Antibiotic-associated Diarrhea In Adults Research Articles

Anti-S-layer monoclonal antibodies impact Clostridioides difficile physiology

ABSTRACT Clostridioides difficile (C. difficile), a gram-positive anaerobic and spore-forming bacterium, is the leading cause of nosocomial antibiotic-associated diarrhea in adults which is characterized by high levels of recurrence and mortality. Surface (S)-layer Protein A (SlpA), the most abundantly expressed protein on the bacterial surface, plays a crucial role in the early stages of infection although the nature of its involvement in C. difficile physiology is yet to be fully understood. Anti-S-layer antibodies have been identified in the sera of convalescent patients and have been correlated with improved outcomes of C. difficile infection (CDI). However, the precise mechanisms by which anti-S-layer antibodies confer protection to the host remain unknown. In this study, we report the first monoclonal antibodies (mAbs) targeting the S-layer of reference strain 630. Characterization of these mAbs unraveled important roles for the S-layer protein in growth, toxin secretion, and biofilm formation by C. difficile, with differential and even opposite effects of various anti-SlpA mAbs on these functions. Moreover, one anti-SlpA mAb impaired C. difficile growth and conferred sensitivity to lysozyme-induced lysis. The results of this study show that anti-S-layer antibody responses can be beneficial or harmful for the course of CDI and provide important insights for the development of adequate S-layer-targeting therapeutics.

Effects of <i>Lactobacillus delbrueckii</i> TS1-06 probiotic strain on the size of myocardial infarction in Wistar rats with systemic inflammatory response syndrome

Experimental medicine provides the scientific community with a plethora of information on therapeutic efficacy of probiotic strains. However, from the point of view of evidence-based medicine, the list of disorders controlled by probiotics is limited to antibiotic-associated diarrhea in adults and children, Clostridium difficile-associated diarrhea, acute infectious diarrhea in children and adults, eradication therapy, ulcerative colitis and irritable bowel syndrome. Recently, these indications are also amended by well-validated clinical guidelines for the usage of probiotic preparations, in order to modulate immunity. Given the permeability of gastrointestinal and immune system barriers for pathogenic and opportunistic microbiota, it seems logical to assume the effectiveness of probiotics as potential symbiotic regulators of nervous and cardiovascular systems. It should also be taken into account that metabolic disorders, e.g., obesity, with a low-intensity inflammatory response and characteristic cytokine pattern, are acquired as a gain of human civilization. In this regard, we propose a scientific hypothesis about the effectiveness of probiotic microbial strains in increasing myocardial resistance to ischemic-reperfusion injury, due to their ability to block individual links of the cytokine cascade during the development of inflammatory response, for its subsequent translation into clinical practice.The development and validation of a new experimental model of systemic inflammatory response syndrome (SIRS) in male Wistar rats, including obesity, acute inflammatory process of the colon, and antibiotic-induced dysbiosis, became basic to the study of efficacy of probiotic drugs in terms of myocardial resistance to ischemicreperfusion injury (IRI). Rats with SIRS showed a significantly increased size of the infarction area (+28%) upon experiments with isolated perfused heart under global ischemia-reperfusion conditions. Significant changes in the leukocyte formula and immunological parameters associated with SIRS were corrected by introduction of a mixture of probiotic strains L. acidophilus (LA-5) and B. animalis subsp. lactis (BB-12), and the isolated strain L. delbrueckii TS1-06. In both groups with probiotic correction, there was a decrease in the infarction area compared to the SIRS group. General and specific changes in IL-2, transforming growth factor-b (TGF-b) and tumor necrosis factor-a (TNFa) were noted. The reduction of myocardial infarction by probiotics may be related to the blocking of first-order cytokines, which leads to a «break» of proinflammatory cascade. A need for in-depth study of cardioprotective mechanisms mediated by probiotics was confirmed due to their potential usage as a symbiotic alternative to biological drugs which block the main pro-inflammatory cytokines.

Regulation of Clostridial Toxin Gene Expression: A Pasteurian Tradition.

