Cases Of Antibiotic-associated Diarrhea Research Articles

Prevention of antibiotic-associated diarrhoea by a fermented probiotic milk drink

To study the preventive effect of a milk drink fermented with multistrain probiotics on antibiotic associated diarrhoea (AAD). Double-blind placebo controlled study. University Hospital of North Norway. Of 853 patients treated with antibiotics, 87 met the inclusion criteria, and were randomized to ingestion of a fermented milk drink containing LGG, La-5 and Bb-12 (n=46) or placebo with heat-killed bacteria (n=41), during a period of 14 days. A diary was recorded, and stool samples were collected for microbiological analyses. Sixty-three patients completed the study according to the protocol; two patients (5.9%) in the treatment group and eight (27.6%) in the placebo group developed AAD (P=0.035). The relative risk of developing AAD was 0.21 (95% confidence interval: 0.05-0.93) when given probiotic milk drink. A fermented multistrain probiotic milk drink may prevent four of five cases of AAD in adult hospitalized patients. TINE BA, Oslo, Norway.

Surface layer proteins from Clostridium difficile induce inflammatory and regulatory cytokines in human monocytes and dendritic cells

Clostridium difficile, an etiological agent of most cases of antibiotic-associated diarrhea, exerts its pathological action mainly by the activity of toxin A and toxin B. Less known is the role that S-layer proteins (SLPs), predominant surface components of the bacterium, may play in pathogenesis. Here, we evaluate the ability of SLPs to modulate the function of human monocytes and dendritic cells (DC) and to induce inflammatory and regulatory cytokines, influencing the natural and adaptive immune response. To this aim, SLPs were extracted from the clinical isolate C253 and characterized for their effects on immune cells. SLPs induced the release of elevated amounts of interleukin (IL)-1β and IL-6 pro-inflammatory cytokines by resting monocytes, induced maturation of human monocyte-derived DC (MDDC), and enhanced proliferation of allogeneic T cells. C253-SLP-treated MDDC also secreted large amounts of IL-10 and IL-12p70 and induced a mixed Th1/Th2 orientation of immune response in naïve CD4 T cells. In conclusion, C. difficile SLPs may contribute to the pathogenicity of the bacterium by perturbing the fine balance of inflammatory and regulatory cytokines. These data are of interest also in the light of the possible use of SLPs in a multicomponent vaccine against C. difficile infections for high-risk patients.

Die Antibiotika-assoziierte Diarrhö

The incidence of antibiotic-associated diarrhea (AAD) differs with the antibiotic and varies from 15 - 25 %. Most cases of AAD are directly or indirectly caused by alterations of gut microflora by the antibiotics resulting in clinically mild AAD cases due to functional disturbances of intestinal carbohydrate or bile acid metabolism. Alternatively, changes in the gut flora allow pathogens to proliferate. Clostridium difficile is responsible for 10 - 15 % of all cases of AAD and almost of all cases of antibiotic-associated pseudomembraneous colitis. There is also a growing body of evidence which supports the responsibility of Klebsiella oxytoca for the development of antibiotic-associated hemorrhagic colitis. Diagnosing Clostridium difficile-associated diarrhea should be based both on fecal-cytotoxin detection and culture. With respect to specific therapy, metronidazol has become the first choice whereas treatment with oral vancomycin should be reserved for patients who have contraindications or intolerance to or who have failed to respond to metronidazole. Probiotics such as Sacharomyces boulardii can reduce the risk of development. Restrictive antibiotic policies (e. g. restricting clindamycin and cephalosporins) and the implementation of a comprehensive hospital infection control have also been shown to be effective in reducing the incidence of AAD.

