Clinical Predictors of Fulminant Colitis in Patients with Clostridium difficile Infection

Background/Aim:

Clostridium difficile infection (CDI) can affect up to 8% of hospitalized patients. Twenty-five percent CDI patients may develop C. difficile associated diarrhea (CDAD) and 1–3% may progress to fulminant C. difficile colitis (FCDC). Once developed, FCDC has higher rates of complications and mortality.

Patients and Methods:

A 10-year retrospective review of FCDC patients who underwent colectomy was performed and compared with randomly selected age- and sex-matched non-fulminant CDAD patients at our institution. FCDC (n=18) and CDAD (n=49) groups were defined clinically, radiologically, and pathologically. Univariate analysis was performed using Chi-square and Student''s t test followed by multivariate logistic regression to compute independent predictors.

Results:

FCDC patients were significantly older (77 ± 13 years), presented with triad of abdominal pain (89%), diarrhea (72%), and distention (39%); 28% had prior CDI and had greater hemodynamic instability. In contrast, CDAD patients were comparatively younger (65 ± 20 years), presented with only 1 or 2 of these 3 symptoms and only 5% had prior CDI. No significant difference was noted between the 2 groups in terms of comorbid conditions, use of antibiotics, or proton pump inhibitor. Leukocytosis was significantly higher in FCDC patients (18.6 ± 15.8/mm³ vs 10.7 ± 5.2/mm³; P=0.04) and further increased until the point of surgery. Use of antiperistaltic medications was higher in FCDC than CDAD group (56% vs 22%; P=0.01).

Conclusions:

Our data suggest several clinical and laboratory features in CDI patients, which may be indicative of FCDC. These include old age (>70 years), prior CDI, clinical triad of increasing abdominal pain, distention and diarrhea, profound leukocytosis (>18,000/mm³), hemodynamic instability, and use of antiperistaltic medications.     

Impact of Clostridium difficile infection on inflammatory bowel disease outcome: A review

Although a considerable number of studies support a substantial increase in incidence, severity, and healthcare costs for Clostridium difficile infection (CDI) in inflammatory bowel disease (IBD), only few evaluate its impact on IBD outcome. Medline and several other electronic databases from January 1993 to October 2013 were searched in order to identify potentially relevant literature. Most of the studies showed that IBD patients with CDI present a greater proportion of worse outcomes than those without CDI. These patients have longer length of hospital stay, higher rates of colectomies, and increased mortality. Patients with ulcerative colitis are more susceptible to CDI and have more severe outcomes than those with Crohn’s disease. However, studies reported variable results in both short- and long-term outcomes. Contrasting results were also found between studies using nationwide data and those reporting from single-center, or between some North-American and European studies. An important limitation of all studies analyzed was their retrospective design. Due to contrasting data often provided by retrospective studies, further prospective multi-center studies are necessary to evaluate CDI impact on IBD outcome. Until then, a rapid diagnosis and adequate therapy of infection are of paramount importance to improve IBD patients’ outcome. The aim of this article is to provide up to date information regarding CDI impact on outcome in IBD patients.     

INCIDENCE OF DIARRHEA BY Clostridium difficile IN HEMATOLOGIC PATIENTS AND HEMATOPOIETIC STEM CELL TRANSPLANTATION PATIENTS: RISK FACTORS FOR SEVERE FORMS AND DEATH

We describe the rate of incidence of Clostridium difficile-associated diarrhea (CDAD) in hematologic and patients undergone stem cell transplant (HSCT) at HC-FMUSP, from January 2007 to June 2011, using two denominators 1,000 patient and 1,000 days of neutropenia and the risk factors associated with the severe form of the disease and death. The ELISA method (Ridascreen-Biopharm, Germany) for the detections of toxins A/B was used to identify C. difficile. A multivariate analysis was performed to evaluate potential factors associated with severe CDAD and death within 14 days after the diagnosis of CDAD, using multiple logistic regression. Sixty-six episodes were identified in 64 patients among 439 patients with diarrhea during the study period. CDA rate of incidence varied from 0.78 to 5.45 per 1,000 days of neutropenia and from 0.65 to 5.45 per 1,000 patient-days. The most common underlying disease was acute myeloid leukemia 30/64 (44%), 32/64 (46%) patients were neutropenic, 31/64 (45%) undergone allogeneic HSCT, 61/64 (88%) had previously used antibiotics and 9/64 (13%) have severe CDAD. Most of the patients (89%) received treatment with oral metronidazole and 19/64 (26%) died. The independent risk factors associated with death were the severe form of CDAD, and use of linezolid.     

