No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Treatment of antibiotic-associated pseudomembranous colitis with cholestyramine resin
Abstract
Pseudomembranous colitis (PMC) is an infrequent but serious complication of oral and intravenous antibiotic therapy. Twelve patients with antibiotic-associated PMC, documented by sigmoidoscopy and rectal biopsy, were treated with cholestyramine resin. The mean time from the institution of therapy to cessation of diarrhea was 2.1 days. The response interval bore no relationship to the time symptoms were present prior to therapy. Complete resolution of sigmoidoscopic and histologic evidence of PMC usually accompanied or followed cessation of diarrhea. Obstipation was reported in 5 of 12 patients as a side effect of cholestyramine treatment. Therapy should be continued for up to five days after cessation of diarrhea to prevent recurrence of active PMC. Cholestyramine resin is shown to be an effective treatment for antibiotic-associated PMC.
... In addition, fulminant colitis is poorly responsive to antibiotic treatment [57]. Accordingly, toxin binding by monoclonal antibodies [58] or by anion [20,21] and cation exchange resins [25] have been explored as an adjunct or as an alternative. Recurrences are thought to arise from newly ingested spores and from persistent dysbiosis: the alterations in the gut microbiome, which promote the emergence of CDAD, require several weeks for their correction [3,23]. ...
Clostridioides difficile (C . difficile) infection is a major public health problem worldwide. The current treatment of C . difficile -associated diarrhea relies on the use of antibacterial agents. However, recurrences are frequent. The main virulence factors of C . difficile are two secreted cytotoxic proteins toxin A and toxin B. Alternative research exploring toxin binding by resins found a reduced rate of recurrence by administration of tolevamer. Hence, binding of exotoxins may be useful in preventing a relapse provided that the adsorbent is innocuous. Here, we examined the toxin binding capacity of G-PUR®, a purified version of natural clinoptilolite-tuff. Our observations showed that the purified clinoptilolite-tuff adsorbed clinically relevant amounts of C . difficile toxins A and B in vitro and neutralized their action in a Caco-2 intestinal model. This conclusion is based on four independent sets of findings: G-PUR® abrogated toxin-induced (i) RAC1 glucosylation, (ii) redistribution of occludin, (iii) rarefaction of the brush border as visualized by scanning electron microscopy and (iv) breakdown of the epithelial barrier recorded by transepithelial electrical resistance monitoring. Finally, we confirmed that the epithelial monolayer tolerated G-PUR® over a wide range of particle densities. Our findings justify the further exploration of purified clinoptilolite-tuff as a safe agent in the treatment and/or prevention of C . difficile -associated diarrhea.
... CDI is a toxinmediated disease, and thus neutralizing the toxins would seem to be an effective way of treating it without altering bowel flora. The anion-binding resins colestipol and cholestyramine have not be found to be effective in primary therapy for CDI, however, they are beneficial as adjunctive therapy for relapsing infection [71]. Tolevamer is a non-absorbable anionic polymer that sequesters toxin A and toxin B [72]. ...
Clostridium difficile (C. difficile) infection (CDI) is the most common cause of -healthcare-associated infections in US hospitals. The epidemic strain NAP1/BI/ribotype 027 accounts for outbreaks worldwide, with increasing mortality and severity. CDI is acquired from an endogenous source or from spores in the environment, most easily acquired during the hospital stay. The use of antimicrobials disrupts the intestinal microflora enabling C. difficile to proliferate in the colon and produce toxins. Clinical diagnosis in symptomatic patients requires toxin detection from stool specimens and rarely in combination with stool culture to increase sensitivity. However, stool culture is essential for epidemiological studies. Oral metronidazole is the recommended therapy for milder cases of CDI and oral vancomycin or fidaxomicin for more severe cases. Treatment of first recurrence involves the use of the same therapy used in the initial CDI. In the event of a second recurrence oral vancomycin often given in a tapered dose or intermittently, or fidaxomicin may be used. Fecal transplantation is playing an immense role in therapy of recurrent CDI with remarkable results. Fulminant colitis and toxic megacolon warrant surgical intervention. Novel approaches including new antibiotics and immunotherapy against CDI or its toxins appear to be of potential value.
... Not all alternative therapies have shown clinical benefit. Anion-binding resins, which could bind toxins without disturbing the microbiome [45], have not been shown to be effective as primary therapy for CDI [24,46,47], although they may be beneficial as adjunctive therapy in relapsing infection [48]. There are case reports describing the treatment of severe or recurrent CDI with intravenous immunoglobulin that contains C. difficile antitoxin. ...
