Incidence Of Clostridium Difficile-associated Diarrhea Research Articles

Conventional and molecular diagnosis of clostridium difficile infections in a tertiary care hospital

Introduction: Indiscriminate use of broad-spectrum antibiotics has dramatically increased the incidence of Clostridium difficile-associated diarrhea (CDAD) in recent years. It is the most common cause of antibiotic-associated diarrhea (AAD) responsible for one-third of AAD cases. Aim: The aim was to study C. difficile in AAD. Objectives: The objectives were to study the prevalence of CDAD, to isolate C. difficile from AAD, and to study the molecular detection of toxin-producing strains of C. difficile. Materials and Methods: A total of 222 patients of AAD were assessed for C. difficile over a period of 2 years. Anaerobic culture for C. difficile was done on cycloserine-cefoxitin-fructose agar and brain–heart infusion agar. Enzyme-linked immunosorbent assay (ELISA) for toxin A and toxin B was used for detecting toxigenic strains of C. difficile. Identification of C. difficile and toxin-producing strains was done with the help of polymerase chain reaction (PCR). Observation and Results: Out of the total 222 cases of AAD, 20 (9%) were positive by culture and 70 (31.53%) were found to be toxin-producing C. difficile by ELISA. C. difficile was positive by PCR in 32 (14.41%); of these, 18 (56.25%) isolates were toxigenic, i.e., they possessed either the tcdA or the tcdB gene or both. Among the toxigenic isolates, 10 (31.25%) possessed both of the toxigenic genes (tcdA and tcdB) and the remaining 8 (25%) had one of the toxin genes. Only the toxin A (tcdA+ tcdB-) gene was found in 4 (12.5%) and only the toxin B (tcdA- tcdB+) gene in 4 (12.5%) of the toxigenic isolates. Conclusion: CDAD is an emerging nosocomial infection. Frequent and indiscriminate use of antibiotics has increased the prevalence of C. difficile infection. Conventional and molecular diagnosis can help to accurate diagnosis of these infections.

Diarrhoea: interventions, consequences and epidemiology in the intensive care unit (DICE-ICU): a protocol for a prospective multicentre cohort study

IntroductionDiarrhoea is a frequent concern in the intensive care unit (ICU) and is associated with prolonged mechanical ventilation, increased length of ICU stay, skin breakdown and renal dysfunction. However, its...

Proton-pump inhibitors and the risk of Clostridium difficile-associated diarrhea in high-risk antibiotics users: A population-based case-crossover study.

Given the severity and high-costs demand of Clostridium difficile-associated diarrhea (CDAD), management of risk factors is very important. Although the association between proton-pump inhibitors (PPIs) and CDAD has been established, little is known among high-risk antibiotics users. This study aimed to identify the association between PPIs and CDAD in high-risk antibiotics users by using a case-crossover design. We conducted a case-crossover study using a nationwide population-based cohort in South Korea. Participants who developed CDAD from 1 January 2003 to 31 December 2013 and had prior prescription records of both PPIs and high-risk antibiotics were included. The hazard period was 49days, and the three prior control periods had the same duration as the hazard period. The status of exposure to PPIs was assessed during the hazard and control periods in each patient and discordant pairs of exposure were used to estimate the matched odds ratio (OR). In total, 200 participants with CDAD who had histories of both PPIs and high-risk antibiotics use were included. A twofold increased risk for CDAD due to PPI use was observed (OR=2.0; 95% confidence interval, 1.2-3.2). The time-invariant variables including age group, sex, and comorbidities were proven not to modify the association between PPIs and CDAD. Our study suggested that PPIs increase the risk of developing CDAD in high-risk antibiotics users. Thus, PPIs should be used cautiously in patients requiring high-risk antibiotics in the situation of medical treatment to prevent further incidence of CDAD.