Diarrhées associées aux antibiotiques chez le sujet âgé

Purpose. – Most of the antibiotic-associated diarrhea (AAD) cases result from a transient disturbance in the function of the normal intestinal flora and are spontaneously solved when discontinuing the antibacterial therapy. However, a mild diarrhea lasting several days may induce a dehydration or worsen a denutrition in frail elderly people. Current knowledge and key points. – The incidence of AAD varies between 5 and 25% depending on the concerned antibiotic. Only 10–20% of all AAD cases are caused by infection, especially with Clostridium difficile, for which advanced age is a major risk factor. The first biological exam to perform when severe AAD or in frail people is the detection of C. difficile toxins, especially in elderly patient treated with beta-lactam antibiotics. Nevertheless, other infectious organisms causing AAD may be considered, as Staphylococcus aureus when predominant in stool cultures from patients treated with fluoroquinolones or as Klebsiella oxytoca when isolated in bloody diarrhea from patients treated with ampicillin. Elevated fecal counts of Candida spp. found in patients treated with antibiotics is rather the consequence of therapy than the cause of AAD. The prevention of AAD is based on a rational antibiotic use to avoid endogenous selection of C. difficile and on the improvement of the hygiene measures to limit the exogenous transmission of the bacteria or related spores by spoiled hands. Future prospects. – Simultaneous prescription of non-pathogenic living organisms, capable of re-establishing the equilibrium of the intestinal flora, should be better described, especially in elderly people, because of its important economic impact.

Genotyping of enterotoxigenic Clostridium perfringens fecal isolates associated with antibiotic-associated diarrhea and food poisoning in North America.

Clostridium perfringens type A isolates producing enterotoxin (CPE) are an important cause of food poisoning and non-food-borne human gastrointestinal (GI) diseases, including antibiotic-associated diarrhea (AAD). Recent studies suggest that C. perfringens type A food poisoning is caused by C. perfringens isolates carrying a chromosomal cpe gene, while CPE-associated non-food-borne GI diseases, such as AAD, are caused by plasmid cpe isolates. Those putative relationships, obtained predominantly with European isolates, were tested in the current study by examining 34 cpe-positive, C. perfringens fecal isolates from North American cases of food poisoning or AAD. These North American disease isolates were all classified as type A using a multiplex PCR assay. Furthermore, restriction fragment length polymorphism and pulsed-field gel electrophoresis genotyping analyses showed the North American AAD isolates included in this collection all have a plasmid cpe gene, but the North American food poisoning isolates all carry a chromosomal cpe gene. Western blotting demonstrated CPE expression by nearly all of these disease isolates, confirming their virulence potential. These findings with North American isolates provide important new evidence that, regardless of geographic origin or date of isolation, plasmid cpe isolates cause most CPE-associated AAD cases and chromosomal cpe isolates cause most C. perfringens type A food poisoning cases. These findings hold importance for the development of assays for distinguishing cases of CPE-associated food-borne and non-food-borne human GI illnesses and also identify potential epidemiologic tools for determining the reservoirs for these illnesses.

Antimicrobial activities of synthetic bismuth compounds against Clostridium difficile.

Clostridium difficile is a major nosocomial pathogen responsible for pseudomembranous colitis and many cases of antibiotic-associated diarrhea. Because of potential relapse of disease with current antimicrobial therapy protocols, there is a need for additional and/or alternative antimicrobial agents for the treatment of disease caused by C. difficile. We have synthesized a systematic series of 14 structurally simple bismuth compounds and assessed their biological activities against C. difficile and four other gastrointestinal species, including Helicobacter pylori. Here, we report on the activities of six compounds that exhibit antibacterial activities against C. difficile, and some of the compounds have MICs of less than 1 microgram/ml. Also tested, for comparison, were the activities of bismuth subcitrate and ranitidine bismuth citrate obtained from commercial sources. C. difficile and H. pylori were more sensitive both to the synthetic bismuth compounds and to the commercial products than were Escherichia coli, Pseudomonas aeruginosa, and Proteus mirabilis, and the last three species were markedly resistant to the commercial bismuth salts. Testing with human foreskin fibroblast cells revealed that some of the synthetic compounds were more cytotoxic than others. Killing curves for C. difficile treated with the more active compounds revealed rapid death, and electron microscopy showed that the bismuth of these compounds was rapidly incorporated by C. difficile. Energy dispersive spectroscopy X-ray microanalysis of C. difficile cells containing electron-dense material confirmed the presence of internalized bismuth. Internalized bismuth was not observed in C. difficile treated with synthetic bismuth compounds that lacked antimicrobial activity, which suggests that the uptake of the metal is required for killing activity. The nature of the carrier would seem to determine whether bismuth is transported into susceptible bacteria like C. difficile.