The most important infectious cause of antibiotic-associated diarrhoea and colitis is Clostridium difficile, which is a Gram-positive, anaerobic, spore-forming, toxin-producing bacillus. In this overview we will discuss the diagnostic and therapeutic management of patients presenting with suspected or proven C. difficile infection (CDI). The clinical spectrum varies from asymptomatic C. difficile carriers to fulminant colitis with multi-organ failure. The onset of symptoms is usually within 2 weeks after initiation of antibiotic treatment. Diagnosis is based on the combination of clinical symptoms and either a positive stool test for C. difficile toxins or endoscopic or histological findings of pseudomembranous colitis. There is no indication for treatment of asymptomatic carriers, but patients with proven CDI should be treated. Treatment consists of cessation of the provoking antibiotic treatment, secondary prevention by infection control strategies, and treatment with metronidazole or vancomycin. Treatment of recurring CDI, severe infection, the need for surgery, and novel alternative potential treatment strategies will be discussed. The concurrent increase in multiresistant colonisation and increasing numbers of asymptomatic carriers of C. difficile will lead to an increase of the situation in which patients with severe infections, treated with broad-spectrum antibiotics, will develop concurrent severe CDI. We will discuss possible therapy strategies for these patients.
... Anion exchange resins have been given to patients with pseudomembranous colitis with variable response. [42][43][44] In RCDAD, colestipol was given in combination with tapering doses of vancomycin to 11 patients, with resolution of symptoms and no recurrence for at least 6 weeks. 45 Because these agents can also bind antimicrobials, they should not be given within 2-3 hours of antibiotic ingestion. ...
Treatment of recurrent Clostridium difficile-associated diarrhea can be challenging. Once patients develop recurrent disease, further episodes are common and can continue for months or even a year or more. Treatment begins with a repeat standard 10-day course of antibiotics, followed by tapering and/or pulsing of the antibiotic dose. Probiotics can also be useful, particularly the nonpathogenic yeast Saccharomyces boulardii. Stool reconstitution via fecal enemas, colonoscopy, and nasogastric tubes have, been performed to restore normal colonic flora. Additional approaches under investigation, such as vaccination against C. difficile, show encouraging preliminary results.
... Anion binding resins, like cholestyramine and colestipol, have been used to treat CDI. The non-absorbable resin binds to C. difficile toxin removing 99% of the cytotoxic activity [169] . However; concerns have been raised about the use of these toxin-binding agents, because they also bind to vancomycin [170] . ...
Clostridium difficile infection (CDI) presents a rapidly evolving challenge in the battle against hospital-acquired infections. Recent advances in CDI diagnosis and management include rapid changes in diagnostic approach with the introduction of newer tests, such as detection of glutamate dehydrogenase in stool and polymerase chain reaction to detect the gene for toxin production, which will soon revolutionize the diagnostic approach to CDI. New medications and multiple medical society guidelines have introduced changing concepts in the definitions of severity of CDI and the choice of therapeutic agents, while rapid expansion of data on the efficacy of fecal microbiota transplantation heralds a revolutionary change in the management of patients suffering multiple relapses of CDI. Through a comprehensive review of current medical literature, this article aims to offer an intensive review of the current state of CDI diagnosis, discuss the strengths and limitations of available laboratory tests, compare both current and future treatments options and offer recommendations for best practice strategies.
... The use of resins to bind unwanted compounds either in vivo or in vitro has found applications both in the laboratory (e.g., ion exchange chromatography) and to a lesser extent in clinical therapeutics. 8 The first application of this principle to blood culture methods was the Antimicrobial Removal Device (ARD®, Marion Scientific, Kansas City, MO) which was designed to bind antimicrobials present in blood and thus enhance recovery of organisms. 914 Evaluations of the ARD have produced somewhat controversial results, ranging from no advantage being observed over conventional processing 1217 to significantly greater numbers of pathogens being recovered by the ARD processed samples. 2 -4 Because of the considerable amount of manipulation necessary in processing samples collected in ARD vials and the need to enter these vials at the time of inoculation into broth, there has been some concern regarding the likelihood of introducing contaminating organisms and the feasibility of ...
A new blood culture medium (16B) containing adsorbent and cationic exchange resins has become available for use with the BACTEC instrument (Johnston Laboratories, Towson, MD). Its purpose is to enhance the detection of bacteremia through binding of antimicrobials. The performance of the BACTEC 16B resin medium was compared with the routine BACTEC 6B medium in patients with suspected sepsis receiving antibiotics. A total of 1,227 blood specimens were inoculated in 6B and 16B media and yielded 93 positive cultures from 43 clinically septic patients. Of 103 bacterial isolates recovered, 63 (61.2%) were recovered in both media, 14 (13.6%) in the routine 6B medium only, and 26 (25.2%) in the resin medium only (P greater than 0.05). Staphylococci, both coagulase positive and negative, were recovered much more frequently in resin medium (P less than 0.01). When the results of all the blood culture sets collected for each patient on any given day were considered, the routine 6B medium was the only source of isolation for seven bacterial species in six patients, and the resin medium was the only source of isolation for nine species in nine patients. However, of the nine organisms whose sole isolation source was the resin medium, eight were recovered early in the course of antibiotic therapy (6 within 24 to 36 hours and 2 within 36 to 48 hours of the first antibiotic dose) and had been isolated previously in routine 6B medium. In no instance was the antibiotic regimen changed as a result of the persistence of the organism in resin medium in the early phases of treatment. The use of resin medium did not improve overall detection time for 63 isolates recovered in both media. In conclusion, although the 16B resin medium did recover a greater number of bacterial isolates, it contributed very little information that might be of use in modifying and improving the treatment of septic patients receiving antimicrobials.
