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Approach to patients with multiple relapses of antibiotic-associated pseudomembranous colitis
Abstract
Twenty-two patients with multiple relapses of antibiotic-associated pseudomembranous colitis underwent a tapering dose of oral vancomycin for 21 days and a pulse dose of vancomycin for 21 days. In follow-up ranging from 2-12 months with a mean of 6 months, all patients have been without recurrence of the antibiotic-associated pseudomembranous colitis.
... Treatment guidelines recommend extended vancomycin courses such as a standard course followed by a taper, pulse, or a taper-and-pulse to reduce the incidence of CDI recurrence based on small individual studies [11,12]. The rationale of extended durations of vancomycin is to suppress Clostridioides difficile vegetative forms followed by an extended regimen either as a taper or pulse or taper-andpulse to potentially allow reestablishment of nonpathogenic flora. ...
... The mean resolution rate for this regimen was 54% (11/26 95% CI 0-100%) with significant difference between the studies (range 26-86%) and significant heterogeneity (I 2 = 86%) ( Figure 2B). The median of prior CDI episodes was 3 (range 1- [21], and the mean number was 3.2 ± 2.1 (range [1][2][3][4][5][6][7][8][9][10][11][12][13][14] in the other study [12]. ...
... Where specified, the follow-up duration varied between these studies, ranging from 56 days [25], to 120 days [22] and a mean of 90 days [23] or 180 days [11]. The definition of recurrence also varied, where two studies defined it as a new episode of lab confirmed CDI with diarrhoea within 120 days after completion of the first course of treatment [22,26], and other two defined it as an episode occurring within 8 weeks after the completion of treatment [23,24]. ...
Background
Vancomycin is the drug of choice for treating Clostridioides difficile infection (CDI). We compare CDI resolution with vancomycin taper, pulse and taper-and-pulse regimens.
Methods
We searched Medline, Embase, Cochrane and Scopus through October 9th, 2020. Taper regimen was defined as dose reduction over time; pulse was a regimen less frequent than daily. Studies assessing CDI resolution rates were included. Meta-analyses for resolution rates were performed using weighted proportion ratios (WPR).
Results
Ten studies with 675 patients treated with the vancomycin regimens were included. Resolution rates were 83% (212/266, 95% CI 69-94%, I² = 85%) for taper-and-pulse, 68% (264/383, 95% CI 57-78%, I² = 72%) for taper alone, and 54% (11/26 95% CI 0-100%, I² = 86%) for pulse alone regimens. Taper-and-pulse was superior to taper alone (WPR 83% vs 68%, p<0.0001) and pulse alone (WPR 83% vs 54%, p<0.0004), no significant difference between taper alone or pulse alone (WPR 68% vs 54%, p=0.1).
Conclusions
Limitations of our analysis are a small number of included studies and heterogeneity. Vancomycin taper-and-pulse seems superior to pulse alone or taper alone for recurrent CDI. A randomized controlled trial comparing vancomycin taper-and-pulse to fidaxomicin and microbiome restoration is needed.
... Tedesco and colleagues 14 were the first to report outcomes following a vancomycin taper in 22 patients (14 female) with 2-5 relapses of antibiotic-associated pseudomembranous colitis (AAPMC) or CDI. The mean age among the patients was 59 years and diverticulitis was noted in 82% of patients. ...
... Reviewed literature identified three case series [14][15][16] and two clinical trials 17,18 encompassing a total of 174 patients treated with an evaluable EDV regimen, of these only 31 patients were included in randomized trials. The largest report was a case series covering 100 patients. ...
... The most frequently used regimens followed a taper and pulse combination similar to that recommended in the IDSA guidelines, which appears to be based on the original work of Tedesco and colleagues but referenced McFarland and colleagues. 13,14,16,18 Response rates varied greatly with an initial published case series 14 reporting success rates of 100% to as low as 26% in a more recent randomized trial. 17 Duration of therapy ranged from 21 days 17 to exceeding 60 days. ...
Clostridium difficile infections have a high recurrence rate following acute treatment. Extended duration vancomycin (EDV) is a mainstay for the treatment of recurrent Clostridium difficile infections (rCDI). Clinical disease guidelines recommend a variety of different vancomycin treatment regimens though based on weak, low-quality evidence. Patients typically receive an initial vancomycin treatment course of 7–14 days for the acute infection, followed by an extended duration vancomycin course. Multiple publications on the utility of EDV regimens have been published but few include reported effectiveness outcomes associated with a prescribed treatment regimen. The purpose of this review is to evaluate the safety and efficacy data on extended duration vancomycin regimens used in recurrent clostridium treatment. Five articles, three case series and two randomized open-label clinical trials, were identified which included both elements. Outcomes were evaluable in 174 patients, 31 from randomized trials, with prior average recurrent episodes ranging from 3 to 4. Vancomycin dose ranged from 3500 to >6800 mg with therapy durations extending from 21 days to over 60 days. Follow-up duration ranged from 10 weeks to 12 months. Case series reported success rates for EDV in rCDI from 61% to 100%, while randomized trials found lower success rates from 26% to 58%. Taper and pulse regimens reported superior outcomes compared to pulse-only regimens, 58–100% versus 26–81%, respectively. Comparative EDV data is limited. Current available data supports an EDV regimen which includes both a daily dosing taper followed by an every 48 or 72 h pulse.
... The current Infectious Diseases Society of America (IDSA)/ Society for Healthcare Epidemiology of America (SHEA) guidelines for treating recurrent Clostridium difficile infection (rCDI) recommend treatment of the first recurrence with the same regimen used for treatment of the initial episode with a caveat of using oral vancomycin if the recurrence is severe, and treating further recurrences with oral vancomycin in a tapered and pulsed fashion [1]. Despite this recommendation, very few studies of vancomycin taper and/or pulse dosing have been reported that would allow estimation of optimal regimens and expected outcomes [2,3]. Our clinic has been a referral center for patients with rCDI for the last decade. ...
... Factors associated with prescribing QOD + Q3D over QOD only were older age and prior administration of a vancomycin taper and/or pulse regimen. Previous observational studies have reported outcomes for vancomycin tapers, pulse regimens, or combined taper and pulse regimens for rCDI, although the number of patients was small and the duration of follow-up was variable [2,3]. In an uncontrolled prospective study, Majors and Ellis employed a VAN-TP regimen of 6 weeks' duration ending with QOD dosing in patients with initial CDI episodes in an attempt to reduce hospital readmissions for rCDI [11]. ...