Probiotic use as prophylaxis for Clostridium difficile-associated diarrhea in a community hospital

This study was a retrospective chart review from January 1, 2015 through June 30, 2017, comparing the incidence of Clostridium difficile-associated diarrhea (CDAD) in patients taking select broad spectrum antibiotics with probiotics versus without probiotics. The purpose was to determine if probiotic use was associated with a reduction in the incidence of CDAD. A total of 5,574 hospital encounters were reviewed, showing a 0.96% incidence of CDAD in patients receiving a probiotic compared to a 2.19% incidence of CDAD in patients with no probiotic (risk ratio = 0.442; P = .00743). These findings show probiotic use was associated with a statistically significant lower incidence of positive C. difficile test results compared to no probiotic use.

Infections caused by Clostridium difficile in cancer patients

The purpose of the studywas to determine the role of antibiotics as a risk factor of Clostridium difficile-associated diarrhea in hospitalized cancer patients.Material and Methods. The study included 844 hospitalized cancer patients with diarrhea. The presence of Clostridium difficile toxins A and B in the fecal samples was determined by enzyme immunoassay.Results.Clostridium difficile toxins A and B were detected in 100 cancer patients (42 % men and 58 % women). The incidence of Clostridium difficile-associated diarrhea was higher in women than in men (р<0.02). Patients with hemoblastosis and gastrointestinal tumors were more susceptible to the development of Clostridium difficile associated diarrhea (p<0.02). The use of cephalosporin antibiotics was the main risk factor (р<0.001). In our study, 46 % of the patients took antibiotics.Conclusion.Clostridium difficile was shown to play a significant role in the development of diarrhea in cancer patients, and early detection of Clostridium difficile infection contributes to the early onset of therapy.

A Randomized, Placebo-controlled Trial of Fidaxomicin for Prophylaxis of Clostridium difficile-associated Diarrhea in Adults Undergoing Hematopoietic Stem Cell Transplantation.

Clostridium difficile-associated diarrhea (CDAD) is common during hematopoietic stem-cell transplantation (HSCT) and is associated with increased morbidity and mortality. We evaluated fidaxomicin for prevention of CDAD in HSCT patients. In this double-blind study, subjects undergoing HSCT with fluoroquinolone prophylaxis stratified by transplant type (autologous/allogeneic) were randomized to once-daily oral fidaxomicin (200 mg) or a matching placebo. Dosing began within 2 days of starting conditioning or fluoroquinolone prophylaxis and continued until 7 days after neutrophil engraftment or completion of fluoroquinolone prophylaxis/clinically-indicated antimicrobials for up to 40 days. The primary endpoint was CDAD incidence through 30 days after study medication. The primary endpoint analysis counted confirmed CDAD, receipt of CDAD-effective medications (for any indication), and missing CDAD assessment (for any reason, including death) as failures; this composite analysis is referred to as "prophylaxis failure" to distinguish from the pre-specified sensitivity analysis, which counted only confirmed CDAD (by toxin immunoassay or nucleic acid amplification test) as failure. Of 611 subjects enrolled, 600 were treated and analyzed. Prophylaxis failure was similar in fidaxomicin and placebo recipients (28.6% vs 30.8%; difference 2.2% [-5.1, 9.5], P = .278). However, most failures were due to non-CDAD events. Confirmed CDAD was lower in fidaxomicin vs placebo recipients (4.3% vs 10.7%; difference 6.4% [2.2, 10.6], P = .0014). Drug-related adverse events occurred in 15.0% of fidaxomicin recipients and 20.0% of placebo recipients. While no difference was demonstrated between arms in the primary analysis, results of the sensitivity analysis demonstrated that fidaxomicin significantly reduced the incidence of CDAD in HSCT recipients. NCT01691248.

