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PubMed2006

Comparative analysis of prevalence, risk factors, and molecular epidemiology of antibiotic-associated diarrhea due to Clostridium difficile, Clostridium perfringens, and Staphylococcus aureus.

We prospectively studied the comparative epidemiology and risk factors for Clostridium difficile, Clostridium perfringens, and Staphylococcus aureus antibiotic-associated diarrhea (AAD). Four thousand six hundred fifty-nine inpatient fecal specimens (11 months) were tested for C. difficile cytotoxin, C. perfringens enterotoxin, and S. aureus by Vero cell assay, enzyme-linked immunosorbent assay, and growth on fresh blood agar, respectively. Two distinct age-, sex-, and location-matched control patient groups were used for multivariate logistic regression risk factor analyses: symptomatic patients who were AAD pathogen negative and asymptomatic patients with histories of recent antimicrobial therapy. All AAD pathogen isolates were DNA fingerprinted. In AAD cases, the prevalences of C. difficile cytotoxin, C. perfringens enterotoxin, and S. aureus were 12.7%, 3.3%, and 0.2%, respectively (15.8% overall). Age of >70 years was a common risk factor. Other risk factors for infective AAD and C. difficile AAD included length of hospital stay and use of feeding tubes (length of stay odds ratios [OR], 1.017 and 1.012; feeding tube OR, 1.864 and 2.808). Female gender and use of antacids were significantly associated with increased risk of C. perfringens AAD (OR, 2.08 and 2.789, respectively), but unlike what was found for C. difficile AAD, specific antibiotic classes were not associated with increased risk. A limited number of genotypes caused the majority of C. difficile and C. perfringens AAD cases. Similar to what was found for C. difficile AAD, there was epidemiological evidence of C. perfringens AAD case clustering and reinfection due to different strains. C. difficile AAD was approximately 4 and 60 times more common than C. perfringens AAD and S. aureus AAD, respectively. Risk factors for these AAD pathogens differed, highlighting the need to define specific control measures. There is evidence of nosocomial transmission in cases of C. perfringens AAD.

Adolescent↗
PubMed2003

Comparative in vitro activity of PH-027 versus linezolid and other anti-anaerobic antimicrobials against clinical isolates of Clostridium difficile and other anaerobic bacteria.

PH-027 is a new 5-triazole oxazolidinone synthesized in our laboratories, which shows strong activity against gram-positive aerobic bacteria including clinical isolates. The objective of this study was to investigate the in vitro activity of this compound in comparison with linezolid and other antibiotics against gram-positive and gram-negative anaerobes. The in vitro activity of PH-027 in comparison with those of linezolid and other antimicrobial agents was evaluated against 201 clinical isolates of gram-positive and gram-negative anaerobic bacteria by agar dilution and Etest methods. PH-027 showed excellent activity, with minimum inhibitory concentrations (MIC) in the range of 0.12-4.0 microg/ml against all isolates; MIC90s being 4.0, 1.0, 2.0, 2.0 and 2.0 microg/ml against Clostridium difficile, Peptostreptococcus spp., Bacteroides fragilis, Prevotella bivia and Fusobacterium spp. respectively. In comparison, linezolid had MIC in the range of 0.5-4.0 microg/ml against all isolates, with MIC90s of 2.0, 4.0, 4.0, 4.0 and 2.0 microg/ml against the same set of bacteria respectively. PH-027 demonstrated excellent in vitro activity that is superior to linezolid against Peptostreptococcus spp., B. fragilis and P. bivia. However, against C. difficile and Fusobacterium spp, PH-027 and linezolid showed comparable in vitro activity. Against all anaerobes, metronidazole, PH-027 and, to a lesser extent, linezolid had the most potent activity. From the results of in vitro susceptibility testing, both linezolid and PH-027 show promise in the treatment of anaerobic infections.

Acetamides↗
PubMedDate not supplied

The clinical significance of antibiotic-associated pseudomembranous colitis in the 1990s.