... Nitazoxanide, a new anti-parasitic/anti-bacterial agent (Musher et al., 2006, Musher et al., 2007a, ramoplanin (Freeman et al., 2005) and teicoplanin (Nelson, 2007) also show promise. Toxin binders (e.g., cholestyramine (Sinatra et al., 1976, Kreutzer & Milligan, 1978) have been used in uncontrolled studies. Telovamer, a toxin-binding resin, showed promise in in vitro (Hinkson et al., 2008), animal models (Hinkson et al., 2008) and early human studies (Louie et al., 2006), but more recent studies in humans have been less promising (Weiss, 2009). ...
Clostridium difficile is a well recognized pathogen of humans and animals. Although C. difficile was first identified over 70 years ago, much remains unknown in regards to the primary source of human acquisition and its pathobiology. These deficits in our knowledge have been intensified by dramatic increases in both the frequency and severity of disease in humans over the last decade. The changes in C. difficile epidemiology might be due to the emergence of a hypervirulent stain of C. difficile, ageing of the population, altered risk of developing infection with newer medications, and/or increased exposure to C. difficile outside of hospitals. In recent years, there have been numerous reports documenting C. difficile contamination of various foods, and reports of similarities between strains that infect animals and strains that infect humans as well. The purposes of this review are to highlight the many challenges to diagnosing, treating, and preventing C. difficile infection in humans, and to stress that collaboration between human and veterinary researchers is needed to control this pathogen.
... Both cholestyramine and colestipol have been used alone or as adjuvants to antibiotics to treat CDI, but their efficacy is poor. 63 A novel toxin-binding resin (tolevamer) was tested recently for treatment of CDI but was less effective than either metronidazole or vancomycin. 40 Individuals with recurrent CDI lack protective immunity to C difficile toxins. ...
Clostridium difficile infection (CDI) is a common and increasingly severe nosocomial infectious disease. The case of Mr S, a 76-year-old man with multiple recurrences of CDI, illustrates the difficulties in treating recurrent disease and the way it complicates the management of other medical conditions. Risk factors for CDI include antimicrobial use, hospital admission, advancing age, and severe underlying disease. A clinical diagnosis of CDI is usually confirmed by identifying C. difficile toxins in a stool sample. Evidence supports metronidazole, 500 mg every 6 hours for 10 to 14 days, as the treatment of choice for mild to moderately severe CDI. Oral vancomycin, 125 mg every 6 hours for 10 to 14 days, is recommended for severe CDI, for which it is more effective than metronidazole. Recurrent CDI occurs in more than 20% of patients when metronidazole or vancomycin treatment is discontinued. Few studies have evaluated treatment options for recurrent CDI, but a prolonged, tapering, and pulse-dosed regimen of oral vancomycin is commonly used. Careful attention to antimicrobial stewardship and infection control practices is essential to curb this nosocomial, iatrogenic disease.
... The resin binds the toxins produced by the organism and minimizes the tissue damage which occurs during the disease. The alleviation of the symptoms, however, is more variable compared with the use of antibiotics, and some patients do not respond at all to this type of treatment (117,228). ...
Clostridium difficile is the etiologic agent of pseudomembranous colitis, a severe, sometimes fatal disease that occurs in adults undergoing antimicrobial therapy. The disease, ironically, has been most effectively treated with antibiotics, although some of the newer methods of treatment such as the replacement of the bowel flora may prove more beneficial for patients who continue to relapse with pseudomembranous colitis. The organism produces two potent exotoxins designated toxin A and toxin B. Toxin A is an enterotoxin believed to be responsible for the diarrhea and mucosal tissue damage which occur during the disease. Toxin B is an extremely potent cytotoxin, but its role in the disease has not been as well studied. There appears to be a cascade of events which result in the expression of the activity of these toxins, and these events, ranging from the recognition of a trisaccharide receptor by toxin A to the synergistic action of the toxins and their possible dissemination in the body, are discussed in this review. The advantages and disadvantages of the various assays, including tissue culture assay, enzyme immunoassay, and latex agglutination, currently used in the clinical diagnosis of the disease also are discussed.
Dehydration caused by diarrhea remains a major source of morbidity and mortality worldwide. Dehydration is a common clinical presentation seen by most physicians. Clinical diagnosis depends on the recognition of signs and symptoms as well as change in weight. Laboratory studies are helpful in categorizing the dehydration as isotonic, hyponatremic, or hypernatremic, which is necessary to plan appropriate therapy. In many situations, oral rehydration therapy is possible and desirable. Intravenous rehydration remains the standard of care for children with severe dehydration and shock.
Clostridium difficile was first identified in 1978 as a diarrhea-causing bacterium in humans. In the last three decades, C. difficile infection (CDI) has reached an epidemic state, both in health care and community settings worldwide. There has been substantial progress in the field of CDI, including identification of novel risk factors, presence of CDI in individuals not considered at risk previously, and treatment options including new drugs, monoclonal antibodies, and fecal microbiota transplantation. This review discusses epidemiology, novel and traditional risk factors, and updates in management for CDI.
