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Adjunctive intracolonic vancomycin for severe Clostridium difficile colitis: case series and review of the literature.

Successful treatment of severe Clostridium difficile colitis has been reported with the use of adjunctive intracolonic vancomycin (ICV) therapy. We report a descriptive case series and review the literature on patients with C. difficile colitis who received adjunctive ICV therapy. Nine patients received antibiotics within 6 weeks prior to presentation. Complete resolution of the clinical presentation occurred in 8 patients (88.9%), and eradication of C. difficile cytotoxin production was documented in 3 (75%) of 4 patients who were tested after the completion of adjunctive ICV therapy. One patient (11.1%) died as a result of progressive multisystem organ failure. In the 6 weeks after the completion of treatment for C. difficile colitis, no patient had recurrent disease, required surgical intervention, or experienced complications from adjunctive ICV therapy. In this case series, administration of adjunctive ICV therapy appeared to be a safe, practical, and effective adjunctive therapy for severe C. difficile colitis.

Adult↗

Reduction in the incidence of Clostridium difficile-associated diarrhea in an acute care hospital and a skilled nursing facility following replacement of electronic thermometers with single-use disposables.

OBJECTIVE: To determine if the spread of Clostridium difficile-associated diarrhea is related to the use of electronic thermometers in an acute hospital and a chronic healthcare facility. DESIGN: After finding that a significant percentage (20.8%) of electronic rectal thermometer handles were contaminated with C difficile, all electronic thermometers were replaced with disposables. A before/after trial was conducted to determine if the change to disposable thermometers would reduce the incidence of C difficile-associated diarrhea. SETTING: The study took place in a 343-bed acute hospital and a 538-bed skilled nursing facility. PATIENTS: All patients who underwent routine microbiological evaluation for nosocomially acquired diarrhea over a 1-year period were included in the study. Nosocomial diarrhea was defined as 3 or more loose stools per day for 2 consecutive days and/or abdominal findings such as pain, distension, and ileus occurring 3 or more days after admission. RESULTS: During the 6-month postintervention period, the incidence of C difficile-associated diarrhea was reduced from 2.71/1,000 patient days to 1.76/1,000 patient days in the acute hospital and from 0.41/1,000 patient days to 0.11/1,000 patient days in the skilled nursing facility. The protective effect of the intervention was statistically significant for both facilities. CONCLUSIONS: Replacement of electronic thermometers with single-use disposables significantly reduced the incidence of C difficile-associated diarrhea in both acute care and skilled nursing care facilities. Data suggest that the rectal route may be important in the transmission of C difficile in these settings.

Aged↗

Laboratory detection of Clostridium difficile. A comparison of media and incubation systems.

Parallel testing for culture recovery of Clostridium difficile was performed using three selective media in each of four anaerobic incubation environmental systems. Testing was completed on 67 stool samples from 60 hospitalized patients in whom C difficile-associated diarrhea was suspected. Three different media were evaluated: CCFA (modified cycloserine-cefoxitin-fructose agar), CCFA-PRAS (CCFA, prereduced-anaerobically-sterilized) and CMBA (modified cycloserine-mannitol-blood agar). The incubation systems compared were an anaerobic chamber (Model 800 Anaerobic Environmental System, Anaerobe Systems, San Jose, CA), the anaerobic jar (BBL, Cockeysville, MD), the anaerobic Bio-Bag (BBL), and the anaerobic pouch (BBL). C difficile was found in 16 samples collected from 15 patients. Comparing recovery on the various types of media in all four anaerobic atmospheres, C difficile was recovered on all (64) CCFA plates, 56 of 64 CCFA-PRAS plates, and 43 of 64 CMBA plates (P < .03 comparing CCFA and CMBA). Of the 48 plates in each incubation system that were inoculated with specimens positive for C difficile, the organism was recovered from 43 plates in the anaerobe chamber, 41 incubated in an anaerobe jar, 40 in the Bio-Bag, and 39 incubated in the GasPak pouch, all providing similar recovery of C difficile (P = .08). The CCFA-PRAS and CMBA media demonstrated less inhibition of normal stool flora compared to the CCFA. Overall CCFA that was anaerobically reduced at least 4 hours before use, and contained the original concentration of antimicrobial agents described by George and colleagues, was superior to CMBA for recovery of C. difficile.

Clinical Laboratory Techniques↗

Use of the polymerase chain reaction for the specific and direct detection of Clostridium difficile in human feces.