... Our finding of improved cure rates with QOD + Q3D dosing over QOD dosing is consistent with the hypothesis that pulse dosing promotes a cyclical decrease in spore burden while also permitting the reestablishment of normal microbiota [2,12]. Extension of the pulse regimen from QOD to Q3D might promote more thorough clearance of spores by allowing more time between dosing for spore germination and eradication of the resultant vegetative organisms. ...
We retrospectively studied vancomycin taper and pulse treatment on 100 consecutive, evaluable patients with recurrent C. difficile infection. Following taper to once-daily vancomycin dosing, 22 of 36 patients (61%) who received every-other-day (QOD) and 50 of 64 (81%) who received QOD followed by every-third-day dosing were cured (P = 0.03).
... The latest Infectious Disease Society of America (IDSA) guidelines recommend tapered and pulsed vancomycin therapy for the first recurrence [1]. A recent systematic review evaluated two randomized open-label clinical trials [12,13] and three case series [14][15][16]. Two of these case series [14,16] and one of these clinical trials [13] used tapered and pulsed regimen, whereas the other case series [15] and clinical trial [12] utilized pulsed only regimen. ...
... A recent systematic review evaluated two randomized open-label clinical trials [12,13] and three case series [14][15][16]. Two of these case series [14,16] and one of these clinical trials [13] used tapered and pulsed regimen, whereas the other case series [15] and clinical trial [12] utilized pulsed only regimen. Authors concluded that the reviewed literature supports extended duration tapering and pulsed vancomycin therapy for recurrent CDI [17]. ...
Recurrent Clostridium difficile infection (CDI) is a perpetual problem that leads to increased economic burden, higher healthcare cost, and significant morbidity and mortality. Its treatment remains a challenge. While various treatment approaches have been attempted with different levels of success, robust data establishing the superiority of one approach over the others is lacking. In this article, we review the current evidence pertaining to conventional pharmacological treatment as well as fecal microbiota transplantation (FMT) as a novel, rapidly emerging treatment modality for recurrent CDI.
... The probabilities and costs used are presented in Table 1. All probabilities were obtained from the published literature 10,16,[23][24][25][26][27][28][29][30][31][32][33][34][35][36] with weighted averages calculated from pooled data extracted from the individual studies. Randomized controlled trials and meta-analyses were used whenever possible. ...
... Probabilities associated with various vancomycin pulse or taper regimens were pooled due to the limited number of studies available. [28][29][30] The probability of cure with FMT was based on overall success rates reported with multiple instillations. 16 Decision tree for primary model of initial treatment strategy for mild-to-moderate Clostridium difficile infections in hospitalized patients. ...
Purpose:
The cost-effectiveness of initial treatment strategies for mild-to-moderate Clostridium difficile infection (CDI) in hospitalized patients was evaluated.
Methods:
Decision-analytic models were constructed to compare initial treatment with metronidazole, vancomycin, and fidaxomicin. The primary model included 1 recurrence, and the secondary model included up to 3 recurrences. Model variables were extracted from published literature with costs based on a healthcare system perspective. The primary outcome was the incremental cost-effective ratio (ICER) between initial treatment strategies.
Results:
In the primary model, the overall percentage of patients cured was 94.23%, 95.19%, and 96.53% with metronidazole, vancomycin, and fidaxomicin, respectively. Expected costs per case were $1,553.01, $1,306.62, and $5,095.70, respectively. In both models, vancomycin was more effective and less costly than metronidazole, resulting in negative ICERs. The ICERs for fidaxomicin compared with those for metronidazole and vancomycin in the primary model were $1,540.23 and $2,828.69 per 1% gain in cure, respectively. Using these models, a hospital currently treating initial episodes of mild-to-moderate CDI with metronidazole could expect to save $246.39-$388.37 per case treated by using vancomycin for initial therapy.
Conclusion:
A decision-analytic model revealed vancomycin to be cost-effective, compared with metronidazole, for treatment of initial episodes of mild-to-moderate CDI in adult inpatients. From the hospital perspective, initial treatment with vancomycin resulted in a higher probability of cure and a lower probability of colectomy, recurrence, persistent recurrence, and cost per case treated, compared with metronidazole. Use of fidaxomicin was associated with an increased probability of cure compared with metronidazole and vancomycin, but at a substantially increased cost.
... 5,11 One of these approaches for treatment of recurrence is the use of a slowly-tapered vancomycin regimen over several weeks following a standard course of therapy. [12][13] The purpose of this multicenter, clinical administrative database study was to compare the outcomes of an oral vancomycin course without taper versus an oral vancomycin course with taper for treatment of recurrent CDI. ...
... Tedesco and colleagues (1985) reported no further recurrences in a case series of 22 patients with multiple CDI recurrences who received tapering doses of vancomycin over 42 days after a follow-up ranging from 2 to 12 months. 12 More recently, McFarland and colleagues (2002) described various strategies for treating recurrent CDI in a post hoc analysis arising from two multicenter, double-blind, placebo-controlled trials evaluating a Saccharomyces boulardii preparation. 13 Recurrence rates for "low" (n=48), "medium" (n= 14), and "high" (n=21) non-taper oral vancomycin dose groups were 54%, 71%, and 43%, respectively, while a To our knowledge, the current project is the first robust attempt to compare the use of a prolonged vancomycin taper to a standard course of vancomycin without taper, utilizing a propensity score-matched methodology to produce two groups with similar baseline demographics, comorbidities, laboratory abnormalities, and severity of disease. ...
Background
This study was conducted to compare clinical outcomes of oral vancomycin courses without taper versus oral vancomycin courses with taper for treatment of recurrent Clostridium difficile infection (CDI).
Methods
This investigation was a multicenter, retrospective, propensity-score matched analysis study utilizing a Veterans Health Administration national clinical administrative database. Adult patients treated for recurrent CDI from any Veterans Affairs Medical Center (VAMC) between June 1, 2011 and October 31, 2016 were included if treated with oral vancomycin with or without a tapering regimen. The two groups were matched by next nearest approach from a propensity score formula derived from independent variables associated with the selection of a taper regimen
Results
Propensity score matching resulted in two well-matched groups consisting of 226 episodes of patients treated with a vancomycin taper regimen and 678 episodes treated by vancomycin regimen without taper. No difference was found for the primary outcome of 180-day recurrence (59/226 [26.1%] for taper regimens versus 161/678 [23.8], p=.48). A secondary outcome of 90-day all-cause mortality met statistical significance, favoring a taper regimen (5.31% vs 9.29%, p =.049), however secondary outcomes of 90-day recurrence and 180 day all-cause mortality were not different.