Cost-effectiveness analysis of oral probiotics for the prevention of Clostridium difficile-associated diarrhoea in children and adolescents

The incidence of Clostridium difficile-associated diarrhoea (CDAD) in hospitalized children and adolescents has been increasing year-on-year. Paediatric CDAD places a significant economic burden on healthcare systems. Probiotics are live organisms thought to improve the microbial balance of the host, counteract disturbances in intestinal flora, and reduce the risk of colonization by pathogenic bacteria. A cost-effectiveness analysis was conducted to assess the economy of probiotics for the prevention of CDAD in children and adolescents receiving antibiotics. A decision tree model combining clinical effectiveness, utility and cost data was used. Sensitivity analyses were conducted to determine the robustness of the model outcomes. The 'oral probiotics' strategy and 'no probiotics' strategy offered patients 0.05876 and 0.056 quality-adjusted life years (QALYs) at a cost of $16,668.70 and $20,355.28, respectively. The oral probiotics strategy exhibited higher QALY and lower cost, and represents the cost-saving strategy. The results were robust for sensitivity analyses. From the perspective of the medical system, oral probiotics as a preventive strategy for CDAD in hospitalized children and adolescents receiving a therapeutic course of antibiotics reduced the risk of CDAD and represents a cost-saving strategy.

Probiotic containing Lactobacillus casei, Lactobacillus bulgaricus, and Streptococcus thermophiles (ACTIMEL) for the prevention of Clostridium difficile associated diarrhoea in the elderly with proximal femur fractures.

The incidence of Clostridium difficile associated diarrhoea (CDAD) is greater in elderly patients. Probiotics may have a beneficial effect in the prevention of CDAD. However, their effect in elderly orthopaedic patients has not been previously reported. Between April 2013 and April 2014, 105 patients admitted with femoral neck fractures, and who required 3days of antibiotics for infection of any cause, were prescribed the probiotic ACTIMEL until 3days after the last antibiotic dose. The incidence of CDAD was compared with historical controls (April 2011￢ﾀﾓApril 2012). There was no significant reduction in the incidence of CDAD in patients receiving probiotics (OR: 0.9; 95% CI 0.27￢ﾀﾓ2.91; p=0.8) and therefore we cannot recommend the use of ACTIMEL containing Lactobacillus casei, Lactobacillus bulgaricus, and Streptococcus thermophiles for this purpose in this patient group.

A prospective control study of Saccharomyces boulardii in prevention of antibiotic-associated diarrhea in the older inpatients

Objective: To study the value of Saccharomyces boulardii for the prevention of antibiotic-associated diarrhea in older inpatients. Methods: A total of 163 older patients who were treated with wide-spectrum antibiotics at least three days during January 2014 to December 2015 were randomly divided into control and study group. In study group, 81 patients were administrated with oral Saccharomyces boulardii 500 mg twice a day for 21 days. The control group was of no intervention. Morbidity rate of antibiotic-associated diarrhea and Clostridium difficile-associated diarrhea, frequency and duration of diarrhea were recorded. Results: The incidence of antibiotic-associated diarrhea in study group was significantly lower than that in control group [14.8%(12/81) vs 28.0%(23/82), P<0.05], whereas no difference was seen in the incidence of Clostridium difficile-associated diarrhea [3.7%(3/81) vs 4.9%(4/82), P>0.05] in two groups. The frequency and duration of diarrhea in the study group were significantly lower and shorter than those in control group[(4.3±1.7) times/day vs (6.9±2.0) times/day; (3.0±1.1) days vs (5.7±1.8) days, both P<0.01]. Conclusion:Saccharomyces boulardii may reduce the incidence of antibiotic-associated diarrhea therefore improving the symptom of diarrhea in older inpatients.

Effectiveness of probiotics in reducing the incidence of Clostridium difficile-associated diarrhea in elderly patients: a systematic review.

