycol 3350 and electrolyte) followed by vancomycin enema to eradicate C. dif from patients with persistently positive C. diff after standard treatment. Methods: We performed a retrospective review of records of patients with persistent CDI treated with Golytely at our facility over period of one year (7/1/12-6/30/13). The initial stool test for C. diff was done in symptomatic patients; eradication was defined as 3 consecutive negative stool tests for C. diff at weekly intervals after completion of treatment. Standard treatment included enteric metronidazole (M) 30 mg/kg/day for 10-14 days. Enteric vancomycin (V) (40-50 mg/kg/day for 10-14 days) was given if M failed. In some patients, both, M and V were given if V alone failed. All patients were given probiotics. Patients with persistent CDI after above treatment were given Golytely at 20 cc/kg/hour via gastrostomy tube until the patients passed clear stool followed by 2 weeks of vancomycin enema (VE). Results: Golytely + vancomycin enema (G+VE) treatment was given 11 times in 7 patients (age 4 ½ yr. - 13 ½ yr.; 3M:4F; 1 patient received Golytely three times, and 2 patients received twice) with persistent CDI. Of these 7 patients, C. diff was successfully eradicated from 6 patients. One patient who did not respond received G+VE three times (3 months apart) and each time stool for C. diff became positive three weeks after treatment in third stool sample. In two patients who received G+VE twice, C. diff was eradicated successfully first time but recurred after antibiotic use and was successfully treated with G+VE second time also. Conclusion: Persistent CDI is an important problem in pediatric patients receiving complex medical care. Treatment modality consisting of combination of Golytely for 12 hours and vancomycin enema for 2 weeks results in successful eradication of C. diff from the patients with persistent CDI.

The Surgical Management of Complicated Clostridium Difficile Infection: Alternatives to Colectomy.

Clostridium difficile is the most common nosocomial infection in the United States. There is a subset of patients for whom medical therapy fails or who progress rapidly to the development of complicated disease, often marked by critical systemic illness. Patients with complicated Clostridium difficile infection (CDI) who progress or fail to improve benefit from surgery. This focused review highlights the importance of early surgical consultation for patients with complicated CDI, as well as emerging surgical therapy that does not involve resection of the colon but rather the creation of a loop ileostomy with colonic lavage, followed by antegrade vancomycin enemas into the colon during the post-operative period.

Antibiotic Regimen after a Total Abdominal Colectomy with Ileostomy for Fulminant Clostridium difficile Colitis: A Multi-Institutional Study.

Fulminant Clostridium difficile colitis (fCDC) is a highly lethal disease with mortality rates ranging between 12% and 80%. Although often these patients require a total abdominal colectomy (TAC) with ileostomy, there is no established management protocol for post-operative antibiotics. In this study we aim to make some recommendations for post-operative antibiotic usage, while describing the practice across different institutions. Multi-institutional retrospective case series including fCDC patients who underwent a TAC between January 1, 2007, and June 30, 2012. We first analyzed the complete cohort and consecutively performed a survivor analysis, comparing different antibiotic regimens. Additionally we stratified by time interval (antibiotics for ≤7 d, or ≥8 d). Primary outcome was in-hospital mortality. Additional secondary outcomes included hospital length of stay (HLOS), ICU LOS, number of ventilator-free days, and occurrence of intra-abdominal complications (proctitis, abscess, sepsis, etc.). A total of 100 fCDC patients that underwent a TAC were included across five institutions. Four different antibiotic regimens were compared; A (metronidazole IV+vancomycin PO), B (metronidazole IV), C (metronidazole IV+vanco PO and PR), and D (metronidazole IV+vancomycin PR). The combination of IV metronidazole with or without PO vancomycin showed superior outcomes in terms of a shorter ICU length of stay and more ventilator-free days. However, when comparing metronidazole alone vs. metronidazole and any combination of vancomycin, no significant differences were found. Neither the addition of vancomycin enema, nor the time interval changed outcomes. Patients, after a TAC for fCDC, may be placed on either IV metronidazole or PO vancomycin depending upon local antibiograms, and proctitis may be treated with the addition of a vancomycin enema (PR). There was no data to support routine treatment of more than 7 d.