Conclusions
Vancomycin taper regimens did not provide benefit over vancomycin regimens without taper in preventing additional CDI recurrence in patients with first or second recurrent episodes in this propensity score-matched analysis.
... In mid-February 2015, after discussion of the high proportion of severe cases and recurrences in a committee created exclusively for the current outbreak, a new treatment approach was proposed; all first episodes would be treated with a prolonged vancomycin taper or with fidaxomicin. As previously reported [10,11], prolonged or pulsed vancomycin therapy initiated with a high-dose regimen seemed to be effective in reducing recurrences, although randomized prospective studies of these regimens have never been performed. The prolonged vancomycin taper consisted of 500 mg qid during week 1, 250 mg qid during week 2, 125 mg qid during week 3, and a pulsed dose of 125 mg qid every 2 days for a further 4 weeks. ...
... An equally possible alternative theory is that tapering and pulsed dosing are sufficient to suppress growth of Clostridium difficile while allowing the microbiota to recover [34]. In a study from 1985, prolonged tapering of high-dose vancomycin was reported to be successful for treating recurrences of CDI [11]. Ours is the first study in which this same regimen was used to treat first episodes of CDI-027 and led to a reduction in cases and recurrences. ...
An outbreak of Clostridium difficile infection (CDI) caused by ribotype 027 (B1/NAP1) began in our hospital in November 2014, and produced 141 episodes in the following months. The aim of this study is to describe this outbreak, assess risk factors for recurrence of CDI-027 and to analyze the implementation of a novel treatment strategy. This is a prospective study of all patients with CDI-027, from November 2014 to November 2015. The epidemiological data were collected daily for each patient. We compared clinical characteristics and treatment between patients with and without recurrence of CDI-027. Interestingly, liver cirrhosis was present in 22% of the patients, and most of them received prophylaxis for hepatic encephalopathy with rifaximin. Patients were also taking antimicrobial drugs (93.6%) and proton pump inhibitors (80.1%). Overall, 27 (23.5%) patients had a first recurrence of CDI-027. Liver cirrhosis increased the risk of recurrence (44.4% vs 14.8%). Patients treated with a prolonged oral vancomycin regimen vs the conventional regimen (oral metronidazole or 10 days of vancomycin) had fewer recurrences (8.6 versus 44.7% [p ≤ 0.01]; OR, 0.91; 95% CI, 0.028-0.294) and less attributable mortality (0% versus 7.1%; p = 0.058). We report an outbreak of CDI-027, mainly in patients with liver cirrhosis. Recurrence of CDI-027 was more common in those patients. A novel approach involving high-dose prolonged vancomycin taper as a first-line treatment, together with a bundle of outbreak measures, seemed to reduce the number of cases of CDI-027, recurrences, and attributable mortality. Nevertheless, this approach warrants further investigation.
... Guidelines published by PHE 1 list extended vancomycin as an option for patients with multiple recurrences; however, no specific regimen is recommended. Tedesco et al. 2 evaluated a different (lower dose) vancomycin extended-dosing regimen to that outlined by PHE guidelines and reported a high response rate in 22 patients with CDI. Further studies are required to provide definitive evidence of the efficacy of such regimens. ...
... Two vancomycin extended-dosing regimens outlined by Tedesco et al. 2 and PHE guidelines 1 [comprising totals of 7 g (lower dose 2 ) and 9.5 g (higher dose 1 ) vancomycin, respectively], were investigated using an in vitro gut model of CDI to determine the effects on the gut microbiota, C. difficile and VRE populations. ...
Objectives:
Effects of two vancomycin extended-dosing regimens on microbiota populations within an in vitro gut model of simulated Clostridium difficile infection (CDI) were evaluated.
Methods:
Two chemostat gut models were inoculated with faecal emulsion and clindamycin instilled to induce CDI. Simulated CDI was treated with vancomycin (125 mg/L four times daily, 7 days) followed by different vancomycin dosing extensions totalling 7 g (lower dose) or 9.5 g (higher dose) over 6 weeks in Model A and Model B, respectively. Microbiota populations, C. difficile vegetative cells and spores, cytotoxin, antimicrobial concentrations and vancomycin-tolerant enterococci (VTE) were measured every 1-2 days.
Results:
In both models, vancomycin instillation caused a rapid decline in vegetative cells and cytotoxin, and declines in the Bacteroides fragilis group, bifidobacteria and clostridia populations to the lower limit of detection. Bifidobacteria failed to recover for the remainder of the experiment. B. fragilis group populations recovered to pre-dosing levels during the dosing extension in Model A and after dosing ceased in Model B. Recurrent CDI was observed on the penultimate day of Model B, but not Model A. VTE were observed throughout the experiment in both models, but populations increased during vancomycin instillation and post-vancomycin instillation.
Conclusions:
The two vancomycin extended-dosing regimens were efficacious in initial treatment of simulated CDI. Both had a prolonged deleterious effect on the indigenous gut microbiota, a factor that may contribute to recurrence; recurrence was observed only in Model B, although the potential for vegetative regrowth within Model A cannot be excluded. Vancomycin exposure appeared to select for VTE populations.
... The tapering dose may also provide an opportunity for the restoration of healthy microbiota of the gut. Tedesco et al., in 1985, reported an absence of relapse during a 2-to 12-month follow-up of 22 patients with relapsing CDI who were treated with either tapered or pulsed doses of vancomycin over a 21-day period [32]. ...
... The tapering dose may also provide an opportunity for the restoration of healthy microbiota of the gut. Tedesco et al., in 1985, reported an absence of relapse during a 2-to 12-month follow-up of 22 patients with relapsing CDI who were treated with either tapered or pulsed doses of vancomycin over a 21-day period [32]. ...
Clostridium difficile infection (CDI) is a potentially fatal illness, especially in the elderly and hospitalized individuals. The recurrence and rates of CDI are increasing. In addition, some cases of CDI are refractory to the currently available antibiotics. The search for improved modalities for the management of primary and recurrent CDI is underway. This review discusses the current antibiotics, fecal microbiota transplantation (FMT) and other options such as immunotherapy and administration of non-toxigenic Clostridium difficile (CD) for the management of both primary and recurrent CDI.
