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PubMed1996

Clostridium difficile colitis associated with cisplatin-based chemotherapy in ovarian cancer patients.

The purpose of this study was to examine the incidence and cause of Clostridium difficile colitis occurring after cisplatin-based combination chemotherapy in ovarian cancer patients. Thirty-three patients with primary ovarian malignancy were treated with cisplatin-based combination chemotherapy ranging from 1 to 12 (mean 4.6) cycles. All patients who developed diarrhea after undergoing the cancer chemotherapy were examined to determine whether or not they were complicated by C difficile colitis. The diagnosis of C. difficile was confirmed by a stool-cytotoxin test and endoscopic examination. Severe C. difficile colitis occurred in 2 patients (6.1%) after receiving cisplatin-based combination chemotherapy for ovarian malignancies. Although both patients recovered from the colitis after the administration of vancomycin, the first case demonstrated a relapse of the colitis after receiving a subsequent course of the same chemotherapy with cisplatin. Both patients were then treated with a carboplatin alternative to cisplatin in the following courses, which resulted in neither a relapse of the colitis nor a recurrence of the malignancies up to this time. This report suggests the importance of searching for the presence of C. difficile and its toxin in patients with diarrhea after undergoing cancer chemotherapy since C. difficile may cause severe colitis. Based on our findings, it is thus concluded that cisplatin may cause C. difficile colitis.

Adult↗
PubMed1994

Intravenous teicoplanin does not prevent Clostridium difficile associated diarrhea.

A 59-year-old man with the diagnosis of endocarditis of the mitral valve due to Streptococcus mitis was treated with penicillin G, gentamicin, and later with clindamycin as inpatient for 3 weeks. Thereafter outpatient therapy with parenteral teicoplanin 3 x per week was initiated. After 17 days of teicoplanin treatment he developed severe diarrhea, and stool samples were positive for Clostridium difficile toxin. In addition to the ongoing parenteral therapy with teicoplanin, oral teicoplanin was administered. On the third day of this regimen the diarrhea and other disabling symptoms subsided, and test results for C. difficile toxin became negative. Oral teicoplanin was continued for 10 days and cleared C. difficile effectively after treatment as assessed by consecutive stool cultures (until 60 days thereafter). The parenteral administration of teicoplanin could not prevent the onset of C. difficile associated diarrhea in this patient, who previously had been treated with clindamycin. Thus, the administration of parenteral teicoplanin does not seem to be a treatment option for C. difficile associated diarrhea in patients in which oral therapy is not possible.

Clostridioides difficile↗
PubMed1992

Effect of yogurt on clindamycin-induced Clostridium difficile colitis in hamsters.

Yogurt exhibits in vitro bactericidal activity against a variety of pathogenic microorganisms, including Clostridium difficile. In the present studies, we tested whether yogurt ingestion could prevent or ameliorate antibiotic associated colitis in the clindamycin-treated hamster model. Male golden Syrian hamsters were given 5 mg/kg clindamycin subcutaneously 24 hr before and 6 hr following inoculation with 0.5 ml of less than 10, 10(3), 10(5), or 10(6) CFU/ml of C. difficile. Hamsters in the control group ingested chow and water ad libitum, whereas the experimental group ingested chow and a 1:1 (v/v) mixture of yogurt and water ad libitum, beginning 24 hr before the first injection of clindamycin and continuing throughout the course of the study. Animals were monitored for colonization with C. difficile, pathological evidence of colitis, and death. Mortality was 100% in yogurt-treated animals, and all animals showed histological changes of severe colitis. Fecal and intestinal segment cultures were positive for C. difficile in all animals. Thus, in the hamster model, we found no evidence to support the possible efficacy of yogurt in the prevention of C. difficile colitis.

Animals↗
PubMedDate not supplied

Detection of Clostridium difficile toxin by enzyme immunoassay, tissue culture test and culture.

Clostridium difficile toxin is frequently encountered in patients with antibiotic-associated diarrhea. A commercially available enzyme immunoassay (EIA) detecting toxins A and B was evaluated, screening 148 stool specimens specifically submitted for the detection of C. difficile. A sensitivity of 100% and a specificity of 97.5% were found compared to a tissue culture assay. The overall prevalence of C. difficile toxin was 22.1%. Cephalosporins had been administered significantly more often to toxin-positive patients. The EIA proved to be a suitable test for the detection of C. difficile toxin, revealing high prevalences in specifically submitted clinical specimens.