Antibiotic-associated pseudomembranous colitis is an uncommon but potentially serious adverse reaction, resulting in acute diarrhoea and characterised by colonic pseudomembranes. A direct relationship between the disease, recent antibiotic therapy and proliferation of Clostridium difficile in the colonic lumen was established in the late 1970s. It is thought that antibiotic therapy may alter the enteric flora, enabling C. difficile to proliferate and produce toxins with cytopathic (toxin B or cytotoxin) and hypersecretory (toxin A or enterotoxin) effects on the mucosa. Apart from clindamycin, the first antibiotic recognised to be clearly associated with pseudomembranous colitis, the antimicrobial agents most commonly responsible are cephalosporins and ampicillin (or amoxicillin). However, virtually all antibiotics except parenterally administered aminoglycosides can cause the disease. Vancomycin and metronidazole, 2 drugs used to treat antibiotic-associated pseudomembranous colitis, have also been reported to be responsible for the complication when used parenterally. Pseudomembranous colitis may develop after perioperative prophylactic antibiotic therapy with cephalosporins. Antibiotic-associated pseudomembranous colitis is most frequent in elderly and debilitated patients and in intensive care units. Nosocomial acquisition of C. difficile has been documented. Therefore it has been recommended that enteric isolation precautions should be taken with patients with this disease. The clinical symptoms include watery diarrhoea, abdominal cramping, and frequently fever, leucocytosis and hypoalbuminaemia. Toxic megacolon and acute peritonitis secondary to perforation of the colon are the most serious complications. The pseudomembranes are usually seen during endoscopic procedures, sigmoidoscopy or, if possible, colonoscopy; the most useful microbiological tests for confirmation of the diagnosis include cycloserine cefoxitin fructose agar (CCFA) stool cultures and stool toxin assays on tissues or by immunological techniques. However, cultures and toxin tests may be positive in patients without pseudomembranous colitis or C. difficile-associated diarrhoea. Mild cases may respond to discontinuation of the drug responsible, but therapy with an anticlostridial antibiotic is often necessary: a 10-day course of oral vancomycin, metronidazole or bacitracin should be given. Relapses are seen in 5 to 50% of patients treated. Antibiotic treatment should avoid sporulation leading to other relapses. 'Biotherapy' (lactobacilli, Saccharomyces) has also been proposed.

Anti-Bacterial Agents↗
PubMedDate not supplied

Acute appendicitis: the role of enterotoxigenic strains of Bacteroides fragilis and Clostridium difficile.

BACKGROUND: The aim of this study was to investigate whether there is a relationship between enterotoxin-producing B. fragilis strains and toxigenic C. difficile strains and the pathogenesis of acute appendicitis. MATERIAL AND METHODS: Post-appendectomy tissues from 34 patients with histopathologically confirmed phlegmonous or gangrenous appendicitis were studied. RESULTS: Among 86 anaerobes isolated, the B. fragilis group was most frequently isolated: 34 B. fragilis strains were cultured from 21 post-appendectomy tissues. Two enterotoxin-producing B. fragilis strains were found. Enterotoxin titers (1:10 and 1:160, respectively) were measured on HT29/C cells. The presence of the enterotoxin gene was confirmed by PCR in DNA extracted from both strains. Among 21 DNA samples isolated from those post-appendectomy tissues from which B. fragilis strains were cultured, the presence of the enterotoxin gene was confirmed in only one case (the corresponding B. fragilis strain enterotoxin titer was 1:160). A unique toxigenic C. difficile strain was also cultured from the tissue of an adult patient with gangrenous non-perforated appendicitis. The presence of toxin A and toxin B genes was confirmed by PCR in DNA extracted from the C. difficile strain, but these genes were not found in the DNA extracted from the corresponding tissue. CONCLUSION: The presence of enterotoxigenic B. fragilis and toxigenic C. difficile strains was shown in post-appendectomy tissue from patients with phlegmonous and gangrenous appendicitis, and the B. fragilis enterotoxin gene was detected directly in the corresponding tissue. Further investigations (including immunologic aspects) require to confirm the role of these toxins in pathogenesis of acute appendicitis.

Adult↗
PubMed2006

[Therapeutic possibilities of probiotics in antibiotic-related diarrhea].

One of the major problems associated with the use of antibiotics is the occurrence of antibiotic-related diarrhea. Although most such cases of diarrhea are harmless, in individual cases it may lead on to fulminant colitis. In 10-20% of the patients, the causal factor is infection with Clostridium difficile, which multiplies unhindered in patients on antibiotics. In the meantime, controlled, randomized studies have shown that probiotics can exercise a preventive effect in antibiotic-related diarrhea. The administration of Saccharomyces boulardii or Lactobacillus rhamnosus GG reduces the relative risk of an antibiotic-related diarrhea developing by 0.5. The data are more uniform in children than in adults.

Adult↗
PubMed1999

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 has produced excellent results. It deserves serious consideration for routine clinical microbiology laboratory use.

Bacterial Toxins↗
PubMed2005

An improved protocol for pulsed-field gel electrophoresis typing of Clostridium difficile.

