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PubMed1991

Antibiotic resistance of Clostridium difficile isolates.

The activity of metronidazole, vancomycin, clindamycin and teicoplanin against Clostridium difficile strains isolated from various origins in Poland was investigated. MIC was determined for metronidazole, clindamycin and teicoplanin. The disc-diffusion method was used for the vancomycin susceptibility test. Three out of thirty-eight strains were resistant to vancomycin and twenty-eight were susceptible to teicoplanin. A widespread MIC was observed for clindamycin and metronidazole. No correlation between the origin of the strain, toxigenicity and susceptibility to teicoplanin, clindamycin, vancomycin and metronidazole was evident.

Adolescent↗
PubMed2005

Antibiotic treatment for Clostridium difficile-associated diarrhea in adults.

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

Adult↗
PubMedDate not supplied

Medical technologists using molecular epidemiology as part of the infection control team.

Two medical technologists were appointed as permanent members of a new epidemiology section in the diagnostic microbiology laboratory of a large Veterans Administration Medical Center in the fall of 1989. These positions accounted for 9% of the total microbiology staff and were created on a temporary basis 2 years earlier from a need to have dedicated technical expertise for use in the culture, isolation, and typing of nosocomial organisms. The technologists have evaluated outbreaks due to Clostridium difficile, methicillin-susceptible Staphylococcus aureus, and Serratia marcescens, and have begun work on a methicillin-resistant Staphylococcus aureus (MRSA)-typing scheme. Their major responsibility has been the development and application of molecular biology techniques for the typing of nosocomial isolates, including restriction enzyme analysis of genomic DNA, plasmid profiling with and without restriction enzyme analysis, ribosomal RNA probing of restricted genomic DNA, and selected DNA sequencing of target organisms. Medical supervision rests jointly between the directors of the infection control program and the microbiology laboratory. During their tenure, infections due to C. difficile have dropped from 95 cases per year to 57 cases annually, treatment of MRSA colonization with systemic agents has been curtailed, and a case control investigation involving S. marcescens was avoided. The inclusion of medical technologists in the infection control practice of large medical care facilities, particularly with the availability of molecular epidemiologic techniques and the emergence of increasing numbers of multiply-drug-resistant pathogens, will become an essential component of these programs.

Bacterial Infections↗
PubMed1998

The complete DNA sequence and analysis of the large virulence plasmid of Escherichia coli O157:H7.

The complete DNA sequence of pO157, the large virulence plasmid of EHEC strain O157:H7 EDL 933, is presented. The 92 kb F-like plasmid is composed of segments of putative virulence genes in a framework of replication and maintenance regions, with seven insertion sequence elements, located mostly at the boundaries of the virulence segments. One hundred open reading frames (ORFs) were identified, of which 19 were previously sequenced potential virulence genes. Forty-two ORFs were sufficiently similar to known proteins for suggested functions to be assigned, and 22 had no convincing similarity with any known proteins. Of the newly identified genes, an unusually large ORF of 3169 amino acids has a putative cytotoxin active site shared with the large clostridial toxin (LCT) family and proteins such as ToxA and B of Clostridium difficile . A conserved motif was detected that links the large ORF and the LCT proteins with the OCH1 family of glycosyltransferases. In the complete sequence, the mosaic form can be observed at the levels of base composition, codon usage and gene organization. Insights were obtained from patterns of DNA composition as well as the pathogenic and 'housekeeping' gene segments. Evolutionary trees built from shared plasmid maintenance genes show that even these genes have heterogeneous origins.

Amino Acid Sequence↗
PubMed1992

Correlation between cytotoxin production and sporulation in Clostridium difficile.

Correlation between cytotoxin production and sporulation was demonstrated when a Clostridium difficile culture was inoculated into fresh broth to give an initial count of less than 10 vegetative cells/ml with no spores. Under these conditions, cytotoxin was produced and released during sporulation. Addition of a sporulation inhibitor (acridine orange, 30 mg/L), resulted in a marked decrease in both sporulation and cytotoxin production, despite there being no change in the number of vegetative cells in the culture. These results indicate that sporulation might be closely related to cytotoxin production.

Acridine Orange↗
PubMed2006

Past, present, and future therapies for Clostridium difficile-associated disease.

