Clostridium Difficile Polymerase Chain Reaction Research Articles

Pseudomembranous colitis with negative Clostridium difficile PCR presenting with massive ascites: a case report and literature review

Pseudomembranous colitis (PMC) is characterized by the presence of an inflammatory pseudomembrane overlying the colonic mucosa, and is primarily caused by Clostridium difficile infection (CDI). PMC is often associated with the use of broad-spectrum antibiotics. Common symptoms include watery diarrhea, mucus in stool, abdominal cramps, and fever. We report a case of a 52-year-old female presenting with new abdominal distention, frequent bloody, mucoid, jelly-like diarrhea, and abdominal pain. Peritoneal fluid analysis showed neutrocytic ascites with low serum-ascites albumin gradient (SAAG). A diagnosis of pseudomembranous colitis was confirmed by flexible sigmoidoscopy. However, polymerase chain reaction (PCR) test for Clostridium difficile was negative. The patient was treated with metronidazole (500 mg IV q8h) and vancomycin (250 mg PO QID). Her symptoms resolved after several days of treatment with no ascites found by ultrasound. Neutrocytic ascites can be a complication of PMC. Physicians should also be aware that empirical treatment of Clostridium difficile may cause false negative diagnostic test result.

Isolated Colonic Post-Transplantation Lymphoproliferative Disease

A 61-year-old woman with a diagnosis of left-sided ulcerative colitis presented with recurrence of watery nonbloody diarrhea. She was status post liver transplant 2 years prior for primary sclerosing cholangitis, currently on tacrolimus and mesalamine. Following a negative Clostridium difficile polymerase chain reaction, colonoscopy demonstrated Mayo 1 appearance throughout the colon, with an area of friable and hemorrhagic mucosa in the cecum (Figure A). Random colon biopsies showed mild chronic active colitis, but specific biopsies of the cecal patch identified a monomorphous infiltrate of atypical lymphocytes (Figure B).

Comparison of Multiplex Gastrointestinal Pathogen Panel and Conventional Stool Testing for Evaluation of Patients With HIV Infection.

BackgroundGastrointestinal pathogen panels (GPPs) are increasingly used to identify stool pathogens, but their impact in people with HIV (PWH) is unknown. We performed a retrospective cohort study comparing GPP and conventional stool evaluation in PWH.MethodsWe included all PWH who underwent GPP (Biofire Diagnostics; implemented September 15, 2015) or conventional testing, including stool culture, Clostridium difficile polymerase chain reaction testing, fluorescent smears for Cryptosporidium or Giardia, and ova and parasite exams (O&P) from 2013 to 2017. A total of 1941 specimens were tested, with 169 positive specimens detected in 144 patients. We compared result turnaround time, pathogen co-infection, antibiotic treatment, and treatment outcomes between positive specimens detected by conventional testing vs GPP.ResultsOverall, 124 patient samples tested positive by GPP, compared with 45 patient specimens by conventional testing. The GPP group demonstrated a higher co-infection rate (48.4% vs 13.3%; P < .001) and quicker turnaround time (23.4 vs 71.4 hours; P < .001). The GPP identified 29 potential viral infections that were undetectable by conventional stool tests. Unnecessary anti-infective therapy was avoided in 9 of 11 exclusively viral infections. Exclusively nonpathogenic parasites (n = 13) were detected by conventional stool tests, the majority of which were treated with metronidazole. There were no significant differences in clinical outcomes between groups.ConclusionsIn PWH, GPP implementation improved antibiotic stewardship through shorter turnaround times and detection of enteric viral pathogens.

Clinical Impact of Clostridium difficile PCR Cycle Threshold-Predicted Toxin Reporting in Pediatric Patients.