Pulsed-field gel electrophoresis (PFGE) is the 'gold standard' technique for bacterial typing and has proved to be discriminatory and reproducible for typing Clostridium difficile. Nevertheless, a high proportion of strains are non-typable by this technique due to the degradation of the DNA during the process. The introduction of several modifications in the PFGE standard procedure increased typability from 40% (90 isolates) to 100% (220 isolates) while maintaining the high degree of discrimination and reproducibility of the technique.

Bacterial Typing Techniques↗
PubMed1991

Evaluation of the proposed interaction of nucleic acid with Clostridium difficile toxins A and B and the effects of nucleases on cytotoxicity.

Both DNA and RNA were found to co-purify with Clostridium difficile toxin B but not toxin A. DNAase treatment greatly reduced the cytotoxicity of toxin B but not of toxin A. RNAase had no effect on either toxin. The effects on toxin B were shown to be due to a contaminating protease and could be inhibited by the serine protease inhibitor phenylmethylsulphonyl fluoride.

Animals↗
PubMed2005

A large outbreak of Clostridium difficile-associated disease with an unexpected proportion of deaths and colectomies at a teaching hospital following increased fluoroquinolone use.

BACKGROUND AND OBJECTIVE: Fluoroquinolones have not been frequently implicated as a cause of Clostridium difficile outbreaks. Nosocomial C. difficile infections increased from 2.7 to 6.8 cases per 1000 discharges (P < .001). During the first 2 years of the outbreak, there were 253 nosocomial C. difficile infections; of these, 26 resulted in colectomy and 18 resulted in death. We conducted an investigation of a large C. difficile outbreak in our hospital to identify risk factors and characterize the outbreak. METHODS: A retrospective case-control study of case-patients with C. difficile infection from January 2000 through April 2001 and control-patients matched by date of hospital admission, type of medical service, and length of stay; an analysis of inpatient antibiotic use; and antibiotic susceptibility testing and molecular subtyping of isolates were performed. RESULTS: On logistic regression analysis, clindamycin (odds ratio [OR], 4.8; 95% confidence interval [CI95], 1.9-12.0), ceftriaxone (OR, 5.4; CI95, 1.8-15.8), and levofloxacin (OR, 2.0; CI95, 1.2-3.3) were independently associated with infection. The etiologic fractions for these three agents were 10.0%, 6.7%, and 30.8%, respectively. Fluoroquinolone use increased before the onset of the outbreak (P < .001); 59% of case-patients and 41% of control-patients had received this antibiotic class. The outbreak was polyclonal, although 52% of isolates belonged to two highly related molecular subtypes. CONCLUSIONS: Exposure to levofloxacin was an independent risk factor for C. difficile-associated diarrhea and appeared to contribute substantially to the outbreak. Restricted use of levofloxacin and the other implicated antibiotics may be required to control the outbreak

Anti-Bacterial Agents↗
PubMed2005

Coexistence of multiple PCR-ribotype strains of Clostridium difficile in faecal samples limits epidemiological studies.

Clostridium difficile is an important cause of antibiotic-associated diarrhoea. The simultaneous presence of different strains in individual faecal samples has not yet been established, but is important for epidemiological studies. Recurrences of Clostridium difficile-associated diarrhoea (CDAD) are observed in 15-20 % of patients and have been reported as relapses or reinfections with a new strain. In a period of 1 year, 28 faecal samples from 23 patients with a first episode of CDAD were collected at the Leiden University Medical Centre. In addition, 52 faecal samples from 23 patients, from three different hospitals, with one (n = 19), two (n = 2) or three (n = 2) recurrences were studied. PCR-ribotyping was applied as the standard typing method for the isolates. The toxinogenic and clindamycin-resistance profiles of the isolates was determined by PCR. Of 23 patients with a first episode of CDAD, two (8.7 %) harboured two different types, with no differences in toxinogenicity or clindamycin resistance, within one faecal sample. One of these 23 patients showed two types in three faecal samples from the same episode. Of the 23 patients with recurrences, six (26 %) showed a different strain type isolated in a recurrent episode. The number of cases of multiple C. difficile strains in faecal samples from patients with a first episode of CDAD did not differ significantly from the number of different strains present in recurrent episodes (chi-square test, P < or = 0.2). This observation limits the application of typing methods for studying the epidemiology of CDAD.

Bacterial Toxins↗
PubMed2006

In vitro susceptibility of Clostridium difficile clinical isolates from a multi-institutional outbreak in Southern Québec, Canada.

