Pseudomembranous colitis: causes and cures.
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Clostridium difficile is the most common nosocomial pathogen of the gastrointestinal tract and has increased in frequency over time. Typical symptoms of C. difficile infection include diarrhea, which is usually nonbloody, or colitis associated with severe abdominal pain, fever and/or gross or occult blood in the stools. Pseudomembranous colitis (PMC), the severest form of this disease, occurs as a result of a severe inflammatory response to the C. difficile toxins. This review focuses on PMC, as this severe form is associated with the greatest medical concern. Diagnosis rests on detection of C. difficile in the stool, either by culture, tissue culture assay for cytotoxin B or detection of antigens in the stool by rapid enzyme immunoassays. Oral therapy with metronidazole 250 mg 4 times a day for 10 days is the recommended first-line therapy. Vancomycin is also effective, but its use must be limited to decrease the development of vancomycin-resistant organisms such as enterococci. Vancomycin (125-500 mg 4 times a day for 10 days) should be limited to those who cannot tolerate or have not responded to metronidazole, or when metronidazole use is contraindicated, as in the first trimester of pregnancy. A therapeutic response within a few days is usual. Recurrence of symptoms after antibiotics occurs in 20% of cases and is associated with persistence of C. difficile in the stools. Further recurrences then become more likely. Therapy with antibiotics in a pulsed or tapered regimen is often effective as are efforts to normalize the fecal flora. The yeast Saccharomyces boulardii has been proven in controlled trials to reduce recurrences when given as an adjunct to antibiotic therapy. Careful hand washing and environmental decontamination are necessary to prevent epidemics. (+info)
At our hospital, the number of cases of Clostridium difficile-associated diarrhoea increased from 29 in 1993 to 210 in 1995. The case notes of 110 patients with C difficile-associated diarrhoea during the first 6 months of 1995 were analysed retrospectively. The majority of the patients (106) had received antibiotics before the onset of diarrhoea; 46 had received three or more different antibiotics and 28 had received metronidazole. In 19 patients, the first stool sample after the onset of diarrhoea was negative for C difficile cytotoxin, with a mean delay of 8.2 days before a positive stool sample. We conclude that C difficile-associated diarrhoea was associated with the usage of multiple antibiotics, and that metronidazole did not protect against colonisation by C difficile. We also recommend that more than one stool sample should be tested for the C difficile cytotoxin. (+info)
Immunogenicity of a Salmonella typhimurium aroA aroD vaccine expressing a nontoxic domain of Clostridium difficile toxin A.
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The C-terminal repeat domain of Clostridium difficile toxin A harbors toxin-neutralizing epitopes and is considered to be a candidate component of a vaccine against C. difficile-associated disease (CDAD). Fourteen of the 38 C-terminal toxin A repeats (14CDTA) were cloned into pTECH-1 in frame with the immunogenic fragment C of tetanus toxin (TETC) to generate plasmid p56TETC. Expression of the TETC-14CDTA fusion protein was driven from the anaerobically inducible nirB promoter within attenuated Salmonella typhimurium BRD509 (aroA aroD). The TETC-14CDTA fusion protein was purified and shown to bind to known toxin A receptors found on the surface of rabbit erythrocytes. Intranasal (i.n.) and intragastric (i.g.) immunization with 10(7) and 10(10) CFU, respectively, of BRD509(p56TETC) generated significant (P < 0.05) anti-toxin A serum responses after a single dose. Antibody titers were elevated following a boosting dose with either live vaccine or a subcutaneous injection of 0.5 microgram of purified 14CDTA protein. Importantly, serum from mice immunized with BRD509(p56TETC) neutralized toxin A cytotoxicity. Both i.n. and i.g. immunizations also generated toxin A-specific immunoglobulin A on the pulmonary and intestinal mucosa, respectively. Intranasal vaccination induced consistently higher serum and mucosal anti-toxin A antibody responses. Significant anti-tetanus toxoid serum and mucosal antibodies were also generated by both immunization routes. The availability of live attenuated Salmonella typhi for human use may allow the development of a multivalent mucosal vaccine against CDAD, tetanus, and typhoid. (+info)
Incidence and outcome of Clostridium difficile infection following autologous peripheral blood stem cell transplantation.
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A retrospective evaluation of 200 consecutive recipients of autologous peripheral blood stem cell transplantation (PBSCT) was conducted to ascertain the incidence and outcome of infection with Clostridium difficile. The diagnosis was confirmed in 14 patients with diarrhea (15 episodes) at a median of 33 days after stem cell infusion. Five patients were neutropenic at the time of diagnosis. Every individual had adverse known risk factors such as recent or current use of antibiotic, corticosteroid and antiviral therapy, recent administration of myeloablative chemotherapy and numerous, prolonged periods of hospitalization. Diarrhea, frequently hemorrhagic, was the most common presenting feature along with fever, abdominal cramps and abdominal distention. Diagnosis was established by the stool-cytotoxin test. Response to standard treatment with oral vancomycin or metronidazole was prompt despite the presence of several adverse prognostic features in these patients. There was only one instance of relapse which was also treated successfully. Several transplant-related variables such as age, sex, underlying malignancy, myelo-ablative regimen, duration of neutropenia, and prophylactic use of oral ampicillin underwent statistical analysis but failed to be predictive of C. difficile infection in such a setting. Finally, C. difficile is not uncommon after autologous PBSCT and must be included in the differential diagnosis in any such patient with diarrhea. (+info)
Clostridium difficile cell attachment is modified by environmental factors.