Vancomycin Enemas as Adjunctive Therapy for Clostridium difficile Infection.

BackgroundFor severe, complicated Clostridium difficile infection (CDI), concomitant treatment with IV metronidazole and oral vancomycin is usually prescribed. Sometimes vancomycin per rectum (VPR) is added to increase colonic drug delivery. Our purpose was to examine clinical outcomes of patients with CDI treated with VPR and compare results to a matched control group.MethodsThis was a retrospective case-control study in a setting of tertiary-care ICU on diarrhea patients with a positive toxin test for C. difficile. We identified all ICU patients prescribed VPR from January 2003 to December 2013. The dose of VPR mixed in 100 cc of tap water ranged from 125 to 250 mg Q 6 - 8 hours. All patients had diarrhea and a positive test for C. difficile toxin. Included patients received ≥ 4 doses of VPR. The primary outcome was the combined endpoint of colon surgery or death. We matched VPR cases 1:2 with CDI controls that had identical APACHE II scores.ResultsWe identified 24 CDI patients who received VPR and met inclusion criteria: 11 male, mean age 61.8 ± 15.9 years. All patients received concomitant CDI therapy. Four patients (16.7%) required colectomy, and overall mortality was 45.8%. For the 48 controls, need for surgery was identical (16.7%; P = 1.00). The mortality rate also did not differ (41.7%; P = 0.74). For the combined outcome of surgery or death, the rate was 45.8% for the controls and 50.0% for the VPR group (P = 0.73).ConclusionIn a case-control study, the use of VPR was not demonstrated to reduce the need for colectomy or decrease mortality. Based on our modest sample size and failure to show efficacy, we cannot strongly advocate for the use of VPR.

Outcomes for Severe Complicated Clostridium difficile Infection Treated with Vancomycin Enemas

Introduction: The prevalence of Clostridium difficile infection (CDI) is increasing. Serious, complicated infections have been linked to a virulent strain (BI/NAP1), which produces elevated levels of toxin and can lead to colectomy or death. For these infections, standard of care is now concomitant treatment with IV metronidazole (IVM) and per oral vancomycin (POV). Some institutions use add-on therapy with vancomycin per rectum (VPR) to increase colonic drug delivery when there is a concern about delayed transit. Our purpose was to look at clinical outcomes of consecutive patients with CDI treated with VPR at our hospital. Methods: Using pharmacy records and manual chart review, we identified inpatients prescribed VPR from 1/2003 to 12/2013. Included patients had diarrhea, a positive stool test for Clostridium difficile toxin by ELISA, and no alternative cause for symptoms. Patients were required to have been in the ICU at the initiation of treatment and to have received ≥4 doses of VPR. Patients were followed to discharge or death. Results: We identified 43 CDI patients who received VPR during the study period. We excluded 18 patients because they did not receive ≥4 doses of VPR and 1 patient who received VPR after colonic surgery. There were 11 males and 13 females, mean age was 61.8±15.9 years (range: 21-93). The dose of VPR (IV solution mixed in 100 cc of tap water) ranged from 125 to 250 mg Q 6-8 hrs. Most patients received concomitant therapy with POV (n=17) and/or IVM (n=20). Four patients (16.7%) underwent colectomy and 3 died post-op. Mortality was 11/24 (45.8%) including the 3 post-op deaths. The mean number of doses of VPR in those who survived versus died was 22.3±6.9 vs. 19.3±19.4 (P=0.62). Similarly, there were no significant differences (all P>0.05) in age (64.5±16.7 vs. 59.1±15.3 years), WBC (24.6±11.5 vs. 25.7±17.9K), or interval rise in creatinine (91.6% vs. 100%) between those who survived versus died or those who survived versus the combined endpoint of surgery/death. There was notably a shorter median time interval between initiation of CDI treatment and initiation of VPR for those who survived and avoided surgery (3.5 days; IQR 1-15.25 vs. 8.5 days; IQR 2-19.5), but this was not statistically significant (P=0.47). Conclusion: In our study, the largest case series reported to date on the use of VPR for severe, complicated CDI, 50.0% of patients ultimately died or had a colectomy. Based on our modest sample size and high rate of morbidity and mortality we cannot strongly advocate for the use of VPR at this time. It appeared that earlier initiation of VPR may be beneficial. Controlled trials are needed to better assess this therapy.