Reliance on tests that detect only the presence of toxigenic Clostridium difficile can result in overdiagnosis and overtreatment of C difficile infection (CDI). The C difficile polymerase chain reaction (PCR) cycle threshold (CT) can sensitively predict the presence of free C difficile toxins; however, the clinical application for this testing strategy remains unexplored. We evaluated the impact of dual PCR and toxin result reporting, as predicted by the CT, on CDI management and outcomes in children. Before the intervention, results for C difficile testing at Lucile Packard Children's Hospital Stanford were reported as PCR positive (PCR+) or negative (PCR-) according to the GeneXpert C diff Epi tcdB PCR assay (Cepheid, Sunnyvale, California). Beginning October 5, 2016, the presence of free toxins, as predicted by the CT, was reported also. The CDI treatment rates 1 year before and 18 months after implementation of toxin reporting were compared. Demographic and treatment-related data were collected, and patient outcomes were followed up 8 weeks later. CDI treatment decreased 22% after the intervention (96% [preintervention] vs 74% [postintervention]; P < .001). During the postintervention period, there were 152 PCR+C difficile results, and 94 (62%) of them were toxin positive (toxin+) according to the CT. Of the 58 PCR+/toxin-negative (toxin-) results, 38 (66%) did not result in CDI treatment. Seven (18%) of the untreated PCR+/toxin- patients underwent repeat testing within 8 weeks, and 5 (13%) of them were subsequently PCR+/toxin+ and treated. No CDI-related complications were identified. Addition of the CT-predicted C difficile toxin result to PCR reporting reduces the proportion of PCR+ children treated for CDI.

Microscopic Colitis: A Rare Cause of Pseudomembranes

A 51-year-old woman with psoriatic arthritis on adalimumab presented with 2 months of diarrhea with 3 to 7 loose stools per day but no other symptoms. Her abdominal examination was benign and her complete blood count was normal. Stool culture, ova and parasites, Clostridium difficile polymerase chain reaction, and fecal leukocytes were negative. A colonoscopy showed pseudomembranes scattered throughout the colon (Figure A) and a normal terminal ileum. Colonic biopsy specimens (Figure B) showed increased lamina propria inflammatory infiltrate, surface epithelial damage, and irregular subepithelial collagen band deposition (Figure B, inset, trichome/Masson stain), with pseudomembrane formation consistent with pseudomembranous collagenous colitis (PCC). Pseudomembranes typically are secondary to ischemia or infectious agents but also can be seen in PCC, a rare variant of microscopic colitis. There have been approximately 20 cases of PCC reported in the literature to date and prior cases have been treated successfully with budesonide. Our patient was treated empirically with oral metronidazole without improvement. She then was given oral budesonide 9 mg/d and showed significant improvement within 3 days and full resolution of symptoms at 1 month. This case highlights the importance of keeping a broad differential diagnosis for pseudomembranes and provides further evidence that PCC responds well to budesonide treatment.

Prevalence of Clostridium Difficile Infection in Patients After Radical Cystectomy and Neoadjuvant Chemotherapy.

Background and Objectives:Clostridium Difficile is the most common cause of nosocomial infectious diarrhea. This study evaluates the prevalence and predictors of Clostridium Difficile infections in patients undergoing radical cystectomy with or without neoadjuvant chemotherapy.Methods:Retrospective chart review was performed of all patients undergoing cystectomy and urinary diversion at a single institution from 2011–2017. Infection was documented in all cases with testing for Clostridium Difficile polymerase chain reaction toxin B. Patient and disease related factors were compared for those who received neoadjuvant chemotherapy vs. those who did not in order to identify potential risk factors associated with C. Difficile infections. Chi squared test and logistic regression analysis were used to determine statistical significance.Results:Of 350 patients who underwent cystectomy, 41 (11.7%) developed Clostridium Difficile in the 30 day post-operative period. The prevalence of C. Difficile infection was higher amongst the patients undergoing cystectomy compared to the non-cystectomy admissions at our hospital (11.7 vs. 2.9%). Incidence was not significantly different among those who underwent cystectomy for bladder cancer versus those who underwent the procedure for other reasons. Median time to diagnosis was 6 days (range 3–28 days). The prevalence of C. Diff infections was not significantly different among those who received neoadjuvant chemotherapy vs. those who did not (11% vs. 10.4% p = 0.72). A significant association between C. Difficile infection was not seen with proton pump inhibitor use (p = 0.48), patient BMI (p = 0.67), chemotherapeutic regimen (p = 0.94), individual surgeon (p = 0.54), type of urinary diversion (0.41), or peri-operative antibiotic redosing (p = 0.26).Conclusions:Clostridium Difficile infection has a higher prevalence in patients undergoing cystectomy. No significant association between prevalence and exposure to neoadjuvant chemotherapy was seen.