OBJECTIVE: To describe and examine the past, present, and potential future treatment options for Clostridium difficile-associated disease (CDAD). DATA SOURCES: A PubMed search, restricted to English-language articles concerning CDAD, was conducted (1965-October 2006) using the key words Clostridium difficile, diarrhea, vancomycin, metronidazole, immunoglobulin, and recurrence. Additional references were located through review of the bibliographies of cited articles and by visiting www.clinicaltrials.gov. STUDY SELECTION AND DATA EXTRACTION: Articles related to the clinical manifestations, diagnosis, and treatment of CDAD, as well as articles addressing current issues related to CDAD, were included. DATA SYNTHESIS: There have been many investigations into CDAD because of the recent increased incidence and morbidity and mortality of the disease. Various studies examining the changing epidemiology and pathogenicity of C. difficile, as well as new therapies for CDAD with agents such as tolevamer and nitazoxanide, are ongoing. In addition, researchers are investigating probiotics and vaccines to evaluate their effectiveness in preventing CDAD and/or preventing recurrences of CDAD. Studies assessing therapies for refractory CDAD are lacking, although case reports have been published citing treatment strategies using vancomycin enemas, intravenous metronidazole, colestipol and cholestyramine, fecal enemas, bowel irrigation, and immunoglobulin. Furthermore, judicious use of antimicrobials, contact precautions, and adequate environmental cleaning are being evaluated in healthcare institutions as methods for controlling and preventing the spread of C. difficile. CONCLUSIONS: Oral metronidazole is the drug of choice for an initial CDAD episode. Oral vancomycin is an option for patients who cannot take or fail treatment with oral metronidazole. Clinical trials are necessary to define the therapy for initial CDAD that is most appropriate and produces lower recurrence rates compared with oral metronidazole or vancomycin treatment. Moreover, appropriate treatment for patients with multiple recurrences of or refractory CDAD needs to be determined. More studies are also needed assessing prevention of recurrences of CDAD.

Clostridioides difficile↗
PubMed2006

Narrative review: the new epidemic of Clostridium difficile-associated enteric disease.

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

Clostridioides difficile↗
PubMed2004

Severe ciprofloxacin-associated pseudomembranous colitis in an eight-year-old child.

Clostridium difficile is the principal cause of antibiotic-associated diarrhea and pseudomembranous enterocolitis in children. A case of severe pseudomembranous colitis developing in an 8-year-old child who had received oral ciprofloxacin therapy as part of an investigational protocol is presented. The safety and efficacy of fluoroquinolones in children has not yet been established. Use of these antibiotics in children outside investigational protocols ("off-label" use) as oral antipseudomonas agents is discouraged.

Anti-Infective Agents↗
PubMed1993

Reactive arthritis associated with Clostridium difficile pseudomembranous colitis.

Reactive arthritis is associated with several gastrointestinal pathogens, particularly Shigella, Salmonella, Campylobacter, and Yersinia. Another, less well recognized bowel infection leading to reactive arthritis is pseudomembranous colitis, caused by Clostridium difficile. An illustrative case is presented, and the clinical features and characteristics of all reported patients with this association are reviewed. The pathogenesis of the reactive arthritis seems to be related to an immunological response in joints and other tissues against bacterial antigens, which gain access to the systemic circulation through increased intestinal permeability. Therapy with nonspecific antiinflammatory drugs, anticlostridial agents, or a combination of the above is effective. Despite the possibility of persistent articular involvement after gastrointestinal symptoms have subsided, the long-term prognosis seems to be excellent.

Arthritis, Reactive↗
PubMed1990

Virulence of ten serogroups of Clostridium difficile in hamsters.

A slide agglutination technique identifying 10 serogroups of Clostridium difficile (A,B,C,D,F,G,H,I,K and X) has been described previously. In this study, we have used the hamster to compare the ability of the 10 serogroup reference strains to colonise and produce disease. Groups of four hamsters were each given a single intraperitoneal injection of either clindamycin or cefoxitin, and an oral challenge dose of C. difficile. The time taken to establish faecal colonisation and the length of survival after colonisation were monitored. All hamsters treated with cefoxitin became colonised by day 3 and those challenged with the cytotoxigenic strains of serogroups A,C,H and K developed colitis and died. Among those challenged with the non-toxigenic strains of groups B,D,I and X and the toxigenic strains of groups F and G, faecal colonisation was established without signs of disease. This demonstrates that there are differences in virulence even among toxigenic strains of C. difficile. The same phenomenon was observed after treatment with clindamycin but the pattern of colonisation was quite different with some strains. In the hamsters challenged with toxigenic strains of groups C and K and non-toxigenic strains of groups D and I, which are highly resistant to clindamycin, the response was the same as with cefoxitin. The results were different with strains which were susceptible to clindamycin. Some animals became colonised much later than those treated with cefoxitin but the mortality was similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

Demonstration that the group II intron from the Clostridial Conjugative transposon Tn5397 undergoes splicing In vivo.