Clostridium difficile infection (CDI) is a major cause of nosocomial diarrhea with the potential for significant morbidity and mortality. Colonization in a susceptible individual, with risk factors such as prior antibiotic use, advanced age, or medical comorbidities, may result in symptomatic infection. Although patients with a gynecologic malignancy may be at a higher risk of developing CDI due to an increased likelihood of having one or more risk factors, data do not consistently support the idea that chemotherapy or cancer itself are independently associated with CDI. For diagnosis of CDI, we recommended using a multi-step approach, with a highly sensitive initial rapid test such as the enzyme immunoassay (EIA) for glutamate dehydrogenase (GDH) or nucleic acid amplification testing (NAAT), followed by confirmatory testing with of the above two tests or EIA toxin A/B, which has high specificity. Treatment varies based on the severity of disease. We recommend vancomycin as first-line therapy for an initial episode of mild/moderate or severe CDI, with consideration of fidaxomicin for patients at particularly high risk for recurrence. Rectal vancomycin may play an adjunctive role for some severe cases, while surgical intervention is indicated for fulminant CDI if no improvement six or more days after initiating medical therapy. For non-severe recurrent disease, the initial treatment regimen should be repeated, while subsequent episodes are more appropriately treated with a tapered and pulsed dose of vancomycin, fidaxomicin, or fecal microbiota transplantation.
Pseudomembranöse Colitis (PMC) ist eine morphologische Diagnose. Siebesagt, daß an der Dickdarmschleimhaut eine Entzündung abläuft, die durch pilzförmige, manchmal konfluierende Auflagerungen von Fibrin, Graunulocyten, Schleim und abgestoßenem Zellmaterial auf zunächst umschriebenen Schleimhautnekrosen charakterisiert ist. Die Veränderungen können durch unterschiedliche Noxen hervorgerufen werden, sind also ätiologisch nicht spezifisch. Am häufigsten kommen sie heutzutage im Rahmen einer antibioticaassoziierten Colitis vor, die — wie man seit 5 Jahren weiß — durch ein Toxin von Clostridium diffìcile bedingt ist. Um zu betonen, daß PMC und antibioticaassoziierte Cohtis a priori nicht gleichzusetzen sind, soll auf letztere in Abschn. 5 getrennt eingegangen werden.
The bile acid-binding resins cholestyramine (CH) and colestipol (CO) are effective drugs for the treatment of patients with elevated low-density lipoprotein (LDL) cholesterol plasma concentrations without concurrent hypertriglyceridemia. Since the bile acid sequestrants are not absorbed in the gastrointestinal tract, they cannot cause direct systemic side effects. They activate the natural pathway for LDL elimination from the circulation by stimulating the expression of LDL receptors. Thus, the sequestrants are ideal drugs for treatment of LDL hypercholesterolemia from the pharmacologist’s point of view. However, their mode of administration as a bulky powder and the gastrointestinal side effects may cause practical problems.
» Die Pflege eines Sterbenden muss zuallererst seine physischen Bedürfnisse berücksichtigen (Kübler-Roos 2000) «
• Objective: To report recent changes in the epidemiology of Clostridium difficile-associated diarrhea (CDAD) and to discuss its diagnosis, treatment, and prevention. • Methods: Qualitative review of the literature. • Results: CDAD continues to be a major problem in the health care setting. A new virulent strain of C. difficile has been associated with several notable hospital outbreaks. This strain, called BI/NAP1, produces 16 to 23 times the amount of toxin A and B produced by standard strains and has been associated with more severe CDAD and increased mortality. In addition to previously identified predisposing factors, risk factors for CDAD associated with this new strain include age > 65 years and fluoroquinolone use. For initial treatment of mild to moderate CDAD, metronidazole is still recommended; however, vancomycin is now recommended as initial therapy in moderate to severe disease. Studies of new drugs for treatment of CDAD are currently in process. Recurrent diarrhea remains a frequent complication of CDAD, but studies are necessary to define the best approach for treatment of recurrent disease. • Conclusion: A new strain of C. difficile has emerged that causes more severe disease and treatment failures with standard therapies. New, more effective treatment options are urgently needed.
There has been a significant increase in the incidence and severity of Clostridium difficile-associated diarrhea (CDAD) in the past several years, including outbreaks in multiple states and provinces in the United States and Canada, as well as in the United Kingdom. A new, highly virulent strain of C. difficile has appeared that is less responsive to standard therapy and associated with a high rate of recurrence. Along with nosocomially acquired infections there has been a rise in the number of community-acquired cases of CDAD, even among those without prior antibiotic exposure. Many factors have contributed to this epidemic, including the development of resistance to the widely used fluoroquinolones class of antibiotics. Because this new strain is less responsive to standard therapy, particularly metronidazole, a number of new antibiotics and other therapies are actively being investigated for use in both primary and recurrent CDAD. A multifaceted approach to managing CDAD is called for, including active surveillance, antibiotic stewardship, and meticulous attention to contact precautions, including gloves, gowns, and hand washing.