Optimal strategies for the diagnosis of community-onset diarrhea in solid organ transplant recipients: Less is more.

Diarrhea, a common complication after solid organ transplant (SOT), is associated with allograft failure and death. No evidence-based guidelines exist for the evaluation of diarrhea in SOT recipients. We performed a cost analysis to derive a testing algorithm for the diagnosis of community-onset diarrhea that minimizes costs without compromising diagnostic yields. A cost analysis was performed on a retrospective cohort of 422 SOT admissions for community-onset diarrhea over an 18-month period. A stepwise testing model was applied on a population level to assess test costs relative to diagnostic yields. Over an 18-month period, 1564 diagnostic tests were performed and 127 (8.1%) returned positive. Diagnostic testing accounted for $95 625 of hospital costs. The tests with the lowest cost per decrease in the false-omission rate (FOR) were stool Clostridium difficile polymerase chain reaction (PCR) ($156), serum cytomegalovirus quantitative PCR ($1529), stool norovirus (NV) PCR ($4673), and stool culture ($6804). A time-to-event analysis found no significant difference in the length of hospital stay between patients with and without NV testing (P=.520). A stepwise testing strategy can reduce costs without compromising diagnostic yields. In the first-stage testing, we recommend assessment for C.difficile, cytomegalovirus, and food-borne bacterial pathogens. For persistent diarrheal episodes, second-stage evaluation should include stool NV PCR, Giardia/Cryptosporidium enzyme immunoassay, stool ova and parasite, reductions in immunosuppressive therapy, and possibly endoscopy. Although NV testing had a relatively low cost per FOR, we recommend NV testing during second-stage evaluation, as an NV diagnosis may not lead to changes in clinical management or further reductions in length of hospital stay.

Clinical and Microbiological Characteristics of Clostridium difficile Infection Among Hospitalized Children in the Netherlands.

Little is known about pediatric Clostridium difficile infection (CDI) epidemiology. We describe the clinical and microbiological characteristics of CDI among hospitalized children in the Netherlands. Between May 2009 and May 2015, 26 hospitals registered characteristics of pediatric (aged 2-18 years) and adult (aged 18 years) CDI in a national sentinel surveillance study. Routine polymerase chain reaction (PCR) ribotyping and multiple-locus variable-number tandem-repeat analysis (MLVA) of selected strains was performed. Pediatric and adult results were compared using proportion and 95% confidence interval (CI). Time trend of pediatric CDI was evaluated using a mixed-effect Poisson model. Pediatric CDIs were reported in 17 of the 26 participating hospitals (n = 135; 3% of all CDIs); the monthly number was constant over time. The median age of pediatric cases was 10 years (interquartile range, 4.7-14.5 years). Fifty-five percent of the children had community onset and 31% had severe CDI. Compared with adults (n = 4,556), complication and mortality rates were lower. Clostridium difficile PCR ribotype 265 (toxin A negative, B positive) was most prevalent in children (15%; 95% CI, 8.8%-24.0%) but rarely found in adults (1%; 95% CI, 0.9%-1.6%). This strain was rarely found in other countries, except for Belgium. MLVA showed genetic relatedness between three-fourths of pediatric and adult ribotype 265 strains, without a clear epidemiological link. Pediatric CDI in hospitals has remained stable over the last 6 years and resulted in fewer complications than for adult CDI. Further studies are needed to elucidate the source and epidemiology of PCR ribotype 265, primarily found in children.