... 60,61 In case of relapsing Clostridium difficile infections, vancomycin in combination with rifampin is recommended. 62 There is not muchdocumented data on the infections due to endoscopy. But fatal infections have been reported after surgical procedures 63 While administering the antibiotics, certain criteria such as the nature of the organism, and the efficacy of the antibiotic administered should be taken into consideration. ...
Antibiotics are the class of medications intended to treat and prevent bacterial infections by predominantly acting on bacteria by either making it difficult for the organism to grow and multiply or by killing them. They play a significant role in modern healthcare in improving patient health outcomes by reducing infective complications. In the emerging use of antibiotics, the pre and post-antibiotic regimen has a huge role in reducing the post-surgical complication which thereby increases the quality of life in surgical patients. Due to the irrational use of antibiotics, there is a rapid increase in the resistance to antimicrobial agents. Therefore, the rational operative antibiotic usage depends upon the factors like skin incision time; duration and frequency of administration; immunological status of the patient. Thus the importance of operative prophylaxis antibiotics has been discussed as a part of preventing surgical complications such as surgical site infections (SSI), antimicrobial resistance, septicaemia and adverse events during the patient's stay. This review is focused on the importance of prophylactic antibiotics, especially on major clean or clean-contaminated open surgeries which include cardiac surgery, gastro surgery and neurosurgery.
... Calculated after 90 days, the treatment effect was superior (cure rate 81%) in those who received treatment every three days compared with those who received treatment every other day (cure rate 61%). In a series of 22 patients, most of whom had three or more recurrences, the vancomycin 125%  4 daily cure rate was reduced to 125 mg  2 daily for one week, 125 mg  1 daily for one week and then pulse treatment with 125 mg every two days for a week and lastly pulse treatment with 125 mg every three days for one week [34]. Conversely, a propensity score-matched cohort study with patients with first or second recurrence of CDI found no difference in recurrence rate after vancomycin with (n ¼ 226) or without tapering (n ¼ 678). ...
Aim: This Danish national guideline describes the treatment of adult patients with Clostridioides (formerly Clostridium) difficile (CD) infection and the use of faecal microbiota transplantation (FMT). It suggests minimum standard for implementing an FMT service.
Method: Four scientific societies appointed members for a working group which conducted a systematic literature review and agreed on the text and recommendations. All clinical recommendations were evalluated for evidence level and grade of recommendation.
Results: In CD infection, the use of marketed and experimental antibiotics as well as microbiota-based therapies including FMT are described. An algorithm for evaluating treatment effect is suggested. The organisation of FMT, donor recruitment and screening, laboratory preparation, clinical application and follow-up are described.
Conclusion: Updated evidence for the treatment of CD infection and the use of FMT is provided.
... One of the main problems associated with CDI is the high incidence of recurrence (in 15 to 50% of cases) following initial success with antibiotic treatment 35 . Relapsing CDI occurs due to the presence of C. difficile spores that germinate in the gut into vegetative cells that colonize the intestine and subsequently produce toxins 36,37 . Recurrence of infection occurs in approximately 20% of patients 15,38,39 . ...
Clostridioides difficile infections (CDIs) are an urgent public health threat worldwide and are a leading cause of morbidity and mortality in healthcare settings. The increasing incidence and severity of infections combined with the scarcity of effective anti-CDI agents has made treatment of CDI very challenging. Therefore, development of new, effective anticlostridial agents remains a high priority. The current study investigated the in vivo efficacy of auranofin in a CDI hamster model. All hamsters treated with auranofin (5 mg/kg) survived a lethal challenge with C. difficile . Furthermore, auranofin (5 mg/kg) was as effective as vancomycin, the drug of choice for treatment of CDIs, against relapsing CDI. Furthermore, auranofin (5 mg/kg) generated a 3.15-log 10 reduction (99.97%) in C. difficile count in the cecal contents of hamsters. These results indicate that auranofin warrants further investigation as a new agent to replenish the pipeline of anti-CDI therapeutics.
... Diverticular disease of the colon affects a large portion of the population especially the elderly with an estimated incidence of 50-66% in people over the age of 80 [8]. In 1980s, Tedesco FJ et al. [9] suggested colonic diverticula serve as a reservoir for Clostridioides difficile after the author noted a high prevalence of diverticulosis in patients with CDI. Buchner et al. reported an increased risk for CDI in veteran patients with a history of diverticulitis [10]. ...
Background: Clostridioides difficile infection (CDI) is one of the most common healthcare-associated infections. It contributes to significant morbidity and mortality among hospitalized patients in the United States. Prior studies suggest worse outcomes of CDI in patients with diverticulitis and increased risk for recurrent CDI. We conducted this study to evaluate the outcomes of CDI in patients with diverticular disease from a nationwide data sample (2012–2015).
Methods: The National Inpatient Sample (NIS) database between January 2012 and September 2015 was queried for CDI admissions using the International Classification of Diseases, Ninth Edition, Clinical Modification [ICD-9-CM] codes 008.45, 562.11, 562.10, 562.12, and 562.13 for diagnoses of CDI and diverticular disease.
Results: The study included 1,327,595 patients who were admitted between 2012 and 2105 for CDI. Out of all of the patients, 84,170 (6.34%) had a concurrent diagnosis of diverticular disease. After adjusting for confounding variables, the in-hospital mortality was lower [odd ratio (OR): 0.48, 95% CI: 0.44–0.52, p < .001] for patients with diverticular disease. The length of stay (LOS) was longer [10.5 versus 9.3 days, p < .001] and mean cost of hospitalization was significantly higher in patients without a history of diverticular disease.
Discussion: In a nationwide population study, admissions with CDI, patients with a concurrent diagnosis of diverticular disease had lower in-hospital mortality. The observed results are different from prior studies and might be attributed to a higher burden of normal flora in those patients and increased use of antibiotic stewardship program across many hospitals nationwide.
... Although it is suspected that noncompliance by patients and misdiagnosis contribute to recurrence, the true etiology of recurrence remains unknown.Once the diagnosis has been confirmed, the case is managed either by tapered (125 mg four times a day for one week, then twice a day for one week, once a day for one week, every other day for one week, and finally, every three days for one week), or pulse vancomycin regimen (given on alternate days initially, then every 3 days and so on) and should last several weeks on the basis of the concept that persistent spores convert to toxin producers and are killed when antibiotics are given repeatedly over time. [77,78]. ...