Rapid detection of toxigenic Clostridium difficile from stool samples by a nested PCR of toxin B gene

Toxigenic Clostridium difficile is the aetiologic agent of most cases of antibiotic-associated diarrhoea and pseudomembranous colitis. The present standard method for C. difficile diagnosis is a cytotoxicity assay, performed on human fibroblast cultures. It is time consuming and requires special facilities. A nested-PCR assay detecting toxin B gene within a few hours was designed. One hundred and two stool samples were collected during four months. All samples were processed for toxin B-PCR, cultured for C. difficile and tested for cytotoxicity. This approach achieved 99% concordance with the cytotoxic assay. The sensitivity and specificity for the new PCR assay were 96·3% and 100% respectively. The procedure described is easy to perform, does not require special equipment and had produced excellent results. It deserves serious consideration for routine clinical microbiology laboratory use.

Mechanisms and management of antibiotic-associated diarrhea.

Only 10%-20% of all cases of antibiotic-associated diarrhea (AAD) are caused by infection with Clostridium difficile. Other infectious organisms causing AAD include Clostridium perfringens, Staphylococcus aureus, Klebsiella oxytoca, Candida species, and Salmonella species. Most of the clinically mild AAD cases are due to functional disturbances of intestinal carbohydrate or bile acid metabolism, to allergic and toxic effects of antibiotics on intestinal mucosa, or to pharmacological effects on motility. Saccharomyces boulardii and Enterococcus SF68 can reduce the risk of developing AAD. Patients receiving antibiotic treatment should avoid food containing high amounts of poorly absorbable carbohydrates. Mild cases of AAD that may or may not be caused by C. difficile can be resolved by discontinuation of antibiotic therapy and by dietary carbohydrate reduction. Only severe AAD caused by C. difficile requires specific antibiotic treatment.

Management of Clostridium difficile infection and other antibiotic-associated diarrhoeas.

Most cases of antibiotic-associated diarrhoea are due to Clostridium difficile or are enigmatic. Patients with C. difficile-associated disease are more likely to have colitis, severe disease and nosocomial acquisition. The preferred diagnostic test is a C. difficile toxin assay using a tissue culture assay or enzyme immunoassay. The usual treatment is withdrawal of the inducing agent, sometimes supplemented with oral vancomycin or metronidazole. Response rates approach 100%; the major complication is relapse. Major complications include toxic megacolon, devastating diarrhoea, pseudomembranous colitis and hypoalbuminemia. Antibiotic-associated diarrhoea with negative tests for C. difficile toxin is usually dose-related and responds to antibiotic withdrawal.

Antibiotic-induced diarrhea

Diarrhea is a common complication of antibiotic therapy and can range from mild soiling of a cast to severe and life-threatening pseudomembranous colitis. Although clindamycin is the most notorious, almost all antibiotics, particularly penicillins and cephalosporins, may also be responsible (Bartlett, 1992; Kelly, Pothoulakis, & LaMont, 1994). Because of the frequent use of these antibiotics in orthopaedic patients, antibiotic-associated enteric disease is a common problem in this population. About 15% to 25% of cases of antibiotic-associated diarrhea are caused by Clostridium difficile (Bartlett, 1992; George, 1984; Kelly et al., 1994). The majority of patients with antibiotic-associated diarrhea have no identifiable etiologic agent. Salmonella, enterotoxin-producing Clostridium perfringens (Borriello et al., 1984) and Candida albicans (Danna et al., 1991) have rarely been identified as causative agents. This article describes the role of C. difficile as an enteric pathogen and its spectrum of clinical disease, including diagnosis, treatment, and prevention of nosocomial transmission.