A Case of Narcotic Bowel Syndrome

Narcotic bowel syndrome (NBS) is becoming increasingly recognized although it is a challenging and under-diagnosed condition. It is characterized chronic or recurrent and unresolving abdominal pain associated with escalating doses of narcotic pain medications. A 64-year-old male patient with a history of unremitting chronic abdominal pain despite extensive negative organic gastrointestinal workup, on high extremely dose opioids presented to the hospital with continued abdominal pain and new onset explosive diarrhea for seven days. On admission, he was normotensive and afebrile. Abdominal examination revealed a soft, diffusely tender to palpation, distended abdomen with normal bowel sounds. Laboratory workup showed normocytic normochromic anemia, no leukocytosis, and liver and kidney function within normal limits. KUB showed dilated loops of bowel. CT abdomen revealed distention of the entire colon, measuring up to 9.3cm at the level of the distal transverse colon without small bowel or colonic obstruction and no evidence of bowel ischemia (Figure A). Patient had positive Clostridium difficile polymerase chain reaction (PCR) for which he was treated. Repeat Clostridium difficile PCR was negative. Flexible sigmoidoscopy revealed dilated colon without pseudomembranes (Figure B). Despite treatment of CDI, patient continued to endorse abdominal pain and distention during hospitalization and on follow up. The diagnostic criteria for NBS is chronic or intermittent abdominal pain, sometimes severe, as the predominant symptoms with at least three of the following; pain worsens or dose not resolved with continued or escalating doses of narcotics; the episodes of pain have a progression of frequency, duration and intensity; when the narcotic dose wanes, a markedly intense pain is felt which improves with reinstitution of narcotic; other causes of gastrointestinal etiology for the pain have been ruled out or cannot be explained otherwise. The patient population that develops NBS is often originally prescribed opioids for intra-abdominal or extra-abdominal etiology. Over time, abdominal pain develops or worsens. The best treatment for NBS is to de-escalate opioid doses and frequency. The persistence of chronic, intermittent, crampy abdominal pain especially when symptoms worsen with effects of narcotics wear off should prompt physicians to keep narcotic bowel syndrome very high on the differential even when faced with concomitant infections.Figure 1Figure 2

An exploratory study to evaluate Clostridium difficile polymerase chain reaction ribotypes and infection outcomes.

BackgroundClostridium difficile infection ranges from mild to severe prolonged diarrhea with systemic symptoms. Previous studies have assessed the correlation of some disease severity parameters to C. difficile ribotypes. However, certain clinical parameters of interest have not yet been evaluated.AimWe conducted an exploratory study to evaluate the correlation of C. difficile ribotypes to parameters not assessed previously, notably days to diarrhea resolution (in terms of days to formed stools and days to less than three stools per day), length of hospital stay, 30-day recurrence rates, and 30-day readmission rates. Additional severity parameters evaluated include leukocytosis, serum creatinine, fever, and nausea/vomiting.MethodsPolymerase chain reaction ribotyping was performed on C. difficile isolates from baseline stool samples of 29 patients. A retrospective chart review was conducted to assess the parameters of interest.ResultsThe most common ribotypes were 027 (38%), 014/020 (21%), and 106/174 (21%). Numerically, 027 ribotype patients required more days to less than three stools per day versus 014/020 and 106/174 ribotype patients (P=0.2). The three ribotypes were similar regarding time to formed stools, duration of hospitalization, and 30-day readmission rate (P=0.2, 0.6, and 0.8, respectively). Recurrence within 30 days occurred in two patients with 027 and two patients with 014/020 (P=0.6). Leukocytosis and fever were more prominent with 027 than with 014/020 and 106/174 (P=0.04 for both parameters), although the degree of nausea/vomiting did not differ between the three groups (P=0.3). A serum creatinine level ≥1.5 times the premorbid level was seen in only three patients, each infected with a different ribotype.ConclusionAlthough these data provide a baseline assessment of outcomes to aid in the design of future studies, the diversity of C. difficile ribotypes within the population must be considered, and additional work with other ribotypes may further explain the association with these outcomes.