Clostridium difficile isolates from a 2004 outbreak in Québec, Canada, were all found to be susceptible to metronidazole, vancomycin, rifampin, and meropenem but resistant to bacitracin, cefotaxime, ciprofloxacin, and levofloxacin, and most (>80%) were resistant to ceftriaxone, clarithromycin, gatifloxacin, and moxifloxacin. The predominant NAP1 isolates were susceptible to clindamycin, while the NAP2 isolates were resistant.

Anti-Bacterial Agents↗
PubMed1991

[The problems of rapid diagnosis of Clostridium difficile as causative agent of antibiotic-associated pseudomembranous colitis].

This paper compares three common methods for the detection of Clostridium difficile, i.e. latex agglutination, culture and cytotoxic activity. The sensitivity of the latex agglutination test alone is 70%, of the culture 100% and of the cytotoxin test 66%. Specificities are 93, 96 and 100%, respectively. The latex agglutination has positive and negative predictive values of 58 and 96%; the respective values for the culture are 77 and 100%, for the cytotoxin assay 100 and 96%. Whereas all tests are fairly reliable for the exclusion of diarrhea associated to Clostridium difficile (CAD), the positive predictive values of latex agglutination and culture are too low. If one requests two positive test results for proof of CAD, about two third of all cases are detected by any combination of laboratory tests, while the specificity approaches 100%. We recommend that two of the three tests are performed; the choice is influenced by the possibilities of the laboratory.

Bacterial Proteins↗
PubMed1998

[Choose preparations that affect the intestinal ecosystem as little as possible!].

The administration of antimicrobials often causes ecological disturbances in the normal microflora, such as decreased colonisation resistance which may result in overgrowth of potentially pathogenic micro-organisms such as yeasts and Clostridium difficile. Another possible consequence is the establishment of resistant strains which may spread within the host, or from person to person, causing infection. Resistant bacteria can also transfer resistance genes to their own or other species. The article consists in a review of studies performed by various investigators during the past 20 years, and illustrating the impact of different antimicrobial agents on the human gastrointestinal microflora.

Anti-Bacterial Agents↗
PubMed1994

Clostridium difficile infection: a common clinical problem for the general internist.

Considering the current wide use of antimicrobial agents, the general internist is commonly faced with the patient at risk for diarrhea due to C. difficile. The diagnosis should be considered for any patient with diarrhea who has received any type of antibiotic therapy in the preceding 4-6 weeks. Symptoms may range from a minor bout of diarrhea to fulminant and fatal colitis. Diagnosis usually requires demonstration of the toxin in stool; culture of the organism and fiberoptic endoscopy may play an adjunctive role in selected clinical settings. The ultimate goal in the treatment for C. difficile infection is to repopulate the normal colonic flora in the most efficacious manner. Minimally symptomatic patients may respond to discontinuing the offending antimicrobial agent or using nonspecific binding agents. Oral vancomycin continues to be the "gold standard" for specific treatment, while metronidazole therapy is considered the first-line agent for individuals with milder infection. Oral bacitracin shows promise, though large studies are lacking. Patients with multiple relapses of C. difficile diarrhea can be treated with prolonged courses of vancomycin or a combination of vancomycin and rifampin. Intensive care unit patients who are NPO have few therapeutic options besides intravenous administration of metronidazole and oral administration of vancomycin via clamped nasogastric tube. Preventive efforts are directed at cautious use of antibiotics and the use of vinyl gloves when caring for patients with known infection.

Clostridioides difficile↗
PubMedDate not supplied

The importance of microbiological investigations, medications and artificial feeding in diarrhoea evaluation.

BACKGROUND: Diarrhoea in hospitalised patients is usually attributed to medications especially antibiotics, enteral tube feeding or enteropathogenic bacteria particularly Clostridium difficile. AIMS: The aim of this study was to evaluate the investigations performed on patients who developed diarrhoea during their stay in an acute general hospital. METHOD: Over 18 working days, an unselected group of adult inpatients who developed diarrhoea following their admission to hospital were reviewed. Symptoms, medications, nutritional support and any investigations performed were assessed. RESULTS: Eighty-one patients developed diarrhoea. Forty-nine (60%) were receiving antibiotics prior to the development of symptoms, 30 (37%) were being enterally tube fed, 14 (17%) had positive stool for Clostridium difficile A and B toxin and 3 (4%) had salmonella species positive stool. CONCLUSION: The majority of cases of diarrhoea were related to medications and enteral tube feeding. A small but significant number did develop bacterial infections. In contrast to some suggested guidelines, when investigating hospital acquired diarrhoea, it is considered worthwhile to perform microbiological stool examinations.