Previous work has identified the conjugative transposon Tn5397 from Clostridium difficile. This element was shown to contain a group II intron. Tn5397 can be conjugatively transferred from C. difficile to Bacillus subtilis. In this work we show that the intron is spliced in both these hosts and that nonspliced RNA is also present. We constructed a mutation in the open reading frame within the intron, and this prevented splicing but did not prevent the formation of the circular form of the conjugative transposon (the likely transposition intermediate) or decrease the frequency of intergeneric transfer of Tn5397. Therefore, the intron is spliced, but splicing is not required for conjugation of Tn5397.

Bacillus subtilis↗
PubMed2003

Antimicrobial susceptibilities of canine Clostridium difficile and Clostridium perfringens isolates to commonly utilized antimicrobial drugs.

Clostridium difficile and Clostridium perfringens are anaerobic, Gram-positive bacilli that are common causes of enteritis and enterotoxemias in both domestic animals and humans. Both organisms have been associated with acute and chronic large and small bowel diarrhea, and acute hemorrhagic diarrheal syndrome in the dog. The objective of this study was to determine the in vitro antimicrobial susceptibilities of canine C. difficile and C. perfringens isolates in an effort to optimize antimicrobial therapy for dogs with clostridial-associated diarrhea. The minimum inhibitory concentrations (MIC) of antibiotics recommended for treating C. difficile (metronidazole, vancomycin) and C. perfringens-associated diarrhea in the dog (ampicillin, erythromycin, metronidazole, tetracycline, tylosin) were determined for 70 canine fecal C. difficile isolates and 131 C. perfringens isolates. All C. difficile isolates tested had an MIC of or=256 microg/ml for both erythromycin and tylosin. A third C. perfringens isolate had an MIC of 32 microg/ml for metronidazole. Based on the results of this study, ampicillin, erythromycin, metronidazole, and tylosin appear to be effective antibiotics for the treatment of C. perfringens-associated diarrhea, although resistant strains do exist. However, because there is limited information regarding breakpoints for veterinary anaerobes, and because intestinal concentrations are not known, in vitro results should be interpreted with caution.

Ampicillin↗
PubMed2002

Clindamycin resistant strains of Clostridium difficile isolated from cases of C. difficile associated diarrhea (CDAD) in a hospital in Sweden.

Fifty three strains of C. difficile recovered from the stools of 13 patients with clinical C. difficile associated diarrhea (CDAD) were analyzed for the presence of the ermB gene, for toxigenicity and fingerprinting profile by PCR based assays. Forty five percent of the isolates were resistant to clindamycin and positive for the ermB gene. All clindamycin resistant isolates were ermB positive and belonged to the same fingerprinting group, suggesting clonal spread. These preliminary results suggest that clindamycin resistant isolates may be common etiologic agents of CDAD in Sweden.

Adult↗
PubMed1999

Fusidic acid in other infections.

Fusidic acid, both systemic and topical, has been used for a wide variety of less common infections. Efficacy for oral fusidic acid has been demonstrated in the treatment of Clostridium difficile colitis and in staphylococcal infections in patients with cystic fibrosis. Topical fusidic acid gel is also effective in bacterial conjunctivitis and other minor external eye infections, and may be effective in reducing bacterial flora in the conjunctival sac prior to eye surgery. Studies suggest a potential role for fusidic acid in neurosurgical prophylaxis, as adjunctive therapy in bacterial endophthalmitis and Legionella pneumonia, and in leprosy. Topical fusidic acid has no effect in the treatment of chlamydial conjunctivitis or the prevention of staphylococcal infections in patients on continuous ambulatory peritoneal dialysis.

Anti-Bacterial Agents↗
PubMed1998

Pseudomembraneous clostridium after autologous bone marrow transplantation.