Clostridium difficile-associated diarrhea (CDAB) has become the most common cause of infectious diarrhea acquired in the hospital, with an estimated 3 million annual cases and an annual cost of $1 billion. Risk factors for CDAD include antibiotic use (especially ampicillin, clindamycin, and cephalosporins), advanced age, and gastrointestinal surgery. Specific diagnosis of CDAD is made with an enzyme immunoassay to detect toxins A and B. Metronidazole remains the initial treatment of choice, with a 95% success rate. Vancomycin is reserved for failures. Despite the high initial success rates, recurrence of CDAD remains a significant problem in 20% to 30% of cases, with increased cost and substantial morbidity. Efforts to prevent CDAD will need to be strengthened, including education and better compliance with isolation, use of gloves, and hand washing.
Clostridium difficile infection (CDI) is increasingly prevalent, dangerous and challenging to prevent and manage. Despite intense national and international attention the incidence of primary and of recurrent CDI (PCDI and RCDI, respectively) have risen rapidly throughout the past decade. Of major concern is the increase in cases of RCDI resulting in substantial morbidity, morality and economic burden. RCDI management remains challenging as there is no uniformly effective therapy, no firm consensus on optimal treatment, and reliable data regarding RCDI-specific treatment options is scant. Novel therapeutic strategies are critically needed to rapidly, accurately, and effectively identify and treat patients with, or at-risk for, RCDI. In this review we consider the factors implicated in the epidemiology, pathogenesis and clinical presentation of RCDI, evaluate current management options for RCDI and explore novel and emerging therapies.
Copyright © 2015. Published by Elsevier Ltd.
To systematically search the literature for trials evaluating luminal toxin-binding agents (LTBAs) for Clostridium difficile infection (CDI).
A systematic search was conducted utilizing PubMed and International Pharmaceutical Abstracts with the following terms: anion-exchange resins, C difficile, cholestyramine, tolevamer, and colestipol. Articles were included if published in the English language and reported clinical outcomes of more than 5 adult humans with CDI treated with LTBAs.
Nearly all clinical trials evaluated LTBA as monotherapy for CDI and LTBAs are inferior to standard therapy. In contemporary practice, LTBAs are employed as adjunctive or sequential therapy for which there is a paucity of data. Some data suggest potential efficacy for recurrent CDI. Current guidelines for CDI assert LTBAs are contraindicated due to drug-drug interactions with vancomycin. However, the impact of this interaction on clinical outcomes has not been evaluated, and it is unknown whether higher doses of vancomycin or separating the administration of LTBAs from vancomycin would mitigate this interaction.
LTBA monotherapy is inferior to vancomycin and metronidazole for CDI. Some data indicate possible benefit in reducing recurrent CDI, but outcomes with adjunctive and/or sequential LTBAs are unavailable. Further studies are needed to investigate the role of LTBAs for CDI.
© The Author(s) 2015.
„Die Pflege eines Sterbenden muss zuallererst seine physischen Bedürfnisse Berücksichtigen“. (Kübler-Ross 2000)
Thirty-eight patients with severe antibiotic-associated postoperative diarrhoea were entered into a randomized controlled trial to compare colestipol (an ion exchange resin) in 17 patients with placebo (sherbet) in 21 patients. Clostridium difficile or its toxin was present before treatment in 12 of the colestipol group, compared with only 5 in the placebo group. Because of the low incidence of Cl. difficile or its toxin, the placebo group data from 22 patients receiving placebo in a previous trial (9 of whom had Cl. difficile or toxin) were included for comparison. Neither colestipol nor placebo had any influence on the faecal excretion of Cl. difficile or its toxin. Colestipol was clinically no better than placebo. In view of the persistent faecal excretion of Cl. difficile toxin, ion exchange resins cannot be recommended for the treatment of antibiotic-associated colitis.
We have reviewed 66 cases of antibiotic-associated colitis since March 1975, which have been associated with a 27 per cent mortality. We believe antibiotics may predispose patients to this condition which is caused by a toxin produced by Clostridium difficile. Although the disease is rare, it is more common than previously reported. The presentation, methods of diagnosis and treatment are discussed.
During the 5 years 1985–1989, 24 (32%) of 76 patients treated for Hirschsprung's disease (HD) developed enterocolitis, this being present at the time of diagnosis in 10 (13%) infants, 7 of whom were neonates. HD presented as necrotizing enterocolitis in 5 neonates, 4 of whom were premature. The enterocolitis developed postoperatively in 14 (18%) patients, in 7 after an enterostomy and in 7 after a pull-through procedure. Recurrent episodes of enterocolitis occurred in 4 of the patients who developed postoperative enterocolitis. The risk of enterocolitis was increased in girls, in patients with associated Down's syndrome, those with a family history of HD, and those managed by an endorectal pull-through procedure. The Duhamel procedure was associated with a low (5%) incidence of postoperative enterocolitis. Long-segment aganglionosis was not associated with an increased risk of enterocolitis and preoperative enterocolitis conferred no increased risk of postoperative enterocolitis.