Impact of a Healthcare Provider Educational Intervention on Frequency of Clostridium difficile Polymerase Chain Reaction Testing in Children: A Segmented Regression Analysis.

Although Clostridium difficile infections (CDIs) are increasingly diagnosed in children, many children diagnosed with CDI lack classic risk factors. Frequent use of highly sensitive tcdB polymerase chain reaction (PCR) testing in low-risk patients leads to CDI misdiagnosis and unnecessary CDI antibiotic use in children with C difficile carriage. For this quasi-experimental study, we developed and implemented an educational intervention (EI) to inform healthcare providers (HCPs) about tcdB PCR test limitations. We provided HCP didactic education and built an electronic notification into the tcdB PCR test order that describes scenarios in which carriage is more likely than CDI. Segmented regression analysis assessed changes in level (ie, overall rates) and trend of C difficile testing rate ([TR] number of tests performed per 1000 patient encounters) and test positivity rate ([PR] number of positive tests per 1000 patient encounters) between the pre- (August 2009-August 2013) and postintervention (February 2014-July 2015) periods. Hospital-wide, absolute TR reduction was 0.71 (P[level] = .0067; P[trend] = .0042) and absolute PR reduction was 0.14 (P[level] = .22; P[trend] = .018). In the outpatient setting, absolute TR reduction was 0.30 (P[level] = .0015; P[trend] < .001) and absolute PR reduction was 0.09 (P[level] = .0069; P[trend] = .046). The incidence density of healthcare facility-associated CDI did not significantly change after the EI. The EI was associated with avoidance of 574 tests and 113 positive tests (and subsequent antibiotic courses) during the postintervention period, which saved approximately $250 000 in patient charges related to CDI testing and treatment. Healthcare provider education can cost-effectively reduce the frequency of C difficile testing and CDI misdiagnosis by improving test utilization among low-risk children.

MP06-18 PREVALENCE OF CLOSTRIDIUM DIFFICILE INFECTION IN PATIENTS AFTER RADICAL CYSTECTOMY AND NEOADJUVANT CHEMOTHERAPY

You have accessJournal of UrologyBladder Cancer: Epidemiology & Evaluation II1 Apr 2016MP06-18 PREVALENCE OF CLOSTRIDIUM DIFFICILE INFECTION IN PATIENTS AFTER RADICAL CYSTECTOMY AND NEOADJUVANT CHEMOTHERAPY Katherine Cotter, Owen Aftreth, John Schomburg, Yunhua Fan, and Badrinath Konety Katherine CotterKatherine Cotter More articles by this author , Owen AftrethOwen Aftreth More articles by this author , John SchomburgJohn Schomburg More articles by this author , Yunhua FanYunhua Fan More articles by this author , and Badrinath KonetyBadrinath Konety More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2179AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Clostridium Difficile is the most common cause of nosocomial infectious diarrhea, with a recent prevalence rate of 8.8% described in the post-radical cystectomy population. This study evaluates the prevalence of Clostridium Difficile infections in patients undergoing radical cystectomy who have previously received neoadjuvant chemotherapy. METHODS Retrospective chart review was performed of all patients undergoing radical cystectomy at a single institution from 2011-2015. Infection was diagnosed with the Clostridium Difficile polymerase chain reaction toxin B in the post-operative period. A chi-squared test was used to compare patients who received neoadjuvant chemotherapy with those who only underwent radical cystectomy in order to identify potential risk factors associated with C. Difficile infections. All patients received a standard dose of intravenous antibiotic within 30 minutes of incision. If administered, antibiotic redosing within the 24 hour peri-operative period was documented. RESULTS Of the 133 patients who underwent radical cystectomy, 14 developed Clostridium Difficile in the post-operative period. Median time to diagnosis was 6 days (range 3-28 days) in all patients, with 5.5 days in the post-chemotherapy group and 7.0 in the cystectomy only group. A total of 43 patients received neoadjuvant chemotherapy, and 6/43 (14%) developed C. Difficile infection. A total of 90 patients received neoadjuvant chemotherapy, and 8/90 (9%) developed C. Difficile infection (p=NS). This yielded an overall rate of Clostridium Difficile infection of 105 per 1000 and specifically 139 per 1000 among those undergoing neoadjuvant chemotherapy and 89 per 1000 in those undergoing only radical cystectomy. The rate of infection in patients without NAC was equivalent to the prevalence recorded in the literature (9%), but the prevalence was higher (14%) in patients receiving NAC. Median length of hospital stay was 16 in the post-chemotherapy group and 9 in the cystectomy only group (p=0.08). An association between C. Difficile infection prevalence was not seen with proton pump inhibitor use (p=1.0) or peri-operative antibiotic redosing (p=0.26). CONCLUSIONS The incidence of Clostridium Difficile infection is quite prevalent in patients undergoing radical cystectomy for bladder cancer. The rate of post-operative infection may be higher in those patients who receive neoadjuvant chemotherapy. Judicious use of antibiotics, rapid testing, and prompt therapy can help reduce the morbidity of this infection. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e74 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Katherine Cotter More articles by this author Owen Aftreth More articles by this author John Schomburg More articles by this author Yunhua Fan More articles by this author Badrinath Konety More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Characteristics of Clostridium difficile infection in patients with discordant diagnostic test results.