The Simple Predictors of Pseudomembranous Colitis in Patients with Hospital-Acquired Diarrhea: A Prospective Observational Study

Background/Aims

As the incidence rate of and mortality from pseudomembranous colitis (PMC) are increasing worldwide, it is important to study the simple predictive risk factors for PMC among patients with hospital-acquired diarrhea (HAD). This study focused on identifying the clinical risk factors that can easily predict PMC.

Methods

The presumed HAD patients were prospectively recruited at the Hallym University Kangdong Sacred Heart Hospital.

Results

Age of 70 and older (adjusted odds ratio [OR], 1.76; 95% confidence interval [CI], 1.12 to 0.75), use of proton pump inhibitors (adjusted OR, 4.07; 95% CI, 2.512 to 6.57), use of cephalosporins (adjusted OR, 2.99; 95% CI, 1.82 to 4.94), and underlying cancer (adjusted OR, 1.72; 95% CI, 1.04 to 2.82) were independent risk factors for PMC in the multivariate logistic regression analysis. The prevalence of PMC was very low in the patients with HAD who exhibited no risk factors.

Conclusions

The risk factors for PMC in patients with HAD included cephalosporin use, proton pump inhibitor use, old age, and cancer. Considering the strongly negative predictive values of these risk factors, endoscopic evaluation can be delayed in patients with HAD without risk of developing PMC.     

Ulcerative colitis worsened after Clostridium difficile infection:Efficacy of infliximab

The incidence of Clostridium difficile(C.difficile)infection(CDI)is 1.8%-5.7%in admitted patients with ulcerative colitis(UC).CDI can worsen UC and increase the risk for colectomy or even death,thus necessitating therapy escalation,such as increasing the corticoid therapy or starting a biologic treatment.Several reported cases with infliximab therapy have provided favorable outcomes in UC patients with CDI,suggesting that infliximab treatment may be protective;however,the optimal infliximab treatment regimen for UC patients with CDI remains to be established.Here,we report a case of worsening UC in the presence of recurrent CDI.The patient had received prior ciprofloxacin and immunosuppressive therapy during a prolonged hospital stay.The deterioration in the patient’s condition likely resulted from the ability of C.difficile to promote relapsing of UC by activating the immune response.Ultimately,the patient was treated with a high dose of infliximab after a low trough level of infliximab at week 8was identified,yielding better clinical results.Infliximab was found to be safe after repetitive episodes of CDI.The trough level of infliximab was therefore a useful indicator to guide therapy and correlated well with the patient’s outcome.     

A Rare Case of Ulcerative Colitis with Severe Pneumocystis jirovecii Pneumonia and Cytomegalovirus Colitis: A Case Report and Literature Review

Pneumocystis jirovecii pneumonia (PJP) and cytomegalovirus (CMV) colitis are opportunistic infections that occur during immunosuppressive treatments for ulcerative colitis (UC). The prognosis of PJP and CMV colitis is very poor. We herein report a rare case of a 74-year-old UC patient with PJP and CMV colitis that was successfully treated with intensive therapy. PJP progresses rapidly, so the timing and choice of treatment are critical. Furthermore, a literature review of similar cases suggested that prophylactic therapy for opportunistic infections might be important, especially in the elderly. This case will serve as a reference for successful treatment in future cases.     