The alarming symptoms attributed to several potent clostridial toxins enabled the early identification of the causative agent of tetanus, botulism, and gas gangrene diseases, which belongs to the most famous species of pathogenic clostridia. Although Clostridioides difficile was identified early in the 20th century as producing important toxins, it was identified only 40 years later as the causative agent of important nosocomial diseases upon the advent of antibiotic therapies in hospital settings. Today, C. difficile is a leading public health issue, as it is the major cause of antibiotic-associated diarrhea in adults. In particular, severe symptoms within the spectrum of C. difficile infections are directly related to the levels of toxins produced in the host. This highlights the importance of understanding the regulation of toxin synthesis in the pathogenicity process of C. difficile, whose regulatory factors in response to the gut environment were first identified at the Institut Pasteur. Subsequently, the work of other groups in the field contributed to further deciphering the complex mechanisms controlling toxin production triggered by the intestinal dysbiosis states during infection. This review summarizes the Pasteurian contribution to clostridial toxin regulation studies.

Prevalence and Seasonality of Clostridiodes difficile over 12Years at a Tertiary Hospital in Brazil.

Clostridioides difficile is the main pathogen responsible for antibiotic-associated diarrhea in adults. Besides its challenging diagnosis, C. difficile infection (CDI) causes substantial morbidity and mortality. Commercially, there are assays with different targets and performances in sensitivity and specificity. The objectives of this study were to: (1) evaluate the prevalence and seasonal variability of CDI rates at a tertiary hospital in southern Brazil over 12years and (2) determine the impact of using a two-step algorithm test in the laboratory diagnosis. Between January 2007 and May 2019, fecal samples from 2275 patients were analyzed in a cross-sectional study. Four commercial tests were adopted for the diagnosis of CDI, the immunochromatographic test for toxin A from 2007 to 2010; the enzyme-linked immunosorbent assay method for toxins A and B from 2011 to March 2017; and the rapid enzyme immunoassay (EIA) for GDH and toxins A and B, associated with a Polymerase Chain Reaction (PCR) for the toxin B gene from June 2017 to 2019. The annual prevalence was 8.7% from 2007 to March 2017, increasing between June 2017 and 2019 to 14.7% when the C. diff Quik Chek Complete + GeneXpert C. difficile (two-step algorithm) test was adopted. The number of samples (691) and percentage of CDI cases (10.5%) were higher in winter, but the difference has no statistical significance (P > 0.05). An accurate diagnosis and adequate knowledge of the local seasonality of CDI allow the effective implementation of prevention and control strategies for nosocomial CDI, in addition to effective treatment for patients.

Association Between Clostridium innocuum and Antibiotic-Associated Diarrhea in Adults and Children: A Cross-sectional Study and Comparative Genomics Analysis.

A recent study from Taiwan suggested that Clostridium innocuum may be an unrecognized cause of antibiotic-associated diarrhea (AAD) and clinically indistinguishable from Clostridioides difficile infection. Our objective was to compare C. innocuum prevalence and strain between those with AAD and asymptomatic controls. In this cross-sectional study, we collected stool from 200 individuals with AAD and 100 asymptomatic controls. We evaluated the association between AAD and C. innocuum in stool using anaerobic culture and quantitative polymerase chain reaction (qPCR). To identify strain-specific associations with AAD, we performed whole-genome sequencing of C. innocuum isolates using Illumina MiSeq and constructed comparative genomics analyses. C. innocuum was isolated from stool of 126/300 (42%) subjects and more frequently from asymptomatic controls than AAD subjects (50/100 [50%] vs 76/200 [38%], respectively; P = .047). C. innocuum isolation frequency was not associated with AAD in either the adult or pediatric subgroups. C. innocuum and C. difficile were frequently co-prevalent in individuals with and without diarrhea. There were no phylogenetic differences or accessory genome associations between C. innocuum isolates from AAD subjects and asymptomatic controls. C. innocuum was frequently isolated and at a greater frequency in asymptomatic controls than those with AAD. We did not identify strain lineages or accessory genomic elements associated with AAD. These data highlight that differentiating C. innocuum-associated diarrhea from asymptomatic colonization, and differentiating diarrhea caused by C. difficile from C. innocuum, are clinical microbiology challenges that require additional investigation to identify host-specific factors and/or biomarkers that distinguish these conditions.