Bacterial Proteins↗
PubMed2006

Inhibition of Clostridium difficile growth and adhesion to enterocytes by Bifidobacterium supernatants.

The antimicrobial and anti-adhesive effects of extracellular factors from 27 strains of bifidobacteria isolated from healthy infants were tested against two reference strains of Clostridium difficile (ATCC 9689 and ATCC 43593). All bifidobacterial supernatants at pHs between 5.0 and 4.1 were able to produce strain-dependent growth inhibition of clostridia in the agar-diffusion assay. Six strains of Bifidobacterium produced during growth extracellular factors able to antagonize the adhesion of C. difficile ATCC 9689 and ATCC 43593 to cultured human enterocytes (Caco-2/TC7). Factors responsible for the anti-adhesive effect were thermolabile, active at neutral pH and unaffected by proteolytic cleavage (proteinase K and chymotrypsin). Results of the present paper show the potential of selected bifidobacteria to antagonize key mechanisms involved in the virulence of C. difficile.

Antibiosis↗
PubMed2006

Toxin A-negative, toxin B-positive Clostridium difficile.

Clostridium difficile is a major cause of infectious diarrhea in hospitalized patients. Many pathogenic strains of Clostridium difficile produce two toxins TcdA and TcdB, both of which are pro-inflammatory and enterotoxic in human intestine. Clinically relevant toxin A-negative, toxin B-positive (A(-)B(+)) strains of Clostridium difficile that cause diarrhea and colitis in humans have been isolated with increasing frequency worldwide. This perspective describes these important toxin variant strains and highlights the need to use Clostridium difficile diagnostic methods that can detect both TcdA and TcdB.

Bacterial Proteins↗
PubMed1998

Incidence and impact of Clostridium difficile infection in the UK, 1993-1996.

Questionnaires were sent to 360 UK medical microbiologists to determine the incidence of Clostridium difficile infection in the UK between 1993-1996, and to establish the current laboratory testing protocols. Replies were received from 104 laboratories (29% response rate), 86, 7, 4 and 3% of which are in England, Scotland, Wales and Northern Ireland, respectively. The laboratories serve a total of approximately 90,000 hospital beds (median 750). C. difficile testing was performed by 83% of the laboratories, and 52, 45 and 31% used toxin A +/- B kits, cell cytotoxicity, and culture +/- isolate toxigenicity testing methods, respectively. Forty-seven percent of laboratories only performed testing when specifically requested, 19% if antibiotic use was stated, 15% tested all diarrhoeal specimens, and 14% examined all specimens except those from infants and community patients. The annual totals of positive C. difficile reports and cases increased from 3132 to 12,775, and from 1576 to 8211, respectively, between 1993-1996. In 1993 C. difficile infection caused ward closures in 5% of hospitals but 16% in 1996. Antibiotic policy changes, due to C. difficile infection, occurred in 21% of hospitals in 1996 compared with only 4% in 1993. C. difficile infection appears to be increasing markedly in the UK with major implications on hospital inpatient activity. Wide variations in laboratory selection and testing methods are likely to be masking the true epidemiology of C. difficile infection, and consensus is required on optimal protocols.

Aged↗
PubMed1991

Gastrointestinal carriage of Clostridium difficile in cats and dogs attending veterinary clinics.

Cats and dogs being treated at two veterinary clinics were investigated for gastrointestinal carriage of Clostridium difficile using selective solid and enrichment media. Thirty-two (39.5%) of 81 stool samples yielded C. difficile. There were significant differences in isolation rates between clinics, 61.0% of animals being positive at one clinic compared to 17.5% at the other (Chi-square, P less than 0.005). Of 29 animals receiving antibiotics, 15 (52.0%) harboured C. difficile while 11 (23.9%) of 46 animals not receiving antibiotics were positive (Chi-square, P less than 0.01). There was no difference in carriage rate between cats (38.1%) and dogs (40.0%). The environment at both veterinary clinics was surveyed for the presence of C. difficile. Fifteen of 20 sites at one clinic were positive compared to 6 of 14 sites at the other clinic. Both cytotoxigenic and noncytotoxigenic isolates of C. difficile were recovered from animals and environmental sites. These findings suggest that household pets may be a potentially significant reservoir of infection with C. difficile.

Animals↗
PubMed2002

Underlying disease severity as a major risk factor for nosocomial Clostridium difficile diarrhea.