Clostridium colitis: challenges in diagnosis and treatment

Clostridium difficile infection (CDI) has been reported to occur with increasing frequency and with more severe presentations being encountered. This article presents data from The Alfred Hospital highlighting the increased incidence, the increased severity and the broader clinical presentations observed. A case series highlights a variety of clinical scenarios that provided diagnostic and management challenges. We additionally describe a novel form of treatment for fulminant colitis. A retrospective review of C. difficile toxin (CDT)-positive and culture-positive cases was performed at The Alfred Hospital (2010-2012). Six cases are then presented as a case series to highlight the broad and atypical types of presentations one may encounter. Finally, a novel method for managing fulminant colitis operatively is presented. A fourfold increase in cases of toxin-positive and culture-positive cases was noted over the initial 14 months of the period of analysis, the rate of cases detected then plateaued. This increase could not be explained by increased testing being undertaken. It is also not associated with increased usage of antibiotics nor with increased patient numbers being treated. CDI can present in various clinical forms. In our hospital, the number of cases of toxin-positive and culture-positive detection is increasing. A low threshold is required to identify and adequately treat patients with CDI. Fulminant colitis can be managed successfully with the creation of a diverting loop ileostomy, colonic washout and subsequent antegrade colonic vancomycin enemas.

Colonic decompression and direct intraluminal medical therapy forClostridium difficile-associated megacolon using a tube placed endoscopically in the proximal colon

Urgent colectomy for severe Clostridium difficile infection can be associated with increased morbidity and mortality. We aimed to use endoscopic methods for treatment. We describe a technique of placing an intracolonic tube facilitating decompression and direct delivery of vancomycin to the proximal colon along with enemas on a regular and frequent basis that may not be possible with vancomycin enemas alone. Successful resolution of the C. difficile infection and avoidance of surgery. While further long-term evaluation is required, our initial results have shown it to be effective in treating select patients with recalcitrant Clostridium difficile-associated megacolon.

Intracolonic Vancomycin for Severe Clostridium difficile Colitis

Clostridium difficile colitis is associated with increased age, antibiotic usage, and hospitalization. Severe C. difficile colitis refractory to medical therapy may require surgical intervention including subtotal colectomy. We initiated an adjuvant intracolonic vancomycin (ICV) enema protocol for inpatients with severe C. difficile colitis and compared the response to this therapy in patients from the community and nursing homes. A single-hospital, retrospective chart review was done on 47 consecutive patients with C. difficile colitis treated with ICV (1 g/500 mL normal saline q6h) from January 2007 through October 2009. The proportions of patients with the outcomes of response to the ICV protocol, need for subtotal colectomy, and death were described. Associations of patient characteristics with these outcomes were examined with bivariate tests and multivariable logistic models with adjustment for age, hypoalbuminemia, acidosis, and nursing-home status. Thirty-three of 47 patients (70%) with severe C. difficile colitis responded to adjunct ICV with complete resolution without surgery. Incomplete responders who had surgery were more likely to survive than those patients who did not undergo subtotal colectomy (p<0.01). Seven of nine patients who underwent surgery survived >90 d, and overall, 37 of 47 patients (79%) survived after ICV therapy. Nursing-home residence, acidosis, and hypoalbuminemia were significantly associated with the non-resolution of colitis in bivariate analyses (all p<0.01), whereas nursing-home residence and hypoalbuminemia showed non-significant trends toward association with death (p=0.07 and p=0.06, respectively). Multivariate logistic-regression models showed significant associations of acidosis with an incomplete response to ICV (p=0.02), of older age with death (p=0.04), and of hypoalbuminemia with both an incomplete response to ICV and death (both p=0.04). No complications were attributable to ICV. Complete resolution without surgery was achieved in 70% in this series of patients with severe C. difficile colitis who received adjunct ICV therapy. A clinical trial will be needed to determine whether ICV as compared with standard therapy alone can reduce the need for surgery with non-inferior or superior outcomes.