Impact of Concurrent Use of Probiotics on Risk of Antibiotic Associated Diarrhoea in Adults

Antibiotics are one of the most prescribed medications worldwide. It is given to treat a wide range of infections and diseases. However, usage of antibiotics is associated with several side effects. The most frequently reported side effect is diarrhoea since antibiotics affect the gastrointestinal microbial environment. Antibiotic associated diarrhoea refers to the diarrhoea that develops at the initiation of the antibiotic therapy and can extend even up to six or more weeks after termination of the therapy. The prevalence of antibiotic associated diarrhoea ranges from 5% to 39% and is associated with significant morbidity and mortality. Antibiotic associated diarrhoea can be caused by any antibiotic used although the risk is higher for broad-spectrum antibiotics since they primarily target anaerobes and are poorly absorbed. Probiotics aid in reducing the risk of antibiotic associated diarrhoea. The purpose of this research is to review the available information about the impact of concurrent use of probiotics on risk of antibiotic-associated diarrhoea in adults. Various studies in the literature suggest of concurrent use of probiotics in treatment and prevention of antibiotic associated diarrhoea. Probiotics have been widely recommended as a robust and reliable strategy to lessen the negative effects of antibiotics on gastrointestinal function. Probiotics have a beneficial role in improving the gut health thus lowering the incidence of antibiotic associated diarrhoea if administered concurrently. Probiotics are generally well-tolerated and have minimum side effects. However more clinical research is needed to establish the guidelines for their concurrent use with antibiotic therapy to prevent antibiotic associated diarrhoea.

Probiotics for the prevention of antibiotic-associated diarrhoea: a systematic review and meta-analysis

ObjectiveTo evaluate existing evidence for the use of probiotics in preventing antibiotic-associated diarrhoea (AAD) in adults.DesignSystematic review and meta-analysis of randomised controlled trials (RCTs).Data sourcesWe performed a literature search of...

Probiotics for the Prevention of Antibiotic-associated Diarrhea in Adults: A Meta-Analysis of Randomized Placebo-Controlled Trials.

Objective:This meta-analysis aims to combine the latest research evidence to assess the effect of probiotics on preventing antibiotic-associated diarrhea (AAD) in adults.Methods:PubMed, Cochrane Library, EMBASE, and Web of Science were searched for randomized placebo-controlled trials on probiotics preventing AAD. A random or fixed effect model was used to combine the incidence of AAD (primary outcome) and the adverse event rates. The authors performed subgroup analyses to explore the effects of different participants population, probiotics species, and dosage.Results:Thirty-six studies were included with 9312 participants. Probiotics reduced the incidence of AAD by 38% (pooled relative risk, 0.62; 95% confidence interval, 0.51-0.74). The protective effect of probiotics was still significant when grouped by reasons for antibiotics treatment, probiotic duration, probiotic dosage, and time from antibiotic to probiotic. However, there were no statistically significant increased adverse events in the probiotics group (relative risk, 1.00; 95% confidence interval, 0.87-1.14).Conclusions:This updated meta-analysis suggested that using probiotics as early as possible during antibiotic therapy has a positive and safe effect on preventing AAD in adults. Further studies should focus on the optimal dosage and duration of probiotics to develop a specific recommendation.

Impact of subinhibitory concentrations of metronidazole on proteome of Clostridioides difficile strains with different levels of susceptibility.