The interplay between microbiome dynamics and pathogen dynamics in a murine model of Clostridium difficile Infection

Clostridium difficile infection (CDI) arises in the setting of antibiotic administration where disruption of the normal indigenous gut microbiota leads to susceptibility to C. difficile colonization and colitis. Using a murine model of CDI, we demonstrate that changes in the community structure of the indigenous gut microbiota are associated with the loss of colonization resistance against C. difficile. Several antibiotic regimens were tested in combination for the ability to overcome colonization resistance, including a five antibiotic cocktail consisting of kanamycin, gentamicin, colistin, metronidazole, and vancomycin administered in drinking water for three days, a single intraperitoneal dose of clindamycin or 10 days of cefoperazone in drinking water. Following antibiotic treatment animals were challenged with 105 colony forming units of C. difficile strain VPI 10463 via oral gavage. Animals that received the antibiotic cocktail and clindamycin prior to C. difficile challenge followed one of two clinical courses, either becoming clinically ill and moribund within 2-4 days post challenge, or remaining clinically well. Animals that became clinically ill developed histologically severe colitis. These histopathologic findings were significantly less severe in animals that remained clinically well. Analysis of 16S rRNA gene sequences retrieved from gut tissue at necropsy demonstrated that Proteobacteria dominated the gut microbiota in clinically ill animals. In contrast, the gut microbial community of clinically well animals more closely resembled untreated animals, which were dominated by members of the Firmicutes. All animals that received cefoperazone treatment prior to C. difficile challenge were clinically ill and moribund by 2-5 days post challenge in a dose dependent manner. The gut communities in these animals were dominated by C.difficile suggesting that cefoperazone treatment resulted in a greater loss in colonization resistance. Thus, the severity of colitis that arises in this system reflects the interplay between the expansion of C. difficile in the gut community and the ecologic dynamics of the indigenous microbial community as it recovers from antibiotic perturbation. We demonstrate that altering the balance of these two opposing processes alters clinical outcome and thus may lead to novel preventative and therapeutic approaches for CDI.     

Recurrent Clostridium difficile infections: The importance of the intestinal microbiota

Clostridium difficile infections (CDI) are a leading cause of antibiotic-associated and nosocomial diarrhea. Despite effective antibiotic treatments, recurrent infections are common. With the recent emergence of hypervirulent isolates of C. difficile, CDI is a growing epidemic with higher rates of recurrence, increasing severity and mortality. Fecal microbiota transplantation (FMT) is an alternative treatment for recurrent CDI. A better understanding of intestinal microbiota and its role in CDI has opened the door to this promising therapeutic approach. FMT is thought to resolve dysbiosis by restoring gut microbiota diversity thereby breaking the cycle of recurrent CDI. Since the first reported use of FMT for recurrent CDI in 1958, systematic reviews of case series and case report have shown its effectiveness with high resolution rates compared to standard antibiotic treatment. This article focuses on current guidelines for CDI treatment, the role of intestinal microbiota in CDI recurrence and current evidence about FMT efficacy, adverse effects and acceptability.     

A Study on Atypical Endoscopic Findings of Ulcerative Colitis: Longitudinal Ulcers,Mucosal Bridges and Red Spots

Abstract: One hundred and twenty-one ulcerative colitis patients diagnosed during the period of 1984 to 1988 were examined endoscopically on repeated occasions. Forty-six patients had total colitis, 56 had left-sided colitis, 15 had proctitis, and 4 were postoperative patients. When classified according to their macroscopic findings, 28 of the patients had the polyposis type of this disease, 88 had the atrophic type, and 5 had the mixed type. Longitudinal ulcers were found in 9 patients, occuring usually in the sigmoid colon. There was no pathological evidence of ischemic changes in these 9 patients. Mucosal bridges were found in 13 of the patients with total colitis, occurring somewhere from the cecum to the rectum. The mucosal bridges tended to be present during the mildly active stage of the disease. Red spots, which sometimes looked like vascular spiders, were found in 10 patients. The spots tended to appear before the disease went into the inactive stage. Histological observation showed regenerating vessels, sometimes with intramucosal bleeding; therefore the spots seemed to be intractable changes.     