Antibiotic-Induced Diarrhea

Diarrhea is a common complication of antibiotic therapy and can range from mild soiling of a cast to severe and life-threatening pseudomembranous colitis. Although clindamycin is the most notorious, almost all antibiotics, particularly penicillins and cephalosporins, may also be responsible (Bartlett, 1992; Kelly, Pothoulakis, & LaMont, 1994). Because of the frequent use of these antibiotics in orthopaedic patients, antibiotic-associated enteric disease is a common problem in this population. About 15% to 25% of cases of antibiotic-associated diarrhea are caused by Clostridium difficile (Bartlett, 1992; George, 1984; Kelly et al., 1994). The majority of patients with antibiotic-associated diarrhea have no identifiable etiologic agent. Salmonella, enterotoxin-producing Clostridium perfringens (Borriello et al., 1984) and Candida albicans (Danna et al., 1991) have rarely been identified as causative agents. This article describes the role of C. difficile as an enteric pathogen and its spectrum of clinical disease, including diagnosis, treatment, and prevention of nosocomial transmission.

Medical treatment of Clostridium difficile-related gastrointestinal infection - whither vancomycin?

One of the major advances in anaerobic microbiology in the past few decades has been clarifing the causal relationship between Clostridium difficile and pseudomembranous colitis, and its association with previous antimicrobial therapy. It is now clear that C. difficile is responsible for virtually all cases of pseudomembranous colitis and up to 20% of cases of antibiotic-associated diarrhoea. Clindamycin is widely recognised for its propensity to induce these diseases, but broad-spectrum penicillins and cephalosporins (reflecting their widespread usage) are much more common precipitating agents.

Antibiotic-associated diarrhea.

Diarrhea is clearly one of the most common side effects encountered with antimicrobial treatment. Virtually all drugs with an antibacterial spectrum of activity have been implicated, although there are definite differences in associated incidence rates that appear to depend on spectrum of activity and pharmacokinetic properties. Most cases of antibiotic-associated diarrhea can be classified in two categories: cases in which Clostridium difficile is implicated and cases in which no putative agent or recognized pathophysiological mechanism is clearly established. This review is intended to provide management guidelines for patients with diarrhea that occurs in association with antibacterial agents.

Application of a technique for serogrouping Clostridium difficite in an outbreak of antibiotic-associated diarrhoea

A severe outbreak of Clostridium difficile antibiotic-associated diarrhoea (AAD) in an orthopaedic surgical unit is reported. Thirty-seven cases and eight relapses were observed. The 45 related strains together with another 13 strains of C. difficile isolated during the same period in other wards of the same hospital were typed by detection of cytotoxin production, determination of sorbitol fermentation and serogrouping by agglutination with six rabbit antisera defining the serogroups A, B, C, D, F and G. All the strains from the outbreak belonged to serogroup C, were toxigenic and fermented sorbitol. In contrast, four different patterns were observed in seven isolates from cases of AAD in other wards. Finally, six strains isolated from four asymptomatic adults, one adult suffering from shigellosis and one child with salmonellosis demonstrated two patterns different from that of the epidemic isolates. The data strongly suggest nosocomial spread of this micro-organism.

Antibiotic‐associated diarrhoea and methicillin‐resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus was thought to be the cause of 10 cases of antibiotic-associated diarrhoea observed over a 12-month period at The Royal Melbourne Hospital. Each patient had significant underlying disease, and all had been treated with multiple, broad-spectrum antibiotic agents. The diagnosis was made on the distinctive Gram-stain appearance of faecal smears, the heavy predominant growth of methicillin-resistant Staph. aureus from stool cultures, and the absence of other bowel pathogens, including toxigenic Clostridium difficile. Diarrhoea usually responded to treatment with vancomycin or bacitracin, and, in patients whose condition improved, the stools cleared of staphylococci. Patients with staphylococcal diarrhoea present a significant crossinfection risk, and early diagnosis, treatment, and isolation are essential.