Clostridioides difficile is responsible for various intestinal symptoms from mild diarrhea to severe pseudomembranous colitis and is the primary cause of antibiotic-associated diarrhea in adults. Metronidazole was the first-line treatment for mild to moderate C. difficile infections for 30 years. However, clinical failure and recurrence rates of metronidazole is superior to oral vancomycin and metronidazole is now recommended only as an alternative to vancomycin or fidaxomicin, for an initial non-severe infection. The mechanisms of treatment failure and infection recurrence remain unclear. Given the poor fecal concentrations of metronidazole, the bacteria may be exposed to subinhibitory concentrations of metronidazole and develop adaptation strategy, which is likely to be the origin of an increase in treatment failures. In this study, a proteomic approach was used to analyze changes in the proteome of two strains with different levels of susceptibility to metronidazole in the presence of subinhibitory concentrations of this antibiotic. The two strains were grown to stationary phase: CD17-146, a clinical C. difficile isolate with reduced susceptibility to metronidazole, and VPI 10463, a metronidazole susceptible strain. Our study revealed that, whatever the strain, subinhibitory concentrations of metronidazole modified the amount of proteins involved in protein biosynthesis, glycolysis, and protection against stress induced by metronidazole, as well as in DNA repair. Several proteins involved in stress response are known to be synthesized under the control of Sigma factor B, which suggests a close link between Sigma factor B and metronidazole. Interestingly, impact of metronidazole on protein production for VPI 10463 strain differed from CD17-146 strain, for which the amount of two proteins involved in biofilm formation of CD17-146 were modified by metronidazole.

Probiotic Yogurt for the Prevention of Antibiotic-associated Diarrhea in Adults: A Randomized Double-blind Placebo-controlled Trial.

To evaluate the effect of yogurt supplemented with probiotic bacteria on the prevention of antibiotic-associated diarrhea (AAD) in hospitalized patients. Diarrhea following antibiotic administration is a frequent clinical problem. The usefulness of probiotics for the prevention of AAD in the hospitalized adult population remains unclear. A randomized, double-blind, placebo-controlled clinical trial was conducted in hospitalized patients who started antibiotic treatment. Patients were randomized (2:2:1) to receive a daily amount of 200 mL of placebo-yogurt (Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus), 200 mL of probiotic yogurt (previous plus Lactobacillus acidophilus La-5, Bifidobacterium animalis subsp. lactis Bb-12 and Lactobacillus casei subsp. casei Lc-01 or no yogurt (unblinded control) within 48 hours of beginning the antibiotic therapy and up to 5 days after stopping the antibiotic. Patients were followed up with for 1 month to determine occurrence of diarrhea. We included 314 patients, mean age 76 years. The rate of diarrhea was 23.0% in the probiotic group versus 17.6% in the placebo group, absolute risk reduction -5.35% (95% confidence interval, -15.4% to 4.7%; P=0.30). Rate of diarrhea was similar in the unblinded external control and in the blinded study groups combined (20.9% vs. 20.2% respectively; P=0.91). There was no difference in the duration of diarrhea, maximum number of bowel movements or prolonged admission because of diarrhea among the groups. All-cause mortality did not differ between groups. The combined probiotic strains LA-5, BB-12, and LC-01 do not have an effect in the prevention of AAD in hospitalized patients.

The Ser/Thr Kinase PrkC Participates in Cell Wall Homeostasis and Antimicrobial Resistance in Clostridium difficile.

Clostridium difficile is the leading cause of antibiotic-associated diarrhea in adults. During infection, C. difficile must detect the host environment and induce an appropriate survival strategy. Signal transduction networks involving serine/threonine kinases (STKs) play key roles in adaptation, as they regulate numerous physiological processes. PrkC of C. difficile is an STK with two PASTA domains. We showed that PrkC is membrane associated and is found at the septum. We observed that deletion of prkC affects cell morphology with an increase in mean size, cell length heterogeneity, and presence of abnormal septa. A ΔprkC mutant was able to sporulate and germinate but was less motile and formed more biofilm than the wild-type strain. Moreover, a ΔprkC mutant was more sensitive to antimicrobial compounds that target the cell envelope, such as the secondary bile salt deoxycholate, cephalosporins, cationic antimicrobial peptides, and lysozyme. This increased susceptibility was not associated with differences in peptidoglycan or polysaccharide II composition. However, the ΔprkC mutant had less peptidoglycan and released more polysaccharide II into the supernatant. A proteomic analysis showed that the majority of C. difficile proteins associated with the cell wall were less abundant in the ΔprkC mutant than the wild-type strain. Finally, in a hamster model of infection, the ΔprkC mutant had a colonization delay that did not significantly affect overall virulence.