Epithelial Proliferation and ras p21 Oncoprotein Expression in Rectal Mucosa of Patients with Ulcerative Colitis

In ulcerative colitis (UC), epithelial proliferation plays a role in crypt repair and neoplastic evolution. Proliferative status is predominantly connoted in active disease, but not defined in remission. Histologically, remission is characterized by normalization of the picture or development of atrophy. Mutation of the ras oncogene is involved in intestinal carcinogenesis. Aim of this work was to assess the proliferative pattern of rectal epithelium in UC during disease activity and in remission and correlate it with ras oncoprotein p21. The study was performed retrospectively in rectal biopsies from four groups each of 10 patients: active ulcerative colitis (AUC), remission with a normal histology (RUC), remission with rectal atrophy (ARUC), and irritable bowel syndrome (C, control group). In all, immunohistostain was employed to evaluate the proliferation cell nuclear antigen labeling index (PCNA LI) and ras p21. Statistical analysis was performed by ANOVA and Student-Neumann-Keuls tests. %PCNA LI was significantly higher in AUC and ARUC than in RUC and C. Positive cells were predominant in the lower zone of crypts in RUC and C, while a significant expression of PCNA was also observed in the upper areas in AUC and ARUC. Oncoprotein p21 was expressed on the apical surface of the epithelium in 3/10 AUC patients, in all 10 ARUC patients and in none of RUC and C. %The persistently increased epithelial proliferation associated with ras p21 expression in ARUC may be due to the action of an abnormal, mutated ras gene that could play a role in UC-related tumorigenesis.     

Treatment of Ulcerative Colitis with High Doses of Oral Prednisolone : The Rate of Remission,the Need for Surgery,and the Effect of Prolonging the Treatment

Kjeldsen J. Treatment of ulcerative colitis with high doses of oral prednisolone. The rate of remission, the need for surgery, and the effect of prolonging the treatment. Scand J Gastroenterol 1993;28:821-826.

Treatment of acute attacks of ulcerative colitis in 89 patients with doses of prednisolone above or equal to 40 mg resulted in an overall remission in 67%. Remission rate and colectomy rate were 47% and 42%, respectively, when the disease was severe, 80% and 13% when moderate, and 84% and 3% when mild. The need for surgery was 28% in pancolitis, 11% in left-sided colitis, and 5% in proctitis. After subsequent treatment episodes colectomy was performed in 35% of patients with pancolitis, in 37% with left-sided colitis, and in 5% with proctitis. The median total duration of therapy in patients who went into clinical remission was 4 months, and the median dose just above 3 g prednisolone. Patients who stayed in remission during the follow-up received a significantly higher start dose and total dose of prednisolone in the treatment episode than patients who had a relapse. In 25 patients treatment with doses equal to or above 75 mg of prednisolone was continued beyond 10 days, and 11 patients experienced remission whereas 14 patients had surgery performed. Orally administered corticosteroids produce results comparable to those obtained after the previously suggested intravenous regimen.     

The Impact of IFNL4 rs12979860 Polymorphism on Spontaneous Clearance of Hepatitis C; A Case-Control Study

Background:

About 30% of individuals with hepatitis C virus (HCV) infection are able to clear HCV spontaneously. Differences in host genetics affect the outcome of HCV infection. Single nucleotide polymorphisms (SNPs) of the Interferon lambda (IFNL) genes were associated with spontaneous and treatment-induced clearance of HCV infection.

Objectives:

The aim of this study was to evaluate the association between the IFNL4 rs12979860 SNP and spontaneous clearance of HCV infection in Iranian population.

Materials and Methods:

A case-control study was designed on 91 cases with spontaneous HCV infection clearance and 259 patients with persistent HCV infection as the control group. The rs12979860 SNP was assessed as the most common IFNL polymorphism by PCR-RFLP method.

Results:

Distribution of rs12979860 CC genotype in the spontaneous clearance group was around two folds of its distribution in chronic hepatitis C group (P < 0.001, OR = 4.09, 95% CI = 2.44-6.86).

Conclusions:

The rs12979860 SNP was observed as a strong host genetic factor associated with spontaneous clearance of hepatitis C infection.     

A cohort study for the derivation and validation of a clinical prediction scale for hospital-onset Clostridium difficile infection

OBJECTIVE:

To develop and validate a clinical prediction scale for hospital-onset Clostridium difficile infection (CDI).