Clostridium difficile was thought to be nonpathogenic until 1978, when Bartlett et al. identified C. difficile as the source of cytotoxin in the stools of patients with pseudomembranous colitis, a disorder frequently associated with antimicrobial use C. difficile is responsible for both hospital-acquired and community-acquired diarrhea. Clostridium difficile is transmitted via the fecal-oral route, disruption of the gut flora, typically by antibiotics, allows C. difficile to proliferate, thus resulting in infection C. difficileexerts its pathogenic effect mainly through the production of two exotoxins, toxin A and B. Usually, exposure to both antimicrobials andtoxin-producing C. difficile strains is necessary for the development of CDI. Host factors may be as important. CDI has a wide range of manifestations, causing a self-limited mild diarrheal illness to a fulminant life-threatening colitis. The two main risk factors for CDI are antibioticexposure and age older than 65 but other factors shouldalso be considered like the use of laxatives, proton pump inhibitors or H2 histamine as gastric protection, chemotherapy, renal failure, gastrointestinal surgery, nasogastric tube, mechanical ventilation, prolonged hospital stay. The most widely used diagnostic test for the diagnosis of CDI is the enzyme immunoassay (EIA) for toxin A or toxins A and B. Other methods include:an antigen test that detects the mitochondrial enzyme glutamate dehydrogenase (GDH) within C. difficile, used for screening, stool culture, the cytotoxicity cell assay, another highly sensitive and specific method is polymerase chain reaction(PCR), sensitivity being higher than 90% and specificity of 100%. Colonoscopy and flexible sigmoidoscopyalso used in certain situations, abdominal X-ray is used in cases of ileus or toxic megacolon.
... Vancomycin continues to be used for treatment of the first recurrence, and for those with a second or greater recurrence, a vancomycin taper or taper-pulse therapy has been used (57,62). However, randomized controlled trials to evaluate this strategy are not available. ...
... McFarland et al. 76 were able to reduce the frequency of relapse to 14.3% by a pulsed regime and up to 31% by using a tapered strategy. 78 The pulsed strategy proposed a standard VAN course over 10 days followed by a course of 125 mg VAN every 2-3 days for 10 doses. Of the multiple strategies used for tapering VAN, the IDSA guidelines 2010 recommended stepping down to 125 mg twice daily for a week after the regular 10 days of VAN, followed by 125 mg once daily for a week which is then followed by pulse of 125 mg every 2-3 days for 2-8 weeks. ...
Clostridium difficile-associated disease continues to be one of the leading health concerns worldwide. C. difficile is considered as a causative agent of nosocomial diarrhea that causes serious infection, which may result in death. The incidences of C. difficile infection (CDI) in developed countries have become increasingly high which may be attributed to the emergence of newer epidemic strains, extensive use of antibiotics, and limited alternative therapies. The available treatment options against CDI are expensive and promote resistance. Therefore, there is urgent need for new approaches to meet these challenges. This review discusses the current understanding of CDI, the existing clinical treatment strategies and future potential options as antidifficile agents based on the available published works.
... Vancomycin taper resulted in recurrence in 41.7% of our patients. This proportion is higher than the 0-30% recurrence rate reported in 2 older observational studies upon which current treatment recommendations are based [28,32]. ...
Background:
Fecal transplantation (FT) is a promising treatment for recurrent Clostridium difficile infection (CDI), but its true effectiveness remains unknown. We compared 14 days of oral vancomycin followed by a single FT by enema with oral vancomycin taper (standard of care) in adult patients experiencing acute recurrence of CDI.
Methods:
In a phase 2/3, single-center, open-label trial, participants from Ontario, Canada, experiencing recurrence of CDI were randomly assigned in a 1:1 ratio to 14 days of oral vancomycin treatment followed by a single 500-mL FT by enema, or a 6-week taper of oral vancomycin. Patients with significant immunocompromise, history of fulminant CDI, or irreversible bleeding disorders were excluded. The primary endpoint was CDI recurrence within 120 days. Microbiota analysis was performed on fecal filtrate from donors and stool samples from FT recipients, as available.
Results:
The study was terminated at the interim analysis after randomizing 30 patients. Nine of 16 (56.2%) patients who received FT and 5 of 12 (41.7%) in the vancomycin taper group experienced recurrence of CDI, corresponding with symptom resolution in 43.8% and 58.3%, respectively. Fecal microbiota analysis of 3 successful FT recipients demonstrated increased diversity. A futility analysis did not support continuing the study. Adverse events were similar in both groups and uncommon.
Conclusions:
In patients experiencing an acute episode of recurrent CDI, a single FT by enema was not significantly different from oral vancomycin taper in reducing recurrent CDI. Further research is needed to explore optimal donor selection, FT preparation, route, timing, and number of administrations.
Clinical trials registration:
NCT01226992.
... At present, metronidazole and vancomycin are mainly administered for treating CDI. However, up to 25% of patients treated for CDI experience recurrences after discontinuing antibiotic therapy (Bartlett et al., 1980;Tedesco et al., 1985;Leffler and Lamont, 2009;Surawicz et al., 2013). The increase in treatment failure or multiple relapses have raised a concern. ...
Sortases function as cysteine transpeptidases that catalyze the covalent attachment of virulence-associated surface proteins into the cell wall peptidoglycan in Gram-positive bacteria. The substrate proteins targeted by sortase enzymes have a cell wall sorting signal (CWSS) located at the C-terminus. Up to date, it is still not well understood how sortases with structural resemblance among different classes and diverse species of bacteria achieve substrate specificity. In this study, we focus on elucidating the molecular basis for specific recognition of peptide substrate PPKTG by Clostridium difficile sortase B (Cd-SrtB). Combining structural studies, biochemical assays and molecular dynamics simulations, we have constructed a computational model of Cd-SrtBΔN26–PPKTG complex and have validated the model by site-directed mutagensis studies and fluorescence resonance energy transfer (FRET)-based assay. Furthermore, we have revealed that the fourth amino acid in the N-terminal direction from cleavage site of PPKTG forms specific interaction with Cd-SrtB and plays an essential role in configuring the peptide to allow more efficient substrate-specific cleavage by Cd-SrtB.
... Tedesco et al [63] [11] , 83 patients treated with 10-14 d course of vancomycin had an average relapse rate of 55% (range 42%-71%, depending on vancomycin dosing). Twentynine patients were treated with a vancomycin taper over an average of 21 d and 31% relapsed. ...