Toxic Megacolon in Clostridium difficile Infection Induced by Topical Silver Sulfadiazine

Background:Clostridium difficile (C. difficile) is a gram positive, spore forming organism usually transmitted by fecal to oral route. The mechanism of mucosal injury is related to its toxin producing activity, capable of inducing severe pseudomembrane formation and mucosal destruction. The use of antibiotics is a well-known risk factor for the development of C. difficile infection. However, the use of topical antibiotics such as silver sulfadiazine (SSD) is rarely associated with the infection; with only one case reported in the English literature. Case Presentation: A 60-year old white male came in for complains of abdominal pain for the past five days associated with abdominal bloating and constipation. PMH was significant for pemphigus vulgaris currently treated with 1% SSD as an adjunct to systemic steroids. Physical examination revealed a distended abdomen, decreased bowel sounds and mild tenderness to palpation. Rectal examination did not reveal any impacted stools, rectal masses and/or visible blood. Initial CBC showed leukocytosis of 17,000/mm3, with a highly significant left shift (28% bands). A subsequent CT of the abdomen revealed a considerable diffuse hypodense thickening of the colon with extensive stranding of the peri-colonic fat suggestive of pancolitis. Stool for C. difficile was subsequently sent, which later came back positive for the toxin. Blood cultures were drawn and he was started on metronidazole, vancomycin oral and vancomycin enema. Over the next three days, he started to develop loose watery stools on several occasions, associated with fever and chills. A repeat CT scan of the abdomen revealed prominent diffuse thickening of the colon with pericolonic inflammatory changes. A surgical evaluation was done, and a subtotal colectomy with ileostomy was performed. Histopathologic evaluation of the specimen revealed extensive pseudomembranous colitis. Clinical Significance: Topical SSD is believed to be absorbed in the system in higher quantities than expected. In a study by Wan et al on burn patients demonstrated a considerable increase of silver content in the blood within six hours after the application of SSD cream, more than 50 fold higher than the normal blood levels. In a similar study by Sano et al on experimental animals also demonstrated an increase in silver absorption on burned, denuded skin. Although topical antibiotics such as silver sulfadiazine has been considered relatively safe for the treatment of different skin infections, its chronic use might play a role in the suppression of the normal gut flora and the subsequent development of C. difficile colitis.

Early Administration of Intracolonic Vancomycin Enema May Improves Survival in Patients with Severe Clostridium difficile Colitis

Early Administration of Intracolonic Vancomycin Enema May Improves Survival in Patients with Severe Clostridium difficile Colitis

Successful Use of Fecal Bacteriotherapy in Severe Crohnʼs Colitis and Refractory Clostridium difficile Infection