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Adherence of Clostridium difficile to Vero cells under anaerobic conditions was increased by a high sodium concentration, calcium-rich medium, an acidic pH, and iron starvation. The level of adhesion of nontoxigenic strains was comparable to that of toxigenic strains. Depending on the bacterial culture conditions, Vero cells could bind to one, two, or three bacterial surface proteins with molecular masses of 70, 50, and 40 kDa. (+info)
Clostridium difficile colitis associated with infant botulism: near-fatal case analogous to Hirschsprung's enterocolitis.
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We present the first five reported cases of Clostridium difficile-associated diarrhea (CDAD) in children with infant botulism caused by Clostridium botulinum. We compare two fulminant cases of colitis in children with colonic stasis, the first caused by infant botulism and the second caused by Hirschsprung's disease. In both children, colitis was accompanied by hypovolemia, hypotension, profuse ascites, pulmonary effusion, restrictive pulmonary disease, and femoral-caval thrombosis. Laboratory findings included pronounced leukocytosis, hypoalbuminemia, hyponatremia, coagulopathy, and, when examined in the child with infant botulism, detection of C. difficile toxin in ascites. CDAD recurred in both children, even though difficile cytotoxin was undetectable in stool after prolonged initial therapy. Four children who had both infant botulism and milder CDAD also are described. Colonic stasis, whether acquired, as in infant botulism, or congenital, as in Hirschsprung's disease, may contribute to the susceptibility to and the severity of CDAD. (+info)
Antimicrobial susceptibilities and serogroups of clinical strains of Clostridium difficile isolated in France in 1991 and 1997.
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Glycopeptides (vancomycin and teicoplanin) and metronidazole are the drugs of choice for the treatment of Clostridium difficile infections, but trends in susceptibility patterns have not been assessed in the past few years. The objective was to study the MICs of glycopeptides and metronidazole for unrelated C. difficile strains isolated in 1991 (n = 100) and in 1997 (n = 98) by the agar macrodilution, the E-test, and the disk diffusion methods. Strain susceptibilities to erythromycin, clindamycin, tetracycline, rifampin, and chloramphenicol were also determined by the ATB ANA gallery (bioMerieux, La Balme-les-Grottes, France). The MICs at which 50% of isolates are inhibited (MIC(50)s) and MIC(90)s of glycopeptides and metronidazole remained stable between 1991 and 1997. All the strains were inhibited by concentrations that did not exceed 2 microgram/ml for vancomycin and 1 microg/ml for teicoplanin. Comparison of MICs determined by the agar dilution method recommended by the National Committee for Clinical Laboratory Standards and the E test showed correlations (+/-2 dilutions) of 86. 6, 95.9, and 99% for metronidazole, vancomycin, and teicoplanin, respectively. The E test always underestimated the MICs. Strains with decreased susceptibility to metronidazole (MICs, >/=8 microgram/ml) were isolated from six patients (n = 4 in 1991 and n = 2 in 1997). These strains were also detected by the disk diffusion method (zone inhibition diameter, /=1 microgram/ml), clindamycin (MICs, >/=2 microgram/ml), tetracycline (MICs, >/=8 microgram/ml), rifampin (MICs, >/=4 microgram/ml), and chloramphenicol (MICs, >/=16 microgram/ml) was observed in 64.2, 80.3, 23.7, 22.7, and 14.6% of strains, respectively. Strains isolated in 1997 were more susceptible than those isolated in 1991, and this trend was correlated to a major change in serogroup distribution. Periodic studies are needed in order to detect changes in serogroups and the emergence of strains with decreased susceptibility to therapeutic drugs. (+info)
Predominant Staphylococcus aureus isolated from antibiotic-associated diarrhea is clinically relevant and produces enterotoxin A and the bicomponent toxin LukE-lukD.
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Staphylococcus aureus was isolated as the predominant or only isolate from cultures of stools of 60 patients over 2 years in a university hospital, leading to the collection of 114 isolates. Diarrhea was observed in 90% of the patients. Ninety-eight percent of the patients had received antibiotics in the month before the diarrhea. Ninety-two percent of the S. aureus isolates were methicillin resistant. S. aureus was encountered with antibiotic-associated diarrhea among 47 quite elderly patients affected or not affected by a gastrointestinal disease. Among the antimicrobial treatments, cessation of the previous therapy when possible or rapid application of oral vancomycin therapy was the most appropriate. Analysis of total DNA by pulsed-field gel electrophoresis revealed 27 different SmaI pulsotypes distributed in 15 clusters. The pulsotypes never differed for related isolates from a single patient, even if they originated from patients with bacteremia. S. aureus was not isolated as the predominant isolate in cultures of stools of 57 patients who received an antimicrobial treatment for more than 5 days without diarrhea. Occurence of production of both enterotoxin A and the bicomponent leucotoxin LukE-LukD by the S. aureus isolates was significantly different from that by random isolates. The results strongly suggest that when predominant in stool samples, S. aureus should be considered a possible etiologic agent for some cases of antibiotic-associated diarrhea. (+info)