Viele Antibiotika, besonders Lincomycine, knnen Durchflle mit und ohne Enterocolitis hervorrufen. Die Pathogenese der Diarrhoen ohne Colitis ist ungeklrt; eine kolloidosmotische Wasserbindung im Colon durch bakteriell nicht abgebaute endogene Glykoproteine wird erwogen. Die Ursache der Enterocolitis ist seit zwei Jahren bekannt. Zugrunde liegt eine Proliferation toxinbildender Clostridien im Lumen, erwiesen fr Cl. difficile. Verbesserte Nachweismethoden fr Toxin und Erreger befinden sich in der Entwicklung. Endoskopisch sind Pseudomembranen charakteristisch, aber nicht antibiotika-spezifisch, sie knnen fehlen oder der Diagnostik entgehen. Die Inzidenz der Enterocolitis ist auffllig wechselnd, eine Rolle asymptomatischer Clostridientrger mglich. Der potentiell tdliche Verlauf erfordert eine rasche Diagnostik und Therapie, mit Absetzen des Antibiotikums, intensiven untersttzenden Manahmen und zumindest in schweren Fllen oralem Vancomycin.Many antibiotics, particularly the lincomycins, may cause diarrhoea with or without enterocolitis. The pathogenesis of antibiotic-associated diarrhoea without colitis is uncertain; colloidosmotic water binding in the colon by endogenous glycoproteins undegraded by colonic bacteria is considered. Antibiotic-associated enterocolitis is now known to be due to toxin-producing clostridia, proven for Cl. difficile. Improved methods for the detection of toxin and clostridia are presently being studied. Endoscopically, pseudomembranes are characteristic but not antibiotic-specific, they may be absent or missed diagnostically. A possible role of asymptomatic clostridiacarriers in enterocolitis clustering remains to be determined. The potentially lethal course of the disease requires rapid diagnosis and therapy, with discontinuation of the antibiotic, intensive supportive measures and, at least in severe disease, oral vancomycin.
Clostridium difficile is a spore-forming, toxin-producing, anaerobic bacterium abundant in soils and water. Frequent and early colonization of the human intestinal flora is common and often asymptomatic. Antimicrobials given commonly disrupt the intestinal microflora and through proliferation in colon and production of toxin A and B it precipitates C. difficile infection (CDI). The enterocytic detachment and bowel inflammation provoke C. difficile-associated diarrhoea (CDAD) sometimes developing into severe pseudomembranous colitis (PMC) and paralytic ileus. Infection is acquired from an endogenous source or from spores in the environment, most easily facilitated during hospital stay. In the elderly, comorbidity, hospitalization and antimicrobial treatment present as major risk factors and the slow recolonization of the normal flora likely responsible for single or multiple recurrences of CDI (25-50%) post therapy. The key procedure for diagnosis is toxin detection from stool specimens and sometimes in combination with culture to increase sensitivity. In mild cases stopping the offending antimicrobial will lead to resolution (25%) but standard therapy still consist of either oral metronidazole or vancomycin. Alternative agents are presently being developed and fidaxomicin, as well as nitrothiazolide are promising. Furthermore, host factors like low antitoxin A levels in serum relates to increased risk of recurrence and small numbers of patients have received immunoglobulin with good results. An immunogenic toxoid vaccine has been developed and human colostrum rich in specific secretory Ig A also support the future use of immunotherapy. Today we experience a tenfold increase of CDI incidence in the western world and both epidemics and therapeutic failure of metronidazole is contributing to morbidity and mortality. The current epidemic of the C. difficile strain NAP1/027 emerging in 2002 in Canada and the USA has now spread to most parts of Europe and virulence factors like high toxin production and sporulation challenge the therapeutic situation and cause great concern among infection control workers. Excessive use of modern fluoroquinolones is thought to play an important role in facilitating this epidemic since NAP1/027 was shown to have acquired moxifloxacin resistance compared to historical strains of the same genotype. Both the current epidemic like this and other local outbreaks from resistant or virulent strains warrant culture to be routinely performed enabling susceptibility testing and typing of the pathogen. Genotyping is most commonly done today by pulse-field gel electrophoresis (PFGE) or PCR ribotyping but multilocus variable-number tandem-repeat analysis (MLVA) seems promising. Epidemiological surveillance using all these tools will help us to better understand the global spread of C. difficile.
Clostridium difficile infection is an increasing burden to the health care system, totaling more than $1 billion/year in the United States. Treatment of patients with C difficile infection with metronidazole or vancomycin reduces morbidity and mortality, although the number of patients that do not respond to metronidazole is increasing. Despite initial response rates of greater than 90%, 15%-30% of patients have a relapse in symptoms after successful initial therapy, usually in the first few weeks after treatment is discontinued. Failure to develop specific antibody response has recently been identified as a critical factor in recurrence. The review discusses the different management strategies for initial and recurrent symptomatic C difficile infections.
Vancomycin given by mouth is effective for the treatment of pseudomembranous colitis, a disease now known to be caused by an exotoxin of Clostridium difficile. Only one relapse of colitis after treatment with vancomycin has been reported. This report documents the relapse of colitis in three patients after discontinuation of treatment with vancomycin by mouth.