Clinical features of Clostridium difficile infection (CDI) cases diagnosed by detection of polymerase chain reaction (PCR), with negative toxin enzyme immunoassay results (EIA) have not been fully elucidated. The purpose of this study was to determine the magnitude of CDI patients who had negative EIA toxin determinations but positive PCR tests, and their differences in clinical presentation. We performed a retrospective study comparing the clinical features of CDI cases detected by EIA (toxins A + B) with cases detected by PCR (toxin negative, PCR positive) over a 16-month period. Only patients with an initial Clostridium difficile infection episode that fulfilled a standardized definition were included. During the study period, 107 episodes of CDI were detected. Seventy-four patients (69%) had positive glutamate dehydrogenase (GDH) antigen and EIA determinations (EIA positive patients). Thirty-three patients (31%) had GDH positive, negative toxin EIA and positive PCR determination (PCR positive patients). PCR positive patients were younger, 57 (27) years (mean [SD]), than EIA positive patients, 71 (16) years, (p < 0.001). Fewer PCR positive patients were receiving proton pump inhibitors (21 patients, 64%) than EIA positive patients (61 patients, 82%, p = 0.034). The clinical presentation was similar in both groups. In the multivariate analysis, lower age was identified as the only independent variable associated with PCR positive patients. One third of Clostridium difficile infection patients present negative toxin EIA and PCR positive tests. Performing PCR determination after the negative EIA test is more relevant in younger patients.

A Healthcare Provider Educational Intervention to Reduce Unnecessary Clostridium difficile Polymerase Chain Reaction Testing in Pediatric Patients: A Segmented Regression Analysis

A Healthcare Provider Educational Intervention to Reduce Unnecessary Clostridium difficile Polymerase Chain Reaction Testing in Pediatric Patients: A Segmented Regression Analysis

Clostridium difficile infection (CDI) severity and outcome among patients infected with the NAP1/BI/027 strain in a non-epidemic setting.