Clostridium difficile (C. difficile) pseudomembraneous colitis was diagnosed in a 13-year-old boy with Hodgkin's disease 3 months after autologous bone marrow transplantation. Hematopoiesis was fully reconstituted at the time. C. difficile infection occurred after gall bladder empyema had been treated conservatively with i.v. antibiotics and prophylactic 4-week administration of oral amoxicillin. C. difficile colitis was diagnosed early and intensive supportive therapy combined with administration of i.v. and subsequently oral vancomycin therapy failed. It is a phenomenon rarely seen and successful eradication of the clostridium infection was only achieved by a combination of higher dose vancomycin with metronidazole. During the post-colitis recovery the patient experienced a relapse of Hodgkin's disease and died following further surgical intervention 137 days post-transplantation.

Adolescent↗
PubMed1993

Clostridium difficile: clinical disease and diagnosis.

Clostridium difficile is an opportunistic pathogen that causes a spectrum of disease ranging from antibiotic-associated diarrhea to pseudomembranous colitis. Although the disease was first described in 1893, the etiologic agent was not isolated and identified until 1978. Since clinical and pathological features of C. difficile-associated disease are not easily distinguished from those of other gastrointestinal diseases, including ulcerative colitis, chronic inflammatory bowel disease, and Crohn's disease, diagnostic methods have relied on either isolation and identification of the microorganism or direct detection of bacterial antigens or toxins in stool specimens. The current review focuses on the sensitivity, specificity, and practical use of several diagnostic tests, including methods for culture of the etiologic agent, cellular cytotoxicity assays, latex agglutination tests, enzyme immunoassay systems, counterimmunoelectrophoresis, fluorescent-antibody assays, and polymerase chain reactions.

Animals↗
PubMed2005

[Impact of a non-compulsory antibiotic control program (PACTA): cost reductions and decreases in some nosocomial infections].

BACKGROUND: Antibiotics account for 30% of hospital pharmacy expenses. More than 50% of the prescriptions are considered inappropriate; hence, programs devoted to optimizing the prescription of antibiotics should be developed. We present the results of a non-compulsory program for the assessment and control of antibiotic treatment in the University Hospital 12 de Octubre in Madrid. METHODS: The program was applied in the hospitalization units of six medical and surgical departments. Treatments in all patients were checked daily and recommendations were made in writing, according to previously established criteria. The program was used for 12 months and the results were compared with those of the previous 12 months. RESULTS: 1,280 treatments were reviewed and 524 recommendations were made (80% of them were accepted). There was a 13.82% reduction in the number of defined daily doses of antibiotics/100 inpatient-days. Antibiotic expenditure decreased by 65,352 euros (5,446 euros/month), implying a reduction of 1.21 euros/hospitalization-bed/day. There were no statistically significant differences in length of hospital stay or mortality between the two periods. A reduction in the incidence of Clostridium difficile diarrhea (p < 0.0001) and Candida spp. isolations (p < 0.05) was observed. CONCLUSIONS: Following application of a non-compulsory control program, antibiotic prescription improved and expenditure decreased, with no change in length of hospital stay or mortality. There was a reduction in the incidence of some nosocomial infections. Acceptation of the program by the physicians of the departments implicated was favorable.

Anti-Bacterial Agents↗
PubMed1996

Incidence of diarrhea with antibiotics and the increase of clostridia in rabbits.

Rabbits were treated with a single intravenous injection of various antibiotics. More than 40 per cent of the animals showed diarrhea after being treated with sulbactam/cefoperazone, cefmetazole, clindamycin, piperacillin or aspoxicillin. Clostridium difficile was isolated from sulbactam/cefoperazone-treated diarrheic rabbits, with their cecal contents showing positive reaction in a latex agglutination test for C. difficile enterotoxin. However, 27 cefmetazole-induced diarrheic cases were not associated with C. difficile. Other enteropathogenic bacteria, such as Campylobacter spp., Bacillus cereus, enteropathogenic Escherichia coli, coagulase positive Staphylococcus aureus, Salmonella spp., Vibrio spp., Clostridium perfringens and Clostridium spiroforme, were not isolated from either of diarrheic rabbit. However, the counts of clostridia remarkably increased in the intestine of cefmetazole-associated diarrheic rabbits. This was ascribed to the overgrowth of Clostridium innocuum and Clostridium sporogenes. There were no remarkable differences in changes in other bacterial population between diarrheic and non-diarrheic rabbits.

Animals↗