... Management of the patient with multiple relapses can be very difficult since no single therapeutic measure is uniformly effective in pre venting disease relapse. Traditional ap proaches to treating patients with recur ring C. difficile colitis have included re peated courses of antibiotics, addition of resins such as cholestyramine and colestipol, and longer tapering doses or pulse doses of vancomycin (Bartlett, 1983; Tedesco et al., 1985). The variety of therapies tried in treating patients with relapse of C. dif ficile-associated intestinal disease attest to the fact that no single therapeutic measure is uniformly effective in pre venting disease relapse. ...
... In this situation fidaxomycin (200 mg twice daily for 10 days) or vancomycin (125 mg four times daily for 10 days) followed by either a pulsed or tapered strategy is recommended. Up to now, there is no single strategy that can be recommended; however, McFarland et al. [35] could reduce the frequency of relapse to 14.3% by a pulsed regime up and to 31% by using a tapered strategy [37]. The pulsed strategy proposed requires a standard vancomycin course over 10 days followed by 125 mg vancomycin every 2-3 days for 10 doses. ...
Clostridium difficile infections (CDI) are increasingly important in patients with antibiotic treatments, ranging from mild, self-limiting to severe, life-threatening disease. Currently, diagnostic algorithms and treatment guidelines are being adapted to novel tests and therapeutic options for recurrent CDI.
A systematic literature search using the terms 'Clostridium difficile' and 'treatment' was carried out. Current guidelines are being discussed from a clinical point of view.
State-of-the-art diagnostics for C. difficile diagnosis rely on the patient's history, clinical symptoms, and laboratory examination of stool. Recommendations are in favour of glutamate dehydrogenase (GDH) screening tests and confirmatory detection of C. difficile toxin genes (polymerase chain reaction (PCR)). Therapeutic strategies depend on disease severity (mild vs. severe) and endorse metronidazole and vancomycin as well as fidaxomycin for recurrent disease. In very severe cases, surgical therapy is recommended. For relapsing diseases, faecal transfer is considered as a therapeutic option if available.
Current guidelines have been adapted to new pathways in diagnosing CDI and have included statements on novel therapeutic options such as fidaxomycin and faecal transplant for recurrent disease. Depending on the severity of the disease, standard therapy with either metronidazole or vancomycin is recommended.
... Irrational use of antibiotics is one of the main causes of PMC (15)(16)(17) and once PMC is suspected, the original use of antibiotics should be immediately suspended. Patients with mild symptoms may recover after stopping antibiotics. ...
Pseudomembranous colitis (PMC) occurs mainly in adults and is believed to be caused almost exclusively by toxins produced by Clostridium difficile. Colonoscopy found that PMC occurs mainly in the colon, sigmoid colon and rectum in up to 80% ~ 100% of cases. Colonoscopy is simple and fast. It has the significance of making a definite diagnosis and can be used as the main examination method of diagnosis. Reports of children suffering from PMC are rare. Herein, we report a case of PMC in a child. This report has some clinical value for the study of the spectrum of PMC in patients.
Diarrhea is a fairly common problem among the elderly that has a higher morbidity and mortality compared with the general population. There are multiple reasons for diarrhea in the elderly that can be stratified by different mechanisms: infectious, osmotic, secretory, inflammatory, and malabsorptive. Oral hydration and dietary management are the basic management principles for all forms of diarrhea but specific treatment should address the root cause of diarrhea in order to improve outcomes.
Resumen
La infección por Clostridium difficile es la causa más frecuente de diarrea nosocomial y presenta un incremento en su incidencia con la edad. Las manifestaciones clínicas, la tasa de resistencia, el riesgo de recurrencia y la respuesta a los diferentes tratamientos es diferente en la población adulta joven comparado con la población mayor.
El objetivo de esta revisión es actualizar la epidemiología, patogenia, diagnóstico, tratamiento y prevención de la infección por C. difficile en este grupo de edad, con la evidencia que hay hasta el momento actual.
Despite lack of regulatory approval, fecal microbiota transplantation (FMT) is widely performed to manage C. difficile infection (CDI), particularly recurrent CDI. Herein, we critically review the available randomized controlled trials of FMT and address the following questions: Is FMT better than drug management of recurrent CDI?; Is FMT treatment per se or adjunctive treatment to antibiotics for CDI?; and, Is FMT safe? Finally, we elaborate non-FMT options for the management of recurrent CDI. Although promising, FMT should be reserved for patients who have failed appropriate antibiotic management of recurrent CDI.
Objective
To estimate the clinical and economic burden of Clostridium difficile -associated disease (CDAD) in Massachusetts over 2 years.
Design
A retrospective analysis of Massachusetts hospital discharge data from 1999-2003 was conducted. Cases of CDAD in 2000 were identified using code 008.45 from the International Classification of Diseases, Ninth Revision, Clinical Modification ; patients were excluded if they had a hospitalization in the prior year during which a diagnosis of CDAD was recorded. Hospitalizations for CDAD during 2001 and 2002 were examined. For primary case patients (ie, those for which CDAD was the principal diagnosis), all inpatient costs were deemed to be related, whereas for secondary case patients, all-patient refined diagnosis-related group assignment, case severity level, and length of stay (LOS) were used to calculate incremental costs attributable to CDAD. Costs were adjusted to the national level and reported in 2005 US dollars.
Results
The CDAD cohort consisted of 3,692 patients; 59% were women, and the mean age was 70 years. This group represented 1% of all patients hospitalized in Massachusetts in 2000 (96% of hospitals treated at least 1 case; range, 1-257 cases). Of patients who received a first hospital diagnosis of CDAD in 2000, a total of 28% were primary case patients; their mean LOS was 6.4 days, and the mean cost per stay was $10,212. For secondary case patients, the mean CDAD-related incremental LOS was 2.95 days, and the mean incremental cost per stay was $13,675 per patient. Of patients with CDAD who survived their index stay in 2000, a total of 455 (14%) had at least 1 readmission for CDAD within the subsequent 2 years (mean number of readmissions, 1.4 per patient; range, 1-7 readmissions), with a mean time to first readmission of 3 months. Over 2 years, a total of 55,380 inpatient-days and $51.2 million were consumed by CDAD management.
Conclusion
CDAD is widespread in Massachusetts hospitals. Rehospitalization with CDAD, if it occurs, generally happens within a few months and happens multiple times for some patients. Based on this study's findings, a conservative estimate of the annual US cost for CDAD management is $3.2 billion dollars.