Recent evidence indicates that toxigenic Clostridium difficile strains are a major cause of antimicrobial-associated ileocecitis in laboratory animals and pseudomembranous colitis in humans. C. difficile ATCC 9689 was cultivated in a synthetic medium to which 3% ultrafiltrated proteose peptone was added. Purification of the toxin from broth filtrate was accomplished through ultrafiltration (100,000 nominal-molecular-weight-limit membrane), precipitation with 75% (NH4)2SO4, and chromatographic separation using Bio-Gel A 5m followed by ion-exchange chromatography on a diethylaminoethyl-Sephadex A-25 column. The purified toxin displayed only one band on polyacrylamide gel electrophoresis, and approximately 170 pg was cytopathic for human amnion cells. The isolated toxin was neutralized by Clostridium sordelli antitoxin, heat labile (56 degrees C for 30 min), and inactivated at pH 4 and 9; it had an isoelectric point of 5.0, increased vascular permeability in rabbits, and caused ileocecitis in hamsters when injected intracecally. Treatment of the toxin with trypsin, chymotrypsin, pronase, amylase, or ethylmercurithiosalicylate caused inactivation, whereas lipase had no effect. By gel filtration, its molecular weight was estimated as 530,000. Upon reduction and denaturation, the toxin dissociated into 185,000- and 50,000-molecular-weight components, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Extensive dissociation yielded only the 50,000-molecular-weight component. The toxin appears to be protoplasmic and is released into the surrounding environment upon autolysis of the cells. Attempts to correlate specific enzymatic activity with the toxin have been unsuccessful. These studies will help delineate the role of C. difficile toxin in antimicrobial-associated colitis and diarrhea.
Among 56 cases who presented to Kanto-Teishin Hospital complaining of bloody diarrhea or considerable hematochezia of acute onset, 8 cases (14.3%) were considered due to colitis associated with oral ampicillin therapy. The bloody diarrhea, often with abdominal cramps, began 2-7 days after starting the treatment. The dosage of ampicillin taken ranged from 2.0 to 4.5 g. Early total colonoscopy and biopsy revealed marked mucosal hemorrhage with minimal or no inflammatory changes mainly in the right colon. Rectum and sigmoid colon are completely normal except in one case. Symptoms rapidly resolved after the endoscopy. At follow-up colonoscopy, performed 4-12 days later, the mucosal changes had cleared completely. There was no evidence to support a hypersensitivity reaction of the colonic mucosa to ampicillin. We believe that right-sided hemorrhagic colitis is one of the common forms of colitis associated with ampicillin. Its differentiation from other kinds of acute colitis and the importance of early total colonoscopy are discussed.
Clostridium difficile infection is a common and potentially lethal complication of antibiotic usage. Since the aetiology of antibiotic-associated colitis was discovered 14 years ago, two antibiotics in particular, metronidazole and vancomycin, have been used to treat C. difficile infection. Studies comparing the efficacy of these antibiotics are reviewed. It is now apparent that many of the so-called 'relapses' of C. difficile infection following antibiotic treatment are, in fact, re-infections. Such findings have major infection control implications.
With the increased use of prophylactic and broad-spectrum antibiotics, pseudomembranous colitis has emerged as a significant clinical problem. Management with specific anti-Clostridium difficile therapy (vancomycin or metronidazole) has reduced mortality to less than 2%. Nevertheless, the disease may progress to a fulminant toxic colitis or colonic perforation. Additionally, another subset of patients will present with a dramatic clinical picture, suggesting acute peritonitis, eventuating in unnecessary laparotomy. This report reviews both the medical and surgical literature during the past 15 years of patients treated for pseudomembranous colitis. Analysis of this clinical data has provided us with the opportunity to both define the role of surgery in this disorder and illustrate the necessity for a combined medical and surgical cooperative approach in the early management of this iatrogenic disease.
To assess the effectiveness of screening by faecal occult blood tests, 107,349 people without symptoms of colorectal disease identified from general practitioner records have been randomly allocated to test and control groups. 53,464 test subjects were invited to carry out the screening test; 27,651 (53%) of the 52,258 who received the tests did so. Further investigation of the 618 (2.3%) with positive tests showed 63 cancers (52% stage A) and 367 adenomas (266 subjects). Rescreening of subjects with negative results every 2 years (9510 first rescreen, 3639 second) has shown a significant fall in the rate of positive results (1.7% of 7344; 0.3% of 2906). Cancers have also been diagnosed in 20 subjects presenting in the interval between a negative test and rescreening, and in 83 non-responders. The incidence of cancer in the control group (123 subjects; 10.6% stage A) was 0.72 per 1000 person-years. Cancers detected by screening were at a less advanced pathological stage, but it is too early to show any effect of screening on mortality from colorectal cancer.