Determine whether the NAP1 strain identified by polymerase chain reaction (PCR)-based stool assay is correlated with CDI severity and clinical outcomes. Medical records of adult patients with positive stool Xpert® Clostridium difficile PCR assay for an initial episode of CDI between January 2012 and January 2013 at a tertiary care hospital in Chicago were reviewed. Two patients diagnosed with CDI caused by a non-NAP1 strain (positive Xpert® C. difficile assay but negative Xpert® C. difficile Epi assay) were included for each patient diagnosed with CDI caused by a NAP1 strain (positive Epi assay). Patient charts were reviewed for markers of severity, risk factors, treatment regimens, and outcomes. Of 494 stool specimens, 90 (18%) that were positive for C. difficile by PCR were positive for NAP1 strain. In total, 37 patients with CDI due to NAP1 were matched with 74 patients with CDI due to non-NAP1 strains. Multivariable model revealed individuals ≥65 years old were 3 times more likely to have NAP1 strain than individuals <65 (P=.02). Residents of a nursing home prior to hospitalization were 10 times more likely to have NAP1 strain than patients residing in their homes (P=.001). More NAP1 cases had a change in treatment from metronidazole to oral vancomycin plus intravenous metronidazole (P=.01). The severity of CDI, incidence of mortality and recurrent CDI were similar between groups. In a nonepidemic setting, NAP1 strains were more common in older patients and individuals admitted from nursing homes. Identification of NAP1 by PCR of stool specimens was associated in a change of therapy but did not predict worse outcomes. Reporting strain results may not be clinically useful in routine settings.

Chronic Diarrhea and Weight Loss

Question: A 61year-old black man with a past medical history of hypertension, hyperlipidemia, and coronary artery disease presented in January 2013 for evaluation of chronic nonbloody diarrhea and weight loss of 60 pounds over the past 2 years. Associated symptoms included abdominal discomfort, loss of appetite, and fatigue. Current medications included amlodipine, budesonide, pravastatin, olmesartan, and aspirin. An extensive evaluation including routine laboratory tests, stool cultures, stool ova þ parasites, stool analysis, Clostridium difficile polymerase chain reaction, celiac panel (immunoglobulin A/TTG), thyroid-stimulating hormone, immunoglobulin, serum protein electrophoresis, plasma peptides (gastrin, calcitonin, vasoactive intestinal peptide, somatostatin), urine 5-hydroxy-indole-acetic acid, and tumor markers (carcinoembryonic antigen, carbohydrate antigen19-9, alfa fetoprotein) were unremarkable. Fecal fat was 19 g over 24 hours. He was started on trial of pancreatic enzymes without clinical benefit. Glucose breath test was negative for small bowel bacterial overgrowth. Further diagnostic testing including computed tomography of the abdomen and small bowel follow through excluded structural disease. He was subsequently diagnosed with lymphocytic colitis as per biopsies done on colonoscopy in October 2012 and was treated with oral budesonide. He noticed slight improvement in diarrhea, but continued to experience loss of weight and decreased appetite. Endoscopic ultrasonography, to rule out chronic pancreatitis, was normal. Esophagogastroduodenoscopy with gastric and duodenal biopsies done in 2012 are shown in Figures A and B, respectively. What is the diagnosis? Look on page 591 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.

Unnecessary repeat Clostridium difficile PCR testing in hospitalized adults with C. difficile-negative diarrhea

The aim of this study was to determine the extent and associated costs of repeat Clostridium difficile stool polymerase chain reaction (PCR) assays in patients with initially negative PCRs. C. difficile stool PCRs were done on adult hospitalized patients with diarrhea. The number/time course of repeat PCRs on initially negative PCR patients was determined. Of 5,027 C. difficile stool PCRs, 814 (16.2 %) were positive and 4,213 (83.8 %) were negative. Ninety-seven of the initially PCR-negative patients had >2 repeat tests 1-59 days after the initial negative stool PCR. Repeat negative PCR testing rarely resulted in a subsequent positive result (0.05 %). The unnecessary costs of 97 repeat PCRs was $32,658.00. Many of these patients were originally given empiric oral anti-C. difficile therapy, in spite of repeatedly negative PCRs.