Clostridium difficile bacteria are a leading cause of infectious diarrhea. This is an anaerobic, gram-positive and spore-forming rod responsible for significant morbidity and mortality, especially among elderly hospitalized patients. Standard management of C. difficile-associated diarrhea (CDAD) consists of discontinuing a causative antibiotic, correcting fluid-electrolytes imbalance and initiating an antibiotic treatment for CDAD. Alternative approaches for prevention of CDAD include probiotics. This systematic review will provide a comprehensive, unbiased summary of the available research on the effectiveness of probiotics in decreasing the incidence of infectious diarrhea in elderly hospitalized patients. To conduct a systematic review to determine the best available evidence related to the effectiveness of probiotics in the prevention of CDAD in elderly hospitalized patients. The review question was: are probiotics effective in decreasing the incidence of CDAD in elderly hospitalized patients? The current review included studies of participants who were aged 60 years and more and who were residents of acute- and post-acute care facilities undergoing or planning to undergo antibiotic treatment for the management of any infectious conditions, except CDAD. The current review included studies that evaluated the effectiveness of probiotics for prevention of CDAD in elderly hospitalized patients in acute- and post-acute care settings compared to usual care. The current review included studies examining the following outcome measures: incidence or relapse of CDAD. Cases of CDAD were defined by presence of diarrhea and verified by positive results for stool enzyme immunoassay for toxins A and B. The current review included only experimental study designs including randomized controlled trials. The search strategy included studies published in English between 1978, when the first case of CDAD was reported, and 2015. Papers selected for retrieval were assessed by two independent reviewers for methodological quality prior to inclusion in the review using standardized critical appraisal instruments from the Joanna Briggs Institute (JBI). Data were extracted from papers included in the review using the standardized data extraction tool from the JBI Meta-Analysis of Statistics Assessment and Review Instrument. The data extracted included specific details about the interventions, populations, study methods and outcomes of significance to the review question and specific objectives. Quantitative data were pooled using statistical meta-analysis. Effect sizes were expressed as odds ratios, and their 95% confidence intervals were calculated to determine if probiotic treatment was superior to placebo in reducing CDAD incidence. Heterogeneity was assessed using the standard I statistic. Five studies were included in the review. The individual study results were conflicting, including non-significant results for four studies and statistically significant results in one that demonstrated fewer cases of CDAD among patients receiving probiotics compared to placebo. The meta-analysis finding indicated that there was no statistically significant difference in CDAD incidence in elderly hospitalized patients taking probiotics when compared to a placebo. Probiotics were not found to be more effective than placebo for reducing CDAD incidence in elderly hospitalized patients. However, studies that demonstrate improved outcomes must be examined to determine future needs for research. Studies varied with regard to the dose, frequency, method of administration (probiotic drinks versus capsule), length of administration and the number of strains of bacteria administered. Further studies are needed to evaluate the effectiveness of probiotics for CDAD prevention in this population. Clinical trials with evidence-based administration methods and meta-analyses that pool the results of studies with congruent methodologies are needed to enable conclusions to be drawn on the effectiveness of probiotic administration for CDAD prevention.

Contribution of Lactobacillus plantarum in fermented dairy products to food safety and public health

Strains of Lactobacillus plantarum recently isolated from artisanal fermented milks and milk products include L. plantarum AMA-K, L. plantarum KLDS1.0391, L. plantarum ST27, L. plantarum LL441, L. plantarum ST8K and L. plantarum BR12. The isolates exhibited in vitro antimicrobial activity against saprophytic and enteropathogenic bacteria which include Listeria monocytogenes, Staphylococcus aureus, Bacillus cereus, Escherichia coli, Clostridium difficile, Clostridium perfringens, Klebsiella pneumoniae, Enterococcus faecalis, Pseudomonas fluorescens, Salmonella typhimurium, Salmonella typhi, Salmonella enterica and Shigella flexneri. The broad antimicrobial spectrum affords ample opportunity for use of L. plantarum strains as food preservatives and probiotics in dairy products. In vivo, health benefits of L. plantarum reported in humans include increased fermentation in the hindgut, reduced intestinal load of diarrhoea-causing Enterobacteriacea, predominance of ingested L. plantarum over enteric pathogens in the intestinal microflora and reduced incidence of Clostridium difficile-associated diarrhoea.

Clinical Outcomes of Acid Suppressive Therapy Use in Hematology/Oncology Patients at an Academic Medical Center.