Purpose: Fecal bacteriotherapy has been used to treat refractory Clostridium difficile infection, predominantly in an outpatient setting. We describe a patient with severe Crohn's colitis requiring hospitalization in whom fecal bacteriotherapy was successfully used to treat her refractory Clostridium difficile infection. Case: A 33-year-old female with history of Crohn's colitis on azithioprine and adalimumab was admitted with severe abdominal pain, hematochezia, and fever. One month prior to admission, the patient reported frequent bowel movements, abdominal pain and hematochezia. A Clostridium difficile PCR test was positive. Despite two courses of oral vancomycin, her symptoms persisted along with worsening fever, and the patient was subsequently hospitalized. Intravenous metronidazole and vancomycin enemas were started; oral vancomycin was continued. A flexible sigmoidoscopy revealed extensive pseudomembranes. Colonic biopsies revealed severe chronic active colitis but no evidence of cytomegalovirus infection. One dose of IVIG (400 mg/kg) was given on Hospital Day (HD) 3 without clinical improvement. The patient elected to proceed with fecal bacteriotherapy as a potential salvage therapy prior to colectomy. Her husband was screened for HIV and Hepatitis A, B, and C, and his stool was screened for Clostridium difficile, enteric stool pathogens, and ova and parasites. Seventyfive grams of donor stool was emulsified with 200mL normal saline and administered to the patient through a nasogastric tube on HD 10. Over the next several days, the patient's bowel movements became less frequent, and her abdominal pain improved. Two days after stool transfer, a repeat Clostridium difficile PCR test was negative. Over the next week, the patient was started on methylprednisolone and infliximab. The patient's abdominal pain markedly improved, and her hematochezia resolved. The patient was discharged home on HD 23. Discussion: Fecal bacteriotherapy is thought to work by re-establishing essential anerobes and restoring imbalances in stool composition and metabolism. There is a paucity of data in the use of fecal bacteriotherapy in patients with refractory Clostridium difficile infection in the setting of severe Crohn's colitis. In our patient, fecal bacteriotherapy appears to have resolved the Clostridium difficile infection without consequences. After resolving her Clostridium difficile infection, we could then address the patient's underlying Crohn's disease with immunosuppressive therapy. This case suggests a potential role of fecal bacteriotherapy in treating patients with Clostridium difficile infection refractory to traditional therapies who have concomitant severe inflammatory bowel disease.

Turmeric Enema: A Novel Therapy for C. difficile Colitis (CDAD): A Randomized, Double Blinded, Placebo Controlled Prospective Clinical Trial

Purpose: CDAD is a growing clinical challenge in the U.S. Emerging drug resistance is the primary cause of treatment failure causing recurrence. Oral Vancomycin and Metronidazole are the approved therapies. “Turmeric” has been used over centuries in Eastern culture and medicine. It is an antioxidant, anti-ulcerogenic, anti-inflammatory and antimicrobial agent. Turmeric enema has been used in Ulcerative colitis. This clinical trial evaluates the role of turmeric enema in moderate to severe community acquired CDAD. Methods: Thirty-six patients(n=36); mean age of 53 years with moderate to severe CDAD were randomized into three groups: Group A-Placebo(n=11), Group B-Vancomycin enema (n=12) -250mg BD, and Group C-Turmeric enema (n=13), 1gm twice daily for 10 days. All patients received oral metronidazole 500mg thrice daily for 14 days. ATLAS score for clinical severity, stool for C. difficile toxin A/B were measured initially and at the end of therapy. Flexible sigmoidoscopy was performed, pre- and post-therapy after 21 days. Multivariate analysis was obtained among all the groups with clinical score, endoscopic appearance and cost. Results: All patients tolerated the enemas well except Group C with complaints of staining of fomites. 7/11 (66%) in group A compare to 10/12 (83%) in group B, and 10/13 (76%) in group C eradicated the infection. Groups B and C had reduced ATLAS score and endoscopic score of 60% compared to Group A's 38%. The recurrence rate was lower in both Group B-1/10 (10%) and Group C-1/11 (9%) over placebo-2/7 (29%). Post-treatment endoscopic appearance of luminal ulcers with Vancomycin (p=0.037) and Turmeric (p=0.031) compared with the Placebo had a significant difference. Post treatment mucosal bleeding was statistically significant in Turmeric (p =0.001) to vanco (p=0.027). Conclusion: This study demonstrates no significant difference between Turmeric and Vancomycin enema in moderate to severe CDAD. Patient tolerated both enemas with significant cost benefit in turmeric over Vancomycin. A larger control trial is necessary to validate the efficacy.