Six patients with chronic relapsing diarrhoea caused by Clostridium difficile were treated with rectal instillation of homologous faeces (one patient) or a mixture of ten different facultatively aerobic and anaerobic bacteria diluted in sterile saline (five patients). The mixture led to a prompt loss of Cl difficile and its toxin from the stools and to bowel colonisation by Bacteroides sp, which had not been present in pre-treatment stool samples. Strains of Escherichia coli, Cl bifermentans, and Peptostreptococcus productus in the mixture inhibited the in-vitro growth of Cl difficile, which in turn inhibited the growth of Bacteroides ovatus, Bacteroides vulgatus, and Bacteroides thetaiotaomicron. The finding that Bacteroides sp had been absent during the patients' illness but was present after recovery suggests that the absence of Bacteroides sp may result in chronic relapsing Cl difficile diarrhoea, and that its presence may prevent colonisation by Cl difficile.
Diarrheal diseases remain a leading cause of morbidity and mortality in the developing countries and represent at least a nuisance in the industrialized world. Fluid and electrolyte replacement, particularly via oral rehydration, is the mainstay of therapy for the prevention and treatment of dehydration associated with these illnesses. Antibiotics are not indicated for the majority of enteric infections, and their promiscuous use can contribute to the escalating prevalence of bacterial resistance worldwide. Used judiciously, however, antimicrobial agents can ameliorate illness or curtail pathogen excretion and spread of disease, or both, in some diarrheal infections. Antimicrobial agents are indicated for shigellosis, cholera, traveler's diarrhea, amebiasis, and giardiasis. They are indicated in some specific circumstances to treat infections caused by Campylobacter, some categories of diarrheagenic E. coli, C. difficile, nontyphoidal Salmonella, and certain Vibrionaceae. Few adjunctive treatments provide proven benefit without risk of adverse reactions; most offer no advantage over placebo, and their general use is not encouraged.
Cytopathic toxin neutralized by Clostridium sordellii antiserum was found in the feces of seven out of 13 children with Hirschsprung's disease complicated by enterocolitis (54%). Clostridium difficile was isolated from ten of these 13 children (77%). The frequency of fecal toxin positivity, the magnitude of toxin titers, and the isolation rate of C difficile were all significantly greater in children with Hirschsprung's enterocolitis than in children whose Hirschsprung's disease was not complicated by enterocolitis or in children without Hirschsprung's disease. It is suggested that C difficile may be causally related to enterocolitis in Hirschsprung's disease, but the age distribution of positive results indicates that the major etiologic role is confined to children under three years of age. Vancomycin was found to be an effective form of treatment in the children with enterocolitis in whom it was employed.
Ulcerative colitis and its epidemiology, etiology, pathophysiology, diagnosis, clinical findings, complications, treatment, and prognosis are reviewed.
Ulcerative colitis, an inflammatory disease of unknown origin that varies in severity and clinical course, occurs most often in patients 30 to 70 years old. It appears to have a genetic component and to involve the immunological system. The cardinal symptom is usually bloody diarrhea, and the disease may be classified by either the severity of an attack, the clinical course, or by anatomic localization of inflammation.
Initial treatment of ulcerative colitis generally includes corticosteroids administered either rectally, orally, or parenterally. Oral sulfasalazine has been found useful in treating this condition and is often used for prolonged therapy to prevent relapses. Azathioprine, cromolyn sodium, antidiarrheal/anticholinergic agents, and nutritional supplements are used at times. Surgery is indicated under certain conditions and usually involves panproctocolectomy with permanent ileostomy.
The prognosis of ulcerative colitis depends upon the age of the patient, the extent of colonic involvement, and the severity of the attach.
Clindamycin is a macrolide antibiotic that has been used orally and topically in the treatment of acne vulgaris. Unfortunately, oral administration is associated with pseudomembranous colitis in up to 10% of patients; consequently, it is no longer a generally accepted form of acne therapy. Topical application is an effective, safer alternative. Topical formulations may be extemporaneously prepared or purchased as a pre-mixed hydroalcoholic solution. Adverse effects associated with topical preparations are few and mostly minor. Topical clindamycin is also used in the treatment of erythrasma, rosacea, periorificial facial dermatitis, and folliculitis.
Clostridium difficile has become one of the commonest pathogens of the lower intestinal tract. This organism appears unique in that infection almost always occurs during or after antibiotic therapy, suggesting that some component of the normal microflora prevents colonization by C. difficile. Once it has overgrown in the colon, C. difficile releases several toxins which cause tissue damage and diarrhea. Infection can range from a simple self-limited diarrheal illness to fulminant colitis with perforation and megacolon. Assay of stool filtrates reveals the presence of cytotoxin in nearly all patients with antibiotic-associated pseudomembranous colitis, and in approximately one third to one half of those with less severe infections. Effective therapy is available in the form of oral vancomycin, although the expense of this antibiotic has led to the use of oral metronidazole or bacitracin, which appear to be equally efficacious and considerably cheaper. Although we have learned a great deal about C. difficile in the past decade, a number of fascinating puzzles remain. We know very little about the immune response to this organism or its toxin, or whether a vaccine might someday be feasible. Similarly, we have very little insight into what effects antibodies exert on the normal colonic flora and how these effects allow C. difficile infection in a small percentage of patients. Studies of this pathogen will undoubtedly lead to a fuller understanding of the enormously complex and still mysterious microbial ferment which lives within our gastrointestinal tract.
ResearchGate has not been able to resolve any references for this publication.