Clostridium difficile infections in geriatric patients

Clostridium difficile is the main cause of nosocomial antibiotic-associated diarrhea in adults in Europe and North America. Infections with C. difficile typically occur in elderly patients with comorbidities and prior antibiotic therapy. Other risk factors are proton pump inhibitors, which are taken by many elderly patients. The main virulence factors are toxinsA andB. The clinical spectrum ranges from asymptomatic colonization to severe disease with abdominal complications and sepsis. The current diagnostic gold standard is anaerobic culture but is impractical in routine use due to the long duration. Proven techniques involve glutamate dehydrogenase, toxinsA and B immunoassays and PCR. First infections and recurrences can be treated with 400-500mg metronidazole 3 times aday for 10days. Further recurrences, serious infections or patients with more than two positive predictors should be treated orally with 125mg vancomycin 4 times aday for at least 10days. Fidaxomicin, rifaximin, stool transplantation and monoclonal antibodies are promising alternative therapies.

Probiotics Reduce the Risk of Antibiotic-Associated Diarrhea in Adults (18-64 Years) but Not the Elderly (>65 Years): A Meta-Analysis.

Antibiotic-associated diarrhea (AAD) is a common problem in adults and elderly patients due to the widespread use of antibiotics in this population. Multiple previous systematic reviews have demonstrated an association between specific probiotics and decrease of AAD, especially in children. As there is no specific analysis concerning the elderly patients, we decided to focus on adults, especially elderly people. We performed a systematic review of the literature regarding the use of probiotics in the treatment of AAD in adults (18-64 years old) and elderly subjects (≥65 years old). We identified 436 articles that met the search criteria. Thirty randomized controlled trials met the predefined inclusion criteria and were included in the meta-analysis. There was considerable heterogeneity among the trials (P < .001); thus, subgroup analyses were performed. The meta-analysis resulted in a pooled relative risk (RR) of AAD of 0.69 (95% confidence interval [95% CI]: 0.62-0.76) in a fixed effects model and 0.58 (95% CI: 0.48-0.71) in a random effects model, as compared with placebo. The positive association between intake of probiotic and reduced risk of AAD was observed in adults (RR, 0.47; 95% CI: 0.4-0.56). In contrast, in elderly patients, there was no positive effect (RR, 0.94; 95% CI: 0.76-1.15) of probiotic use and AAD. In summary, the results emerging from our meta-analysis suggested that adjunct probiotic administration is associated with a reduced risk of AAD in adults but not in elderly people.

Clostridium difficile isolation in children hospitalized with diarrhoea

Abstract Introduction Clostridium difficile is the leading cause of nosocomial and antibiotic-associated diarrhoea in adults, and its incidence has substantially risen over the last few years. The prevalence of this infection in children is difficult to assess due to the high rates of colonisation in this setting. Materials and methods A one-year retrospective study was conducted on children under 15 years admitted to hospital with acute diarrhoea. Epidemiological, clinical, laboratory findings and outcome of children with Clostridium difficile infection (CDI) were compared to other causes of diarrhoea. Risk factors for CDI were identified by multivariate analysis. Results Two hundred and fifty children with acute diarrhoea were identified. A microbiological pathogen was identified in 79 (45.4%) of 174 patients who underwent complete testing: 19 CDI (25.6%, 13 of which were enterotoxin-producing), 21 other bacteria (28.6%), and 34 viruses (45.8%; rotavirus n = 31; adenovirus n = 3). The estimated incidence of CDI was 3 cases/1000 admissions, with 68.4% of them occurring in children younger than 2 years. Overall, 15.8% were community-acquired. Compared to other causes of diarrhoea, CDI was associated with comorbidity (P Conclusions The isolation of Clostridium difficile is common in hospitalized children with diarrhoea in our setting. CDI is more frequent in children with comorbidity and recent contact with the health-care system, presenting a mostly oligosymptomatic clinical course. Further studies are needed to understand the epidemiology of this infection in paediatrics, especially the percentage of asymptomatic carriers.

Co-infection as a confounder for the role of Clostridium difficile infection in children with diarrhoea: a summary of the literature.