OBJECTIVE: To determine the diagnostic accuracy of an index of underlying disease severity (Horn's index) in identifying patients with a high probability of having nosocomial Clostridium difficile diarrhea as a complication of antimicrobial therapy. DESIGN: A prospective cohort study of 252 adult patients admitted to the hospital and receiving antibiotics. Risk facctors for C. difficile diarrhea were first determined retrospectively in a different cohort of 300 hospitalized patients (primary cohort) and then prospectively in this cohort of 252 hospitalized patients receiving antibiotics (secondary cohort). At the time of hospital admission, disease was rated by clinicians as mild (1), moderate (2), severe (3), or extremely severe (4) using a modified Horn's index. Multivariable logistic regression analysis was used to determine the odds ratio (OR) for C. difficile diarrhea associated with increasing levels of disease severity. SETTING: An urban teaching hospital affiliated with a medical school in Boston, Massachusetts. RESULTS: The incidence of nosocomial C. difficile diarrhea was 8.7% in the primary cohort and 11% in the secondary cohort In the prospective cohort study (secondary cohort), the OR for C. difficile diarrhea associated with extremely severe disease was 17.6 (95% confidence interval, 5.8 to 53.5). The sensitivity, specificity, and positive and negative predictive values of a Horn's index score of 3 or more (severe to extremely severe disease) as a predictor of nosocomial C. difficile diarrhea were 79%, 73%, 27%, and 96%, respectively. CONCLUSIONS: These findings provide a means of early stratification of hospitalized patients receiving antibiotics according to their risk for nosocomial C. difficile diarrhea. Patients with severe to extremely severe disease at the time of admission may benefit from careful monitoring of antibiotic prescribing and early attention to infection control issues. In the future, these "high-risk" patients may benefit from prophylaxis studies of novel agents being developed to prevent C. difficile diarrhea.

Adolescent↗
PubMed2003

Favorable impact of a multidisciplinary antibiotic management program conducted during 7 years.

OBJECTIVE: To evaluate the impact of an interventional multidisciplinary antibiotic management program on expenditures for antibiotics and on the incidence of nosocomial infections caused by Clostridium difficile and antibiotic-resistant pathogens during 7 years. DESIGN: Prospective study with comparison with preintervention trends. SETTING: University-affiliated teaching hospital. PATIENTS: All adult inpatients. INTERVENTION: A multidisciplinary antibiotic management program to minimize the inappropriate use of third-generation cephalosporins was implemented in 1991. Its impact was evaluated prospectively. The incidence of nosocomial C. difficile and resistant Enterobacteriaceae infections as well as the rate of vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) were compared with those of National Nosocomial Infections Surveillance System hospitals of similar size. RESULTS: Following implementation of the program, there was a 22% decrease in the use of parenteral broad-spectrum antibiotics (P < .0001) despite a 15% increase in acuity of patient care during the following 7 years. Concomitantly, there was a significant (P = .002) decrease in nosocomial infections caused by C. difficile and a significant (P = .02) decrease in nosocomial infections caused by resistant Enterobacteriaceae. The program also appeared to have a favorable impact on VRE rates without a sustained impact on MRSA rates. CONCLUSION: These results suggest that an ongoing multidisciplinary antibiotic management program may have a sustained beneficial impact on both expenditures for antibiotics and the incidence of nosocomial infection by C. difficile and resistant bacterial pathogens.

Anti-Bacterial Agents↗
PubMed2004

CdeA of Clostridium difficile, a new multidrug efflux transporter of the MATE family.

The cdeA gene, cloned from Clostridium difficile clinical strain 714 under the control of its natural promoter made Escherichia coli and Clostridium perfringens resistant to ethidium bromide and acriflavin but had no effect on the susceptibility of the hosts to the following antibiotics: norfloxacin, ciprofloxacin, gentamicin, erythromycin, tetracyclin, and chloramphenicol. However, it was responsible for fluoroquinolone resistance in E. coli when it was cloned under the control of the Plac promoter. Quantitative reverse transcriptase (RT)-PCR showed that growth of C. difficile clinical strain 253 in the presence of subinhibitory concentrations of ethidium bromide significantly increased the transcription of cdeA, but this was not observed with ciprofloxacin. The deduced protein was homologous to the protein sequences of known efflux pumps from the third cluster (the so-called DinF branch) of the multidrug and toxic compound extrusion (MATE) family. CdeA caused ethidium bromide energy-dependent efflux in whole cells of E. coli. Efflux activity was stimulated by addition of Na+ ions, suggesting that CdeA, like other pumps of the MATE family, is a Na+-coupled efflux pump. CdeA is the first multidrug efflux transporter identified in C. difficile.

Amino Acid Sequence↗