Acid suppressive therapy (AST)-namely, proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs)-is routinely prescribed to hospitalized patients for stress ulcer prophylaxis (SUP). To identify the incidence of and indications for AST use in the hematology/oncology population as well as to identify the occurrence of the following PPI-associated adverse events: pneumonia and Clostridium difficile-associated diarrhea (CDAD). A retrospective chart review was conducted on adult hematology/oncology patients admitted to any oncology service for ≥48 hours from October 1, 2014, to December 31, 2014. Of the 298 patients who met the inclusion criteria, 73% (n = 218) received an AST during admission. The most common indication for an AST was SUP (63%). The incidence of hospital-acquired pneumonia (HAP) was 10%, 0%, and 4% in patients who received a PPI, H2RA, and no AST, respectively (14/142 vs 0/70 vs 3/80; odds ratio [OR] for PPI vs no AST = 2.68; 95% CI = 0.75-9.63). The incidence of CDAD was 3%, 1.3%, and 1.2% in patients who received a PPI, H2RA, and no AST, respectively (4/142 vs 1/70 vs 1/80; OR for PPI vs H2RA = 1.92; 95% CI = 0.21-17.47). This is the first study to describe the incidence of and indications for AST use in the hospitalized hematology/oncology population. There was a high occurrence of AST use, particularly PPIs, in these patients at our institution. Additionally, there was a trend toward an increased risk of HAP and CDAD in patients who received AST during admission.

Probiotics are effective at preventing Clostridium difficile-associated diarrhea: a systematic review and meta-analysis.

IntroductionClostridium difficile infection (CDI) is the leading cause of antibiotic-associated diarrhea. CDI has increased in incidence and severity over the past decade, and is a growing worldwide health problem associated with substantial health care costs and significant morbidity and mortality. This meta-analysis examines the impact of probiotics on the incidence of Clostridium difficile-associated diarrhea (CDAD) among children and adults, in both hospital and outpatient settings.MethodsA comprehensive literature search of all published randomized control trials (RCTs) assessing the use of probiotics in the prevention of CDAD in patients receiving antibiotic therapy was conducted, and the incidence of CDAD was analyzed.ResultsTwenty-six RCTs involving 7,957 patients were analyzed. Probiotic use significantly reduced the risk of developing CDAD by 60.5% (relative risk [RR] =0.395; 95% confidence interval [CI], 0.294–0.531; P<0.001). Probiotics proved beneficial in both adults and children (59.5% and 65.9% reduction), especially among hospitalized patients. Lactobacillus, Saccharomyces, and a mixture of probiotics were all beneficial in reducing the risk of developing CDAD (63.7%, 58.5%, and 58.2% reduction).ConclusionProbiotic supplementation is associated with a significant reduction in the risk of developing CDAD in patients receiving antibiotics. Additional studies are required to determine the optimal dose and strain of probiotic.

Clinical characteristics of Clostridium difficile-associated diarrhea among patients in a tertiary care center in China.

Objective:This study investigated the incidence, risk factors, and clinical characteristics of Clostridium difficile-associated diarrhea (CDAD) in Chinese patients.Methods:Fecal specimens of patients with antibiotic-associated diarrhea (AAD) were collected to test C. difficile toxin A and B using enzyme-linked fluorescent assay to identify CDAD. By adopting a nested case-control design, the matched people (ratio 1:3) without AAD were included as controls.Results:Out of 56,172 inpatients, 39,882 (71.0%) used antibiotics, 470 suffered from AAD, and 93 were diagnosed with CDAD. The incidence of nosocomial CDAD was 166 per 100,000. The proportion of CDAD in AAD was 19.8%. CDAD patients presented with more severe clinical manifestations and exhibited more concurrent illness. Logistic regression analysis showed the risk factors of CDAD: advanced age, nasogastric tube-feeding, high APACHE II scores, high level of serum C-reaction protein, low level of serum albumin, severe underlining disease or comorbidity, and number of antibiotic intake. Twenty-nine patients (31.2%) were cured with vancomycin, 54 (58.1%) were cured after dual therapy of vancomycin plus metronidazole, 7 (7.5%) died of underlying diseases aggravated with CDAD, and 3 (3.2%) were transferred to other hospitals for personal reasons.Conclusion:The incidence of nosocomial CDAD in China was high. Some risk factors could predispose CDAD.

