Volume 7, Number 12;  January 22, 2007 - Clostridium Difficile Diarrhea

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Unique Identifier [PMID]: 17116920

Authors: Bartlett JG.

Institution: Department of Medicine, John Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. jb@jhmi.edu

Title: Narrative review: the new epidemic of Clostridium difficile-associated enteric disease. [Review] [77 refs]

Source: Annals of Internal Medicine. 145(10):758-64, 2006 Nov 21.

Abstract: Antibiotic-associated diarrhea and colitis were well established soon after antibiotics became available. Early work implicated Staphylococcus aureus, but in 1978 Clostridium difficile became the established pathogen in the vast majority of cases. In the first 5 years (1978 through 1983), the most common cause was clindamycin, the standard diagnostic test was the cytotoxin assay, and standard management was to withdraw the implicated antibiotic and treat with oral vancomycin. Most patients responded well, but 25% relapsed when vancomycin was withdrawn. During the next 20 years (1983 through 2003), the most commonly implicated antibiotics were the cephalosporins, which reflected the rates of use; the enzyme immunoassay replaced the cytotoxin assay because of speed of results and technical ease of performance; and metronidazole replaced vancomycin as standard treatment, and principles of containment hospitals became infection control and antibiotic control. During the recent past (2003 to 2006), C. difficile has been more frequent, more severe, more refractory to standard therapy, and more likely to relapse. This pattern is widly distributed in the United States, Canada, and Europe and is now attributed to a new strain of C. difficile designated BI, NAP1, or ribotype 027 (which are synonymous terms). This strain appears more virulent, possibly because of production of large amounts of toxins, and fluoroquinolones are now major inducing agents along with cephalosporins, which presumably reflects newly acquired in vitro resistance and escalating rates of use. The recent experience does not change principles of management of the individual patient, but it does serve to emphasize the need for better diagnostics, early recognition, improved methods to manage severe disease and relapsing disease, and greater attention to infection control and antibiotic restraint. [References: 77]

Publication Type: Journal Article. Review.

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Unique Identifier [PMID]: 17116441

Authors: Bouza E. Burillo A. Munoz P.

Institution: Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Maranon, Universidad Complutense, Dr. Esquerdo 46, 28007 Madrid, Spain.

Title: Antimicrobial therapy of Clostridium difficile-associated diarrhea. [Review] [227 refs]

Source: Medical Clinics of North America. 90(6):1141-63, 2006 Nov.

Abstract: Clostridium difficile-associated diarrhea (CDAD) is the most common etiologically-defined cause of hospital-acquired diarrhea. Caused by the toxins of certain strains of C difficile, CDAD represents a growing concern, with epidemic outbreaks in some hospitals where very aggressive and difficult-to-treat strains have recently been found. Incidence of CDAD varies ordinarily between 1 to 10 in every 1,000 admissions. Evidence shows that CDAD increases morbidity, length of stay, and costs. This article described the clinical manifestations of CDAD, related risk factors, considerations for confirming CDAD, antimicrobial and non-antimicrobial treatment of CDAD, and issues related to relapses. The article concludes with a discussion of recent epidemic outbreaks involving CDAD. [References: 227]

Publication Type: Journal Article. Review.

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Unique Identifier [PMID]: 16027434

Authors: Dendukuri N. Costa V. McGregor M. Brophy JM.

Institution: Technology Assessment Unit, McGill University Health Centre, McGill University, Montreal, Que. nandini.dendukuri@mcgill.ca

Title: Probiotic therapy for the prevention and treatment of Clostridium difficile-associated diarrhea: a systematic review.[see comment][erratum appears in CMAJ. 2005 Aug 16;173(4):345]. [Review] [27 refs]

Source: CMAJ Canadian Medical Association Journal. 173(2):167-70, 2005 Jul 19.

Abstract: BACKGROUND: The recent increase in the number and severity of cases of nosocomial Clostridium difficile-associated diarrhea (CDAD) has prompted interest in the use of probiotics for the prevention and treatment of this disease. We performed a systematic review of randomized controlled trials to assess the effectiveness of probiotic therapy. METHODS: We searched the PubMed, EMBASE, INAHTA, HEN and Cochrane Collaboration databases to identify trials in which the prevention or treatment of CDAD with probiotic therapy was the primary or secondary outcome. We extracted data on the number of patients randomly assigned to receive probiotic or placebo, the number of patients with CDAD, the type of probiotic, criteria for diagnosing CDAD, persistence of infection after treatment, compliance and adverse effects. RESULTS: We identified 4 eligible studies in which prevention (n = 1) or treatment (n = 3) of CDAD was the primary outcome. The benefit of probiotic therapy seen in 2 of the studies was restricted to subgroups characterized by severe CDAD and increased use of vancomycin. The remaining 2 studies were too methodologically flawed for us to draw meaningful conclusions. We also identified 4 trials in which prevention of antibiotic-associated diarrhea with probiotics was the primary outcome and prevention of CDAD a secondary outcome. These studies were limited primarily by too few CDAD cases and provided no evidence of effective prophylaxis. Overall, heterogeneity in choice and dose of probiotic and in criteria for diagnosing CDAD makes it difficult to synthesize information from the 8 studies. INTERPRETATION: Studies conducted to date provide insufficient evidence for the routine clinical use of probiotics to prevent or treat CDAD. Better designed and larger studies are needed. [References: 27]

Publication Type: Journal Article. Review.