The polymerase chain reaction was used for the detection of Clostridium difficile, the etiologic agent of antibiotic-associated colitis. An upstream primer identical to a coding region (segment I) of the C. difficile 16S rRNA gene and a downstream primer complementary to a highly conserved region of eubacterial 16S rRNA served to amplify a targeted 270-base-pair fragment of genomic DNA. This technique allowed the detection of as few as 10 C. difficile organisms among 10(6) Escherichia coli bacteria. This level of sensitivity represents a 100-fold increase over that of conventional anaerobic culture. C. difficile was detected in DNA extracted directly from the stools of 23 patients with antibiotic-associated colitis and from those of four patients with diarrhea whose stools had been negative for C. difficile when assessed in a cytotoxicity assay. No amplification products were found in the stools of asymptomatic patients. When detected in stools of symptomatic patients, amplification products of C. difficile were confirmed by Southern blotting with a nonradioactive, horseradish peroxidase-catalyzed, chemiluminescent probing system in which biotin-labeled oligonucleotides were used. This system discriminates between C. difficile and similar organisms, such as Clostridium sordellii and Clostridium bifermentans. The combination of the polymerase chain reaction with enzyme-linked probing results in a faster and more sensitive assay for C. difficile than standard culture.

Base Sequence↗

Acquisition of Clostridium difficile by hospitalized patients: evidence for colonized new admissions as a source of infection.

The frequency of introduction and spread of specific Clostridium difficile strains among hospitalized patients were assessed by serial cultures of patients admitted to a medical-surgical ward with endemic C. difficile-associated diarrhea. Stool cultures were obtained from 634 (94%) of 678 consecutive admissions to the ward (ward admissions), and all C. difficile isolates were typed by restriction endonuclease analysis. Sixty-five ward admissions introduced C. difficile to the ward, and 54 initially culture-negative admissions acquired C. difficile on the ward. Ward admissions hospitalized within the prior 30 days in the medical center were more likely to be culture-positive for C. difficile at admission to the study ward than those not previously hospitalized at the institution (16% vs. 7%, P less than .001). Nosocomial acquisition of a C. difficile strain was preceded by a documented introduction of that strain to the ward by another asymptomatic ward admission in 16 (84%) of 19 instances, suggesting that C. difficile-colonized new admissions are a major source of nosocomial C. difficile infections.

Bacterial Typing Techniques↗

Periprosthetic Clostridium difficile hip abscess imaged with In-111 WBCs.

During a prolonged hospital stay, left hip pain developed in a woman with sickle cell disease and bilateral hip prostheses. In-111 labeled WBC scintigraphy supplemented by Tc-99m SC bone marrow imaging demonstrated abnormal WBC accumulation surrounding the left greater trochanter. Results of surgical exploration showed an abscess involving the pseudocapsule, trochanteric bursa, and periprosthetic cement column. Cultures grew Clostridium difficile, an unusual pathogen in this site.

Abscess↗

Fecal incontinence in hospitalized patients who are acutely ill.

BACKGROUND: Information about fecal incontinence experienced by patients in acute-care settings is lacking. The relationship of fecal incontinence to several well-known nosocomial or iatrogenic causes of diarrhea has not been determined. OBJECTIVES: To determine the cumulative incidence of fecal incontinence in hospitalized patients who are acutely ill, and to ascertain the relationship between fecal incontinence and stool consistency, and between diarrhea and two well-known nosocomial or iatrogenic etiologies of diarrhea: Clostridium difficile and tube feeding. The relationship of fecal incontinence and risk factors for diarrhea associated with C. difficile and tube feeding in hospitalized patients was examined. METHODS: Fecal incontinence, stool frequency and consistency, administration of tube feeding and medications, severity of illness, and nutritional data were prospectively recorded in 152 patients on acute or critical care units of a university-affiliated Veterans' Affairs Medical Center. Rectal swabs and stool specimens from patients were obtained weekly for C. difficile culture. C. difficile culture and cytotoxin assay were performed on diarrheal stools. HindIII restriction endonuclease analysis (REA) was used for typing of C. difficile isolates. RESULTS: In this study, 33% (50/152) of the patients had fecal incontinence. The proportion of total surveillance days with fecal incontinence in these patients was 0.50 +/- 0.06. A greater percentage of patients with diarrhea had fecal incontinence than patients without diarrhea (23/53 [43%] vs. 27/99 [27%]; p = 0.04). Incontinence was more frequent in patients with loose/liquid stool consistency than in patients with hard/soft stool consistency (48/50 [96%] vs. 71/100 [71%]; p < 0.001). The proportion of surveillance days with fecal incontinence was related to the proportion of surveillance days with diarrhea (r = 0.69; p < 0.001) and the proportion of surveillance days with loose/liquid stools (r = 0.64; p < 0.001). Multivariate risk factors for fecal incontinence were unformed/loose or liquid consistency of stool (RR = 11.1; 95% confidence interval [CI] = 2.2, 56.7), severity of illness (RR = 5.7; CI = 2.6, 12.3), and age (RR = 1.1; CI = 1, 1.1). CONCLUSIONS: Fecal incontinence is common in hospitalized patients who are acutely ill, but the condition was not associated with any specific cause of diarrhea. Because loose or liquid stool consistency is a risk factor for fecal incontinence, use of treatments that result in a more formed stool may be beneficial in managing fecal incontinence. However, treatments that slow intestinal transit should be avoided in patients with C. difficile-associated diarrhea.