METHODS:

A community-based, 360-bed hospital located in the suburbs of a metropolitan area in the United States served as the setting for the present retrospective cohort study. The cohort consisted of patients admitted to the adult medical service over a six-year period from October 2005 to September 2011. The cohort was divided into derivation (October 2005 to September 2009) and validation (October 2009 to September 2011) groups. The primary outcome measure was hospital-onset CDIs identified as stool positive for C difficile after 48 h of hospital admission ordered for new-onset unformed stool by the treating physician.

RESULTS:

In the derivation phase, 35,588 patients were admitted to the medical service and 21,541 stayed in hospital beyond 48 h. A total of 266 cases of CDI were identified, 121 of which were hospital onset. The developed clinical prediction scale included the onset of unformed stool (5 points), length of hospital stay beyond seven days (4 points), age >65 years (3 points), long-term care facility residence (2 points), high-risk antibiotic use (1 point) and hypoalbuminemia (1 point). The scale had an area under the receiver operating curve (AUC) of 0.93 (95% CI 0.82 to 0.94) in predicting hospital-onset CDI, with a sensitivity of 0.94 (95% CI 0.88 to 0.97) and a specificity of 0.80 (95% CI 0.79 to 0.80) at a cut-off score of 9 on the scale. During the validation phase, 16,477 patients were admitted, of whom 10,793 stayed beyond 48 h and 58 acquired CDI during hospitalization. The predictive performance of the score was maintained in the validation cohort (AUC 0.95 [95% CI 0.93 to 0.96]) and the goodness-to-fit model demonstrated good calibration.

CONCLUSION:

The authors developed and validated a simple clinical prediction scale for hospital-onset CDI. This score can be used for periodical evaluation of hospitalized patients for early initiation of contact precautions and empirical treatment once it is validated externally in a prospective manner.     

The Effect of Proctocolectomy on Serum Antibody Levels against Cow's Milk Proteins in Patients with Chronic Ulcerative Colitis,with Special Reference to Liver Changes

Aitola PT, Soppi ET, Halonen PJ, Laine ST, Matikainen MJ. The effect of proctocolectomy on serum antibody levels against cow's milk proteins in patients with chronic ulcerative colitis, with special reference to liver changes. Scand J Gastroenterol 1994;29:646-650

Background: The levels of antibodies against cow's milk proteins in ulcerative colitis (UC) were used to study whether mucosal inflammation leads to immune recognition, as a marker of enhanced permeability, of dietary proteins. A further purpose was to study the effect of proctocolectomy on the serum antibody levels against cow's milk proteins and their relation to biochemical and histologic liver abnormalities associated with ulcerative colitis.

Methods: Serum antibody levels against six cow's milk proteins, α-casein, α-lactalbumin (LA), β-lactoglobulin A (LGA), β-lactoglobulin B (LGB), bovine serum albumin (BSA), and whole milk powder (MP) were determined before and after (mean, 24 months) proctocolectomy in 15 patients with ulcerative colitis. Simultaneously, serum liver enzymes were analyzed. A liver biopsy specimen was also obtained at proctocolectomy.

Results: Before proctocolectomy IgA antibody levels were significantly increased against all antigens except BSA. Increased levels of IgM antibodies against LGA, LGB, and BSA were also detected. IgG antibodies were significantly increased only against LGA. After proctocolectomy IgA and IgM antibody levels decreased significantly (p < 0.05) against LGA, LGB, and LA, whereas IgG antibodies increased significantly (p < 0.01). In the patient group with abnormal liver histology (n equals; 9) the IgA antibodies to all cow's milk proteins were significantly higher (p < 0.02) than in the group with normal liver histology both before and after proctocolectomy. The IgA antibody levels showed a significant positive correlation with alanine amino-transferase and gamma-glutamyltransferase (r value from 0.460 to 0.721, p value from <0.05 to <0.01), but not with alkaline phosphatase. Conclusions: These results suggest that the inflamed mucosa in UC allows the antigenic contents of the bowel to escape. Proctocolectomy alters the antibody levels against certain milk proteins, which may serve as a model to suggest that proctocolectomy, probably by eliminating inflammation, may have positive effects by reducing the foreign pathogenic antigen and immune complex load.