Although Clostridium difficile is a major cause of antibiotic-associated diarrhoea in adults, the incidence and severity of C. difficile infection (CDI) in children is unclear. One complicating factor in assessing the role of CDI in children is the possibility of co-infection with other gastrointestinal pathogens. In this review, we summarise the literature concerning C. difficile co-infections in young children, in an attempt to discuss the rate of co-infections and their potential role in the severity of CDI clinical presentation. We identified 31 studies where co-infections were analysed, comprising 1,718 patients with positive C. difficile tests. The pooled percentage of reported co-infections was 20.7% (range 0-100%). Viral co-infections were most commonly reported (46%), with bacteria and parasites accounting for 14.9% and 0.01% of cases, respectively. However, the panel of co-infections tested for varied considerably among studies and 38% of stated co-infections did not have a pathogen reported. Substantial variation in how and when tests for gastrointestinal co-infections are carried out, small sample sizes and a lack of clear CDI case definitions preclude meaningful conclusions on the true rate of co-infections in this patient population. This review suggests that co-infections may be common in children with diarrhoea who tested positive for C. difficile. Given a lack of CDI case definitions, especially in young children under the age of 5 years, a broad panel of pathogens should be tested for to exclude other microbiological causes. However, the summarised poor quality of the available literature on this subject highlights a need for further studies.

Aislamiento de Clostridium difficile en niños hospitalizados con diarrea

IntroductionClostridium difficile is the leading cause of nosocomial and antibiotic-associated diarrhea in adults, and its incidence has substantially risen over the last few years. The prevalence of this infection in children is difficult to assess due to the high rates of colonization in this setting. Material and methodsA one-year retrospective study was conducted on children under 15 years admitted to hospital with acute diarrhea. Epidemiological, clinical, laboratory findings and outcome of children with Clostridium difficile infection (CDI) were compared to other causes of diarrhea. Risk factors for CDI were identified by multivariate analysis. ResultsTwo hundred and fifty children with acute diarrhea were identified. A microbiological pathogen was identified in 79 (45.4%) of 174 patients who underwent complete testing: 19 CDI (25.6%, 13 of which were enterotoxin-producing), 21 other bacteria (28.6%), and 34 viruses (45.8%; rotavirus n=31; adenovirus n=3). The estimated incidence of CDI was 3 cases/1,000 admissions, with 68.4% of them occurring in children younger than 2 years. Overall, 15.8% were community-acquired. Compared to other causes of diarrhea, CDI was associated with comorbidity (P<.0001), recent contact with the health-care system (P<.0001) or intensive care unit stay (P=.003) and exposure to antibiotics in the previous month (P<.0001). The clinical course of children with CDI was less symptomatic. There were no clinical differences between Clostridium difficile toxin-producers and non-toxin producers. Comorbidity was identified as the main risk factor associated with CDI (OR 40.02, 95% CI 6.84-232.32; P<.0001). ConclusionsThe isolation of Clostridium difficile is common in hospitalized children with diarrhea in our setting. CDI is more frequent in children with comorbidity and recent contact with the health-care system, presenting a mostly oligosymptomatic clinical course. Further studies are needed to understand the epidemiology of this infection in pediatrics, especially the percentage of asymptomatic carriers.

Controversies Surrounding Clostridium difficile Infection in Infants and Young Children.

Clostridium difficile is a frequent cause of antibiotic-associated diarrhea in adults and older children. However, as many as 80% of infants can be asymptomatically colonized. The reasons for this have not been well established but are believed to be due to differences in toxin receptors or toxin internalization. Determining which children who test positive for C. difficile warrant treatment is exceedingly difficult, especially in the setting of increased rates of detection and the rising risk of disease in children lacking classic risk factors for C. difficile.