Clostridium difficile is a Gram-positive, anaerobic, spore-forming bacillus that is spread indirectly via the fecal-oral route through spores. Disturbance of gut microbiota due to antibiotic therapy causes abnormal proliferation of Clostridium difficile and toxin production, leading to the development of Clostridium difficile infection. A new, hypervirulent strain of Clostridium difficile, NAP1/B1/027, has been implicated in Clostridium difficile outbreaks associated with increased morbidity and mortality since the early 2000s. In 2013, van Nood et al. reported that in patients with recurrent Clostridium difficile infection, fecal microbiota transplantation resulted in better treatment outcomes compared with conventional antibiotic treatment, which has attracted increased attention. Recently, monoclonal antibodies against toxin B, vaccines and a polystyrene binder of Clostridium difficile toxins have been developed for the treatment of Clostridium difficile infection. In this article, we will outline the epidemiology, pathophysiology, diagnosis and treatment of Clostridium difficile infection, and also describe the relationships between ulcerative colitis and Clostridium difficile infection.
Liver transplant recipients are considered to be at high risk for Clostridium difficile infection, with an incidence of 2.7-8.0%, which is three times higher than that among other patients. A case of a patient who suffered from pseudomembranous colitis five times after living donor liver transplantation is reported. A 60-year-old woman underwent splenectomy and living donor liver transplantation using the left lobe of her spouse for primary biliary cirrhosis. The patient made a satisfactory recovery, except for splenic vein thrombosis. She was discharged on postoperative day 36; however, she developed pseudomembranous colitis due to Clostridium difficile infection five times within 6 months after transplant and was treated with oral vancomycin each time. At the fifth recurrence of pseudomembranous colitis, the patient received vancomycin taper treatment, dietary counseling, and repeat instructions regarding hand hygiene and house cleaning. The patient recovered and is currently well without recurrence of Clostridium difficile infection 36 months after living donor liver transplantation.
Cancer patients frequently suffer from gastrointestinal complications. In this manuscript, we update our 2013 guideline on the diagnosis and management of gastrointestinal complications in adult cancer patients by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). An expert group was put together by the AGIHO to update the existing guideline. For each sub-topic, a literature search was performed in PubMed, Medline, and Cochrane databases, and strengths of recommendation and the quality of the published evidence for major therapeutic strategies were categorized using the 2015 European Society for Clinical Microbiology and Infectious Diseases (ESCMID) criteria. Final recommendations were approved by the AGIHO plenary conference. Recommendations were made with respect to non-infectious and infectious gastrointestinal complications. Strengths of recommendation and levels of evidence are presented. A multidisciplinary approach to the diagnosis and management of gastrointestinal complications in cancer patients is mandatory. Evidence-based recommendations are provided in this updated guideline.
Im Gegensatz zur Pathophysiologie ist die klinische Symptomatik der Erkrankung durch Clostridium difficile seit mindestens 15 Jahren gut bekannt, das therapeutische Vorgehen steht seither im Wesentlichen fest [Übersichten u.a. 2, 4, 6, 18, 36]. Dennoch scheint die Erkrankung im Bewußtsein der Ärzte noch nicht sicher verankert zu sein. Neben einer etwas unübersichtlichen Nomenklatur mag das an einem trotz aller Fortbildungsbemühungen mangelhaften Bekanntheitsgrad liegen. Insofern lohnt sich eine kurze Wiederholung der wichtigsten Tatsachen.
Background: Clostridium dijfficile-associated diarrhea (CDAD) has become very important due to the increase in its incidence, severity, recurrence and the associated economic burden. Having a national consensus guideline is essential to improve its management. Objective: To build a multidisciplinary and evidence-based consensus in prevention, diagnosis and treatment of CDAD. Methods: We convened a panel of experts in the field of infectious diseases, gastroenterology, evidence-based medicine and consensus methodology. The panel conducted a structured review of published literature in CDAD evaluating evidence levels and recommendation degree according to the methodology proposed by the GRADE working-group. A modified three-round Delphi technique was used to reach a consensus among the experts. Results: A group of 16 experts was established, 12 of them answered 18 clinically relevant questions. The levels of agreement achieved by the panel of 16 experts were 79% in the first round and 100% in the second and third round. The main consensus recommendations in prevention are: restricting the use of proton-pump inhibitors, primary prophylaxis with probiotics in antibiotics users, education of health personnel, isolation for patients hospitalized with CDAD, and cleaning the rooms exposed to C. difficile with products based in chlorine or hydrogen peroxide. In the diagnosis: use of biology molecular-based techniques is preferred and if not available, glutamate dehydrogenase-based algorithms may be recommended. With regard to treatment: the use of oral metronidazole in mild-moderate CDAD and oral vancomycin in severe CDAD are recommended. Treat the first recurrence with the same antibiotics according to severity. In the case of second and subsequent recurrences consider prolonged therapy with vancomycin, rifaximin or fecal microbiota transplant. Conclusion: The first Chilean consensus on prevention, diagnosis and treatment of CDAD is presented, which is a major step in improving national standards in the management of this disease.
Antibiotic induced diarrhea is a spectrum of diseases varying from asymptomatic colonization with Clostridium difficile to fulminant colitis. The most common expression of this disease complex is antibiotic induced diarrhea without colitis. This chapter will cover the clinical and epidemiological manifestations of pseudomembranous colitis with special attention to the critically ill patient. Other causes of antibiotic induced diarrhea will be reviewed briefly.