A Subgroup Analysis of Patients Undergoing Autologous and Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in Deflect-1: A Double-Blind, Randomized Study of Fidaxomicin Vs. Placebo for Prophylaxis Against C. Difficile Infection

Introduction: Clostridium difficile-associated diarrhea (CDAD) is a common complication during HSCT that has been associated with increased morbidity and mortality. CDAD has been reported to occur in 6 to 30% of HSCT patients. An ideal agent for prevention of CDAD has not been established. Fidaxomicin (FDX) is bactericidal against C. difficile, has low systemic absorption, provides a prolonged post-antibiotic effect, and is currently approved for the treatment of CDAD. The efficacy and safety of low dose FDX (200mg once daily) for prevention of CDAD were evaluated in both autologous (AUTO) and allogenic (ALLO) HSCT patients receiving fluoroquinolone (FQ) prophylaxis.Methods: HSCT patients were randomized to receive FDX 200 mg once daily (QD) or placebo (PLA) from start of conditioning therapy or FQ prophylaxis until 7 days after post-transplant engraftment (ANC >500/mm3) or completion of FQ prophylaxis. Randomization was stratified by type of HSCT (AUTO vs. ALLO). Patients were contacted twice weekly for 30 days and then weekly through 60 days post-prophylaxis for symptoms; CDAD was confirmed by toxin testing or PCR. The incidence of CDAD from start of prophylaxis up to 30 days and 60 days post-treatment were primary and secondary endpoints, respectively. For the primary analysis, failures were defined as patients with confirmed CDAD, as well as those who had missing data for the primary endpoint assessment (due to death or discontinuations resulting from adverse events, protocol non-compliance, lost follow-up, or any other reasons) and those who received any CDAD-effective medication (without confirmed CDAD). Sensitivity analyses, including an analysis that defined failure as confirmed CDAD, were prospectively defined for the overall population. These same analyses were performed for the ALLO and AUTO subgroups.Results: Of 611 enrolled patients, 600 were evaluable: 352 (59%) in AUTO and 248 (41%) in ALLO subgroups. The primary analysis for the primary endpoint did not show a significant reduction in incidence of CDAD with FDX prophylaxis (28.6% FDX vs. 30.8% PLA, p = 0.28). Secondary endpoint results were similar. However, the incidence of confirmed CDAD for up to 30 days was significantly lower in AUTO, ALLO, and overall in HSCT patients receiving prophylactic FDX versus PLA (see table). There were similar trends for 60 day post-treatment results. Overall, serious adverse events (AEs) and AEs resulting in death were more frequent in the ALLO vs. AUTO subgroup. In both subgroups, no differences in drug-related serious and non-serious AEs were seen between FDX and PLA.TableIncidence of Confirmed CDAD, 30d Post-treatmentAUTOALLOTotalFDX (%)5/176 (2.8%)8/125 (6.4%)13/301 (4.3%)PLA (%)14/176 (8.0%)18/123 (14.6%)32/299 (10.7%)PLA-FDX, %5.18.26.4Wald p-value0.01630.01660.0014Incidence of Confirmed CDAD, 60d Post-treatmentFDX (%)6/176 (3.4%)11/125 (8.8%)17/301 (5.6%)PLA (%)14/176 (8.0%)18/123 (14.6%)32/299 (10.7%)PLA-FDX, %4.55.85.1Wald p-value0.03210.07590.0117Conclusions: For the primary endpoint (failure of prophylaxis due to confirmed CDAD or non-CDAD events), the efficacy of FDX and PLA were similar. However, in both AUTO and ALLO HSCT patients, prophylactic FDX significantly reduced the incidence of confirmed CDAD and was not associated with drug-related adverse events. DisclosuresDugan:Cubist/Merck & Co., Inc.: Research Funding. Winston:Cubist/Merck & Co., Inc.: Research Funding. Morris:Cubist/ Merck & Co., Inc.: Research Funding. Williams:Merck & Co., Inc.: Employment. Broyde:Merck & Co., Inc.: Employment. Sears:Merck & Co., Inc.: Employment.