Probiotics in the Mechanism of Protection Against Gut Inflammation and Therapy of Gastrointestinal Disorders

A growing body of experimental and clinical evidence supports the hypothesis that the intestinal microbiota markedly influences function and the structure of the mucosal lining. Intestinal microbiota can potentially cause damage to the mucosa either directly by releasing toxins or indirectly by causing a detrimental immune response. Probiotic bacteria have been defined as live microorganisms, which when consumed in adequate amounts, confer a health benefit for the host. In recent years, the therapeutic and preventive application of probiotics for several gastrointestinal and liver disorders has received increasing attention. Probiotics appear to be beneficial for premature infants who suffer necrotizing enterocolitis. The effectiveness of certain probiotics as treatment for infectious and antibioticassociated diarrhea in adults and for allergic disorders in children has been supported by clinical studies; however, the potential mechanism( s) remains to be studied. Experimental studies and clinical trials for probiotic treatment of inflammatory bowel diseases (IBD) have yielded conflicting results. Daily intake of selected probiotics was effective in the prevention of ulcerative colitis and the attenuation of the active onset of Crohn's disease or ulcerative colitis but others failed to show a beneficial effect. The combination of Lactobacillus, Bifidobacterium, Saccharomyces boulardi and the treatment with Escherichia coli Nissle were found beneficial in inducing and maintaining remission of disease activity of gut inflammation and moderately severe ulcerative colitis. Probiotic bacteria were considered in some studies as a safe adjuvant when added to triple eradication therapy against the symptoms induced by the major gastric pathogen, Helicobacter pylori. This review attempted to overview these new exciting advances in the role of these microbes in the pathogenesis, management and treatment of gastrointestinal disorders.

Effect of ProbioticLactobacillus(Lacidofil® Cap) for the Prevention of Antibiotic-associated Diarrhea: A Prospective, Randomized, Double-blind, Multicenter Study

Antibiotic-associated diarrhea (AAD) is a common complication of antibiotic use. There is growing interest in probiotics for the treatment of AAD and Clostridium difficile infection because of the wide availability of probiotics. The aim of this multicenter, randomized, placebo-controlled, double-blind trial was to assess the efficacy of probiotic Lactobacillus (Lacidofil® cap) for the prevention of AAD in adults. From September 2008 to November 2009, a total of 214 patients with respiratory tract infection who had begun receiving antibiotics were randomized to receive Lactobacillus (Lacidofil® cap) or placebo for 14 days. Patients recorded bowel frequency and stool consistency daily for 14 days. The primary outcome was the proportion of patients who developed AAD within 14 days of enrollment. AAD developed in 4 (3.9%) of 103 patients in the Lactobacillus group and in 8 (7.2%) of 111 patients in the placebo group (P=0.44). However, the Lactobacillus group showed lower change in bowel frequency and consistency (50/103, 48.5%) than the placebo group (35/111, 31.5%) (P=0.01). Although the Lacidofil® cap does not reduce the rate of occurrence of AAD in adult patients with respiratory tract infection who have taken antibiotics, the Lactobacillus group maintains their bowel habits to a greater extent than the placebo group.

Epidemiological Features of Clostridium difficile-Associated Disease Among Inpatients at Children's Hospitals in the United States, 2001–2006

Clostridium difficile is the main cause of nosocomial and antibiotic-associated diarrhea in adults. Recently, the incidence and severity of C difficile-associated disease in adults have been increasing. Whether similar phenomena are occurring among children remains unknown. Our study describes the epidemiological features of C difficile-associated disease in hospitalized children. We conducted a retrospective cohort study of hospitalized children with C difficile-associated disease at 22 freestanding children's hospitals in the United States, from 2001 to 2006. Cases of C difficile-associated disease were defined as a hospitalized child with a discharge code for C difficile infection, a laboratory billing charge for a C difficile toxin assay, and receipt of antimicrobial therapy for C difficile-associated disease. We identified 4895 patients with C difficile-associated disease. Over the study period, the annual incidence of C difficile-associated disease increased from 2.6 to 4.0 cases per 1000 admissions and from 4.4 to 6.5 cases per 10 000 patient-days. The median age of children with C difficile-associated disease was 4 years. Twenty-six percent of patients were <1 year of age. The majority of patients (67%) had underlying chronic medical conditions. The colectomy and all-cause mortality rates among children with C difficile-associated disease did not increase during the study period. The annual incidence of C difficile-associated disease in hospitalized children increased significantly from 2001 to 2006. However, the rates of colectomy and in-hospital death have not increased in children with C difficile-associated disease as they have among adults. The risk factors and outcomes for children with C difficile-associated disease remain to be defined in future studies.