Clostridium difficile was thought to be nonpathogenic until 1978, when Bartlett et al. identified C. difficile as the source of cytotoxin in the stools of patients with pseudomembranous colitis, a disorder frequently associated with antimicrobial use C. difficile is responsible for both hospital-acquired and community-acquired diarrhea. Clostridium difficile is transmitted via the fecal-oral route, disruption of the gut flora, typically by antibiotics, allows C. difficile to proliferate, thus resulting in infection C. difficileexerts its pathogenic effect mainly through the production of two exotoxins, toxin A and B. Usually, exposure to both antimicrobials andtoxin-producing C. difficile strains is necessary for the development of CDI. Host factors may be as important. CDI has a wide range of manifestations, causing a self-limited mild diarrheal illness to a fulminant life-threatening colitis. The two main risk factors for CDI are antibioticexposure and age older than 65 but other factors shouldalso be considered like the use of laxatives, proton pump inhibitors or H2 histamine as gastric protection, chemotherapy, renal failure, gastrointestinal surgery, nasogastric tube, mechanical ventilation, prolonged hospital stay. The most widely used diagnostic test for the diagnosis of CDI is the enzyme immunoassay (EIA) for toxin A or toxins A and B. Other methods include:an antigen test that detects the mitochondrial enzyme glutamate dehydrogenase (GDH) within C. difficile, used for screening, stool culture, the cytotoxicity cell assay, another highly sensitive and specific method is polymerase chain reaction( PCR), sensitivity being higher than 90% and specificity of 100%. Colonoscopy and flexible sigmoidoscopyalso used in certain situations, abdominal X-ray is used in cases of ileus or toxic megacolon. For treatment different antibiotics are used: metronidazole, Vancomycin is recommended in severe cases, other treatment options include: Fidaxomicin, Nitazoxanide, rifaximin, Teicoplanin, tigecycline, bacitracin,andfusidic acid. Probiotics are found in fermented milk, yogurt, powders and capsules as lactobacillus, bifidobacteria and Saccharomyces boulardii. They act by inhibiting bacterial adhesion to the intestinal mucosa.There are case reports according to which the use of intravenous unspecific immunoglobulin will benefit patients in recurrence, but there is little data in the literature. While the effectiveness of immunoglobulins remains controversial, monoclonal antibodies directedagainst toxins A and B have been shown to be protective against further relapses when compared to placebo, leaving the door open for future research. Fecal transplants or fecal bacteriotherapy is very promising, with success rates greater than 90% in patients with recurrent infections. In this approach, the stool may be introduced by esophagogastroduodenoscopy, colonoscopy or enema [89].In patients with fulminant infection, early surgery is important. Surgery showed a benefit compared to medical therapy, especially in patients with serum lactate >5 mmol/L and/or leukocytosis ≥50 x109/L. Cl.difficile can cause different rare cases including: inflammatory bowel disease (IBD), pseudomembranous colitis (PMC) that lead to death of a 22-year-old female university student following clindamycin treatment for coverage of a tooth extraction due to a dental abscess, the emergence of multidrug-resistant C. difficile PCR ribotype 046 may be detrimental to anti-tuberculosis chemotherapy, a case of C. difficile bacteremia in a patient who had underwent loop ileostomy is reported, mycoticaneurysm causedby C. difficile is also reported, the use of fecal transplantation as a safe and highly effective treatment for recurrent Clostridium difficile infection is repoterd, Clostridium difficile Infection in Infants and Children is reported also, Clostridium difficile is reported to be the first identified autotrophic bacterial pathogen[104], and Clostridium difficile enteritis is also reported.
Clostridium difficile-associated diarrhea (CDAD) is a major cause of nosocomial and antibiotic-associated diarrhea, and it is the commonest recognized cause of pseudomembranous colitis. Despite the recognition of this pathogen since 1978 as the major cause of antibiotic-associated diarrhea, availability of treatment, and recognized infection control measures, CDAD has remained a persistent problem in most hospitals. Moreover, since 2002 renewed interest in this infection has been stimulated by epidemic outbreaks in hospitals in Canada, United States, United Kingdom, and the Netherlands secondary to a hypervirulent strain of C. difficile, associated with high recurrence and increased severity.
Although, a large body of literature exists on the pathogenesis, epidemiology, diagnostic methods, and management of CDAD, we still have no effective prevention and no optimal therapy for recurrences. The disease, is mostly a nuisance to healthy, young subjects, complicating antibiotic therapy, but can be a fatal disease in the elderly and high-risk population. It should be noted that despite our inability to conquer and prevent CDAD, there has been no new treatment on the market for this condition in the past 25 years.
Clostridium difficile carriage rates are increased in IBD patients. C. difficile diarrhea has increased in frequency throughout the world and recent C. difficile epidemics have been linked to a hypervirulent C. difficile strain resulting in greater severity of disease. Although most mild to moderate cases of C. difficile infections continue to respond to metronidazole or vancomycin, efractory and recurrent cases may require alternative therapies. Alternative antibiotics, toxin binders, probiotics and immunological therapies can be considered for treatment of acute and recurrent C. difficile infections in severe and refractory situations. Future approaches to the control of nosocomial C. difficile infection may involve active or passive immunization of at-risk individuals.
This chapter deals with clostridial infections that cause intestinal disease in humans and in which diarrhea is a major or significant feature of the clinical syndrome. In addition to the distinct disease syndromes, clostridia are often involved in polymicrobial infections of the gastrointestinal tract and present without specific features except for the occasional association of gas at the infected site. The production of hydrogen gas by clostridia and C. perfringens accounts for radiographic and pathologic findings associated with emphysematous cholecystitis and pneumatosis cystoides intestinalis. Clostridia cause distinct gastrointestinal syndromes in humans as a result of the action of specific toxins on the intestinal mucosa. Host factors predispose to different clinical syndromes and include: antimicrobial exposure, trypsin deficiency, and neutropenia. Clostridia are widely dispersed in the environment and the risk of developing a particular syndrome relate to the relative predominance of a particular species in that environment, such as in hospitals (C. difficile diarrhea) or the Highlands of Papua New Guinea (C. perfringens type C enteritis).. Ingestion of contaminated foods in the case of C. perfringens type A diarrhea and C. perfringens type C enteritis may also determine the type of syndrome displayed.
A 77-year-old female was referred because of abdominal pain and diarrhea, which occurred two days after antibiotic treatment (cefotiam, 2ｇ/day) . Because endoscopic examination showed multiple white plaques on the sigmoid colon and Clostridium difficile toxin was detected in colostrum, a diagnosis of pseudomembranous colitis was made. Although oral vancomycin (VCM) administration relieved the symptoms, fever and diarrhea recurred 11 days after the administration of VCM was terminated. Colonoscopy again revealed pseudomembranes as well as marked mucosal edema of the colon. Abdominal CT demonstrated double layers of the large bowels, being compatible with marked mucosal edema. Metronidazole (MTZ) was co-administered with VCM for 15 days and VCM was tapered in 22 days. The abdominal symptoms dissappeared and no abnomality was shown on endoscopic examination. Any relapse of pseudomembranous colitis was not observed after cessation of the treatment. Remarkable mucosal edema of the colon was rarely presented with pseudomembranous colitis and was supposed to be a finding related with VCM-resistancy of pseudomembranous colitis.
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