Effect of Nutritional Status on Length of Hospital Stay in Patients With Clostridium difficile-Associated Diarrhea

Introduction:Clostridium difficile associated diarrhea (CDAD) is one of the most common nosocomial infections in hospitals and long term care facilities. Low serum albumin and serum protein, which are surrogates of nutritional status, are associated with increased incidence of CDAD and worse outcomes in patients with CDAD. However, these measures are crude and non-specific and there are no studies to date which demonstrate a direct association between the nutritional status - as assessed by standardized, replicable criteria - with outcomes of patients with CDAD. We aim to show that an Aspen Nutritional Index (ASI) is a more valid and accurate instrument to measure underlying malnutrition in patients with CDAD. Methods: We performed a retrospective cross-sectional study from April 2013 to June 2014. Hospitalized patients ≥ 18 years of age were included and divided into two groups: study group (diarrhea with a positive assay for antigen and toxins for c. difficile) and a control group (patients with negative assay for antigen and toxin for c. difficile). Each group was then subdivided into a non-malnourished group and a malnourished group according to the ASI (based on the 2012 ASPEN guidelines). Demographic data, Charlson comorbidity index (CMI), nutritional assessment, and, length of stay (LOS) were studied for each patient. All-cause mortality was also recorded for secondary outcomes. The inclusion criteria, exclusion criteria and all definitions were defined prior to the study. Results: A total of 314 patients were included: 148 patients in the study group (89 malnourished and 59 non-malnourished) and 166 in the control group (132 malnourished and 34 non-malnourished). Malnourished patients with CDAD had the longest LOS compared to other groups (Table 1). Malnourished patients with CDAD compared to non-malnourished control patients had a significantly increased LOS, mean±S.E. LOS (16.73±1.69 versus 11.35±1.33 days) (p=0.014). In addition, malnourished patients with CDAD had the highest all-cause mortality compared to the other groups (Table 2). All-cause mortality rate of malnourished patients with CDAD compared to non-malnourished control patients was 24.7% versus 5.9% (p=0.021). Mean CMI was 7±1 for all groups.Table 1: Mean length of stay between groups(in days)Table 2: Percentage all-cause mortalityConclusion: Malnourishment leads to prolonged LOS and increases all-cause mortality in CDAD. The ASI is the most accurate measure of underlying nutritional status and should be calculated in all patients with, or at risk for CDAD.

The effectiveness of probiotics in reducing the incidence of Clostridium difficile associated diarrhea in elderly patients: a systematic review protocol.

REVIEW QUESTION / OBJECTIVE The objective of this review is to assess the effectiveness of probiotics in reducing the incidence of Clostridium difficile-associated diarrhea in elderly patients (60 years and older) who are residents of acute- and post-acute care facilities. INCLUSION CRITERIA Types of participants This review will consider studies that include participants aged 60 years and older who are residents of acute- and post-acute care facilities and are undergoing or planning to undergo antibiotic treatment. Studies that include participants undergoing treatment for Clostridium difficile associated diarrhea will be excluded. Types of intervention(s) This review will consider studies that evaluate the effectiveness of probiotics for prevention of Clostridium difficile associated diarrhea in elderly patients in acute- and post-acute care settings compared to usual care. Any brand or strength of a probiotic product will be considered for the review. The review will also include studies examining various forms of probiotics, such as yogurt, buttermilk, combination products or capsules. Types of outcomes This review will consider studies that include the following outcome measures: incidence or relapse of Clostridium difficile associated diarrhea. Cases of Clostridium difficile associated diarrhea will be defined by presence of diarrhea and verified by positive results for stool enzyme immunoassay for toxins A and B. Absence of diarrhea verified by negative results for stool enzyme immunoassay for toxins A and B.