Adult↗
PubMed1997

A prospective randomized controlled trial of oral ciprofloxacin in acute ulcerative colitis.

OBJECTIVES: The aim of this prospective, randomized, controlled trial was to evaluate the role of ciprofloxacin as an adjunct to corticosteroids in acute ulcerative colitis. METHODS: Seventy consecutive patients with mild (n = 37) or moderately active (n = 33) ulcerative colitis were randomized to receive oral ciprofloxacin (250 mg b.i.d., n = 34) or placebo (n = 36) for 14 days. In addition, they were given oral prednisolone (initial dose 20 or 40 mg for mild and moderately active ulcerative colitis, respectively) and rectal betamethasone enemas (2 g at night) for 7-9 weeks. All patients were receiving olsalazine (0.5 g twice daily). At study entry, the groups were similar with respect to age, sex, extent, duration, and severity of disease, and previous treatments. Patients were assessed clinically, endoscopically, and histologically before, at the end of the trial (day 14), and on completion of steroid treatment, or at any time worsening of symptoms or a complication of ulcerative colitis occurred. RESULTS: At the end of the study, 24 patients (70.5%) in the ciprofloxacin group and 26 patients (72%) in the placebo group achieved remission (p > 0.1, Yates chi 2). Ten patients in each group necessitated higher doses of oral (n = 12) or intravenous (n = 8) steroids. Of the latter patients, two underwent emergency colectomy without perioperative deaths. Clostridium difficile toxin A was not detected in nonresponders to ciprofloxacin treatment. CONCLUSIONS: A short course of oral ciprofloxacin treatment does not seem to increase the proportion of patients with active ulcerative colitis going into remission.

Acute Disease↗
PubMed1996

[Antibiotic-induced diarrhea: recent findings about Clostridium difficile].

From the beginning of the antibiotherapy, diarrhea frequently occurred as a side effect of the treatment. The spectrum of diarrheal disease associated with antibiotic therapy ranges from antibiotic associated diarrhea and colitis, to the more severe pseudomembranous colitis, which is always associated with Clostridium difficile (CD). Because most of the antibiotics are not active against this sporulated Gram positive anaerobe. The pathogenic process occurs only by production of toxins. CD is now recognized as one of the most important hospital infections. Although therapy is available for the majority of patients with CD infection, pseudomembranous colitis is a serious disease which, if untreated, can lead to major complications.

Adult↗
PubMed2006

Prevalence of Clostridium difficile colonization at admission to rehabilitation.

OBJECTIVES: To assess the prevalence of intestinal colonization with Clostridium difficile (C. difficile) at admission to acute rehabilitation and to identify risk factors associated with colonization. DESIGN: Case-control study. PARTICIPANTS: Consecutive admissions to 2 rehabilitation units (spinal cord injury, brain injury and stroke). SETTING: Free-standing acute rehabilitation facility. INTERVENTIONS: Rectal swabs for culture for C. difficile were obtained at admission and cytotoxin assay performed on all culture positive specimens. Rates of colonization with cytotoxic C. difficile were calculated. Charts were reviewed for medical and demographic factors that may have predisposed patients to colonization, and for possible symptoms at the time of admission. MAIN OUTCOME MEASURES: Percentage of patients with culture and cytotoxin assay positive for C. difficile. Frequency of specific patient characteristics that could predispose to C. difficile colonization. RESULTS: Of admission stool samples, 16.4% tested positive for C. difficile; none of these patients had been identified as colonized before admission. No patients were discordant for C. difficile positivity on culture and presence of a toxigenic strain. No medical or demographic factors were associated with increased risk of colonization, including age (t(52)=-.748, P=.458, not significant [NS]), diarrhea within 24 hours of admission (chi(1)(2) test=.001, P=.973 [NS]), or use of oral or intravenous antibiotics at admission (chi(1)(2) test=.044, P=.834 [NS]). CONCLUSIONS: Patients admitted to acute rehabilitation may have an elevated rate of intestinal colonization with C. difficile without having clinical symptoms. No medical or demographic characteristics were found to be predictive of colonization, however, most of the patients admitted had more than 1 factor that may have increased their susceptibility to infection with this organism. Inadvertent transfer of this organism within the rehabilitation setting may occur because asymptomatic colonization is not recognized.

Adult↗