Ipilimumab Induced Enterocolitis - A Novel Cause of Diarrhea

Purpose: A 64 year-old man presented for evaluation of watery, non-bloody diarrhea. He was having up to ten bowel movements per day with multiple episodes of emesis. He was participating in a clinical trial comparing ipilimumab versus placebo for treatment of hormone refractory metastatic prostate cancer and had just completed his fourth infusion. On examination he was dehydrated, so he was admitted to the hospital for intravenous hydration. Enteric pathogen analysis including Clostridium difficile polymerase chain reaction was negative. The patient underwent a flexible sigmoidoscopy that demonstrated scattered focal erythema and erosions. Random colonic biopsies showed focal active colitis characterized by patchy infiltration of crypts by polymorphonuclear leukocytes. No increase in intraepithelial lymphocytes or granulomas was observed. Cytomegalovirus immunostaining was negative. His diarrhea improved with a five day course of methylprednisolone 125 mg daily and he was discharged home to complete a six week prednisone taper. Follow-up imaging one month later showed marked improvement in metastatic disease burden as well as prostate specific antigen levels. Ipilimumab is a cytotoxic T-lymphocyte-associated antigen 4 antibody that allows immune disinhibition of T cells leading to targeted tumor regression. It was recently approved for treatment of metastatic melanoma and is currently being evaluated for both prostate and lung cancer. Immune-mediated toxicities may represent a marker for treatment efficacy, as in the present case. Immune-mediated toxicity is most prevalent in the gastrointestinal tract with a reported incidence of enterocolitis in up to 21% of patients undergoing treatment. The cumulative dose administered does not appear to predict the risk for developing ipilimumab induced enterocolitis. The clinical hallmark of ipilimumab induced enterocolitis is profound watery diarrhea that may also present with abdominal pain, nausea, vomiting, and/or fever. Diagnosis is confirmed via endoscopic evaluation, which demonstrates colonic erythema, ulceration, and potentially gastritis and/or duodenitis. Histopathological findings include acute colonic neutrophilic and/or lymphocytic infiltrates. Oral corticosteroids can be used for treatment of mild cases (<6 bowel movements per day). Severe cases (>7 bowel movements per day) however, may require hospitalization with administration of high-dose intravenous steroids followed by an oral taper. Refractory cases have been successfully managed by administering one dose of infliximab (5 mg/kg). Timely diagnosis and treatment is critical to avoid unnecessary premature discontinuation of therapy or complications such as colonic perforation.

Rapid detection of the Clostridium difficile ribotype 027 tcdC gene frame shift mutation at position 117 by real-time PCR and melt curve analysis

The emergence of the hypervirulent strain Clostridium difficile PCR ribotype 027 has increased the necessity for rapid C. difficile typing tests for clinical and epidemiological purposes. We developed a rapid real-time polymerase chain reaction (PCR) test for the detection of C. difficile. As the target, we chose the tcdC gene, which encodes for a negative regulator in toxin production. A deletion at position 117 of the tcdC gene, which is associated with severe tcdC truncation, is well conserved in all PCR ribotype 027 isolates. Probe sequences of the real-time PCR test were designed to result in distinct melt profiles for sequence variations at positions 117 to 120 of the tcdC gene. The tcdC gene deletion at position 117 was easily detected with real-time PCR and melt curve analysis in all C. difficile ribotype 027 isolates. In five non-027 strains and 46 hospitalised patient samples, melt curve analysis detected no deletion. PCR results were confirmed by DNA sequencing. The combination of real-time PCR and melt curve analysis is a rapid and accurate method for the detection of C. difficile DNA and simultaneous screening for the tcdC gene deletion at position 117, which is closely related to the C. difficile PCR ribotype 027 strain.

Risk Factors Related to a Hospital-Associated Cluster ofClostridium difficilePCR Ribotype 027 Infections in Germany During 2007

In 2007, Clostridium difficile polymerase chain reaction (PCR) ribotype 027 emerged in Germany. We conducted a hospital-based case-control study to identify specific risk factors for infection with this strain. Logistic regression analysis involving 15 case patients and 31 control patients revealed that exposure to fluoroquinolones (matched odds ratio, 36.2; P < .01) or cephalosporins (matched odds ratio, 19.1; P < .01) was independently related to C. difficile PCR ribotype 027 infection.