The potential use of cholestyramine to reduce the risk of developing Clostridium difficile-associated diarrhoea in patients receiving long-term intravenous ceftriaxone

Intravenous pharmacotherapy with the third-generation cephalosporin ceftriaxone is unfortunately associated with a relatively high incidence of Clostridium difficile-associated diarrhoea. Cholestyramine (colestyramine) is an anion-binding resin which can bind luminal C.difficile toxin A (TcdA) and toxin B (TcdB) and which may be beneficial in the treatment of recurrent antibiotic-associated pseudomembranous colitis. We therefore hypothesised that concomitant oral cholestyramine might reduce the risk of C.difficile-associated diarrhoea in patients receiving long-term intravenous ceftriaxone. A pilot study was carried out in which it was found that only three out of 46 (6.5%) such patients being treated with 2g ceftriaxone daily for Lyme borreliosis, who also received 4g cholestyramine daily, developed C.difficile-associated diarrhoea. This is smaller than a published report of the incidence of this complication in six out of 26 (23.1%) patients following 1–3days’ treatment with 1g intravenous ceftriaxone, but without oral cholestyramine (p=0.06). We therefore recommend that a larger, double-blind placebo-controlled trial be carried out to test this hypothesis.

Safety and clinical outcomes of carbapenem de-escalation as part of an antimicrobial stewardship programme in an ESBL-endemic setting.

To evaluate the safety and clinical outcomes of patients who received carbapenem de-escalation as guided by an antimicrobial stewardship programme (ASP) in a setting where ESBL-producing Enterobacteriaceae are endemic. Patients receiving meropenem or imipenem underwent a prospective ASP review for eligibility for de-escalation according to defined institutional guidelines. Patients in whom carbapenem was de-escalated or not de-escalated, representing the acceptance and rejection of the ASP recommendation, respectively, were compared. The primary outcome was the clinical success rate; secondary outcomes included the 30 day readmission and mortality rates, the duration of carbapenem therapy, the incidence of adverse drug reactions due to antimicrobials, the acquisition of carbapenem-resistant Gram-negative bacteria and the occurrence of Clostridium difficile-associated diarrhoea (CDAD). The de-escalation recommendations for 300 patients were evaluated; 204 (68.0%) were accepted. The patient demographics and disease severity were similar. The clinical success rates were similar [de-escalated versus not de-escalated, 183/204 (89.7%) versus 85/96 (88.5%), P=0.84], as was the survival at hospital discharge [173/204 (84.8%) versus 79/96 (82.3%), P=0.58]. In the de-escalated group, the duration of carbapenem therapy was shorter (6 versus 8 days, P<0.001), the rate of adverse drug reactions was lower [11/204 (5.4%) versus 12/96 (12.5%), P=0.037], there was less diarrhoea [9/204 (4.4%) versus 12/96 (12.5%), P=0.015], there was a lower incidence of carbapenem-resistant Acinetobacter baumannii acquisition [4/204 (2.0%) versus 7/96 (7.3%), P=0.042] and there was a lower incidence of CDAD [2/204 (1.0%) versus 4/96 (4.2%), P=0.081]. This study suggests that the ASP-guided de-escalation of carbapenems led to comparable clinical success, fewer adverse effects and a lower incidence of the development of resistance. This approach is safe and practicable, and should be a key component of an ASP.

Corticosteroid use is associated with a reduced incidence of Clostridium difficile-associated diarrhea: A retrospective cohort study

The impact of corticosteroid use on the incidence of Clostridium difficile-associated diarrhea (CDAD) was examined retrospectively in 532 patients receiving antibiotic treatment for respiratory infections. As determined by logistic regression, corticosteroids were associated with a decreased incidence of CDAD (Odds Ratio 0.12, 95% Confidence Interval 0.006–0.95).