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Unique Identifier [PMID]: 15674956

Authors: Bricker E. Garg R. Nelson R. Loza A. Novak T. Hansen J.

Title: Antibiotic treatment for Clostridium difficile-associated diarrhea in adults. [Review] [31 refs]

Source: Cochrane Database of Systematic Reviews. (1):CD004610, 2005.

Abstract: BACKGROUND: Clostridium difficile (C. difficile) is recognized as a frequent cause of antibiotic-associated diarrhea and colitis. OBJECTIVES: The aim of this review is to establish the efficacy of antibiotic therapy for C. difficile-associated diarrhea (CDAD), to identify the most effective antibiotic treatment for CDAD in adults and to determine the need for stopping the causative antibiotic during therapy. SEARCH STRATEGY: MEDLINE (1966 to 2003), EMBASE (1980 to 2003), Cochrane Central Database of Controlled Trials and the Cochrane IBD Review Group Specialized Trials Register were searched using the following search terms: "pseudomembranous colitis and randomized trial"; "Clostridium difficile and randomized trial"; "antibiotic associated diarrhea and randomized trial". SELECTION CRITERIA: Only randomized, controlled trials assessing antibiotic treatment for CDAD were included in the review. Probiotic trials are excluded. The following outcomes were sought: initial resolution of diarrhea; initial conversion of stool to C. difficile cytotoxin and/or stool culture negative; recurrence of diarrhea; recurrence of fecal C. difficile cytotoxin and/or positive stool culture; patient response to cessation of prior antibiotic therapy; sepsis; emergent surgery: fecal diversion or colectomy; and death. DATA COLLECTION AND ANALYSIS: Data were analyzed using the MetaView statistical package in Review Manager. For dichotomous outcomes, relative risks (RR) and 95% confidence intervals (CI) were derived from each study. When appropriate, the results of included studies were combined for each outcome. For dichotomous outcomes, pooled RR and 95% CI were calculated using a fixed effect model, except where significant heterogeneity was detected, at which time the random effects model was used. Data heterogeneity was calculated using MetaView. MAIN RESULTS: Of eleven studies identified, two were subsequently excluded because patients were stool positive for C. difficile, but did not have diarrhea or because the study was not a randomized controlled trial. All of the remaining nine studies involved patients with diarrhea who recently received antibiotics for an infection other than C. difficile. The definition of diarrhea ranged from at least two loose stools per day with an associated symptom such as rectal temperature > 38(o)C, to at least six loose stools in 36 hours. In terms of symptomatic cure, metronidazole, bacitracin and fusidic acid were not shown to be less effective than vancomycin. Teicoplanin may be slightly more effective than vancomycin with a relative risk of 1.21 [95% CI 1.00 to 1.46] and a p-value of 0.06. In terms of initial symptomatic resolution, vancomycin is more effective than placebo with a relative risk of 6.75 [95% CI 1.16 to 48.43] and a p-value of 0.03. This result should be interpreted with caution given the small number of patients in this comparison (12 in the vancomycin group and nine in the placebo group) and the poor methodological quality of the trial. Metronidazole, bacitracin, teicoplanin, fusidic acid and rifaximine are as effective as vancomycin for initial symptomatic resolution. The other secondary outcomes measured in this review: surgery, sepsis and death occurred infrequently in all of the studies. AUTHORS' CONCLUSIONS: Current evidence leads to uncertainty whether mild CDAD needs to be treated. Patients with mild CDAD may resolve their symptoms as quickly without treatment. The only placebo-controlled study shows vancomycin's superior efficacy. However, this result should be treated with caution due to the small number of patients enrolled and the poor methodological quality of the trial. The Johnson study of asymptomatic carriers also shows that placebo is better than vancomycin or metronidazole for eliminating C. difficile in stool during follow-up. If one does decide to treat, then two goals of therapy need to be kept in mind: improvement of the patient's clinical condition and prevention of spread of C. difficile infection to other patients. Given these two considerations, one should choose the antibiotic that brings both symptomatic cure and bacteriologic cure. In this regard, teicoplanin appears to be the best choice because the available evidence suggests that it is better than vancomycin for bacteriologic cure and has borderline superior effectiveness in terms of symptomatic cure. Teicoplanin is not readily available in the United States, which must be taken into account when making treatment decisions in that country. [References: 31]

Publication Type: Journal Article. Meta-Analysis. Review.

Resident Report / Department of Medicine & Grady Branch Library

Emory University School of Medicine

2006 Edition

Participating Faculty:  Carlos Del Rio MD  / Joyce Doyle MD / Lorenzo Difrancesco MD / Joel Mermis MD / Maunank Shah MD

Contact: Karl Woodworth