Acute Disease↗

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.

Anti-Bacterial Agents↗

Potential role of Clostridium difficile as a cause of duodenitis-proximal jejunitis in horses.

Duodenitis-proximal jejunitis (DPJ) is an idiopathic condition in the horse characterized by inflammation and oedema of the duodenum and proximal jejunum. Clinical signs include colic, ileus, depression, fluid accumulation in the small intestine and stomach, and endotoxaemia. The objective of this study was to investigate prospectively the role of Clostridium difficile in this idiopathic disease. Nasogastric reflux from 10 consecutive cases with DPJ and 16 consecutive horses with other causes of nasogastric reflux was cultured for C. difficile, other Clostridium spp., and Salmonella. Toxigenic strains of C. difficile were isolated from 10/10 (100%) of horses with DPJ and 1/16 controls (P<0.0001). No other known pathogenic clostridia were isolated from either group. Results of this study suggest that C. difficile might be an important cause of this syndrome.

Animals↗

Identification of the latex test-reactive protein of Clostridium difficile as glutamate dehydrogenase.

Computer analysis showed that the gene encoding the latex test-reactive protein of Clostridium difficile exhibited high levels of homology with glutamate dehydrogenases from various sources. Further analysis demonstrated that the recombinant protein possessed glutamate dehydrogenase activity. Our results show that the protein that reacts in commercial latex tests for C. difficile is a glutamate dehydrogenase.

Amino Acid Sequence↗

PCR amplification of rRNA intergenic spacer regions as a method for epidemiologic typing of Clostridium difficile.

From January to March 1993, a suspected outbreak of antibiotic-associated diarrhea occurred on a pediatric oncology ward of the Clinical Center Hospital at the National Institutes of Health. Isolates of Clostridium difficile obtained from six patients implicated in this outbreak were typed by both PCR amplification of rRNA intergenic spacer regions (PCR ribotyping) and restriction endonuclease analysis of genomic DNA. Comparable results were obtained with both methods; five of the six patients were infected with the same strain of C. difficile. Subsequent analysis of 102 C. difficile isolates obtained from symptomatic patients throughout the Clinical Center revealed the existence of 41 distinct and reproducible PCR ribotypes. These data suggest that PCR ribotyping provides a discriminatory, reproducible, and simple alternative to conventional molecular approaches for typing strains of C. difficile.

Bacterial Typing Techniques↗

Clostridium difficile toxin-induced colitis after use of clindamycin phosphate vaginal cream.

OBJECTIVE: To report a case of toxin-positive Clostridium difficile-induced colitis (CDIC) after use of clindamycin phosphate vaginal cream. CASE SUMMARY: A 25-year-old postpartum white woman developed multiple watery stools and abdominal cramping on day 6 of therapy with clindamycin vaginal cream for bacterial vaginosis. She received no other concomitant medications. The patient's stool sample was found to be positive for the C. difficile toxin. Due to the costs and risks of standard therapy, we decided to manage the patient supportively. Complete resolution of the diarrhea occurred shortly thereafter. DISCUSSION: No published clinical studies in patients receiving clindamycin vaginal cream for bacterial vaginosis have documented C. difficile toxin in stool samples of patients with diarrhea. Approximately 5-6% of intravaginal clindamycin is absorbed in the bloodstream, making systemic effects possible. CONCLUSIONS: This report indicates clindamycin phosphate vaginal cream as the most probable cause of CDIC due to the temporal relationship between the occurrence of diarrhea and clindamycin administration, lack of concomitant medications, and documentation of C. difficile toxin.

Adult↗

Ramoplanin: a lipoglycodepsipeptide antibiotic.

OBJECTIVE: To review the pharmacology, antimicrobial activity, pharmacokinetics, clinical applications, and safety of ramoplanin, a lipoglycodepsipeptide antibiotic. DATA SOURCES: Information was obtained from MEDLINE and BIOSIS databases (1984-August 2004) and Oscient Pharmaceuticals using the key words ramoplanin, A 16686, A 16686A, and MDL 62198. STUDY SELECTION AND DATA EXTRACTION: Available English-based articles and abstracts were reviewed, along with information from Oscient Pharmaceuticals. DATA SYNTHESIS: Ramoplanin exerts its bactericidal activity against gram-positive aerobic and anaerobic bacteria by blocking peptidoglycan synthesis via lipid II. In vitro susceptibility reports have demonstrated efficacy against antibiotic-resistant gram-positive pathogens. Cross-resistance has not been documented with vancomyin and other glycopeptides. Clinical trials are investigating ramoplanin's oral administration for treatment of Clostridium difficile-associated diarrhea. Previous clinical trials had evaluated the suppression of colonization of vancomycin-resistant Enterococcus with ramoplanin. Adverse effects are minimal, and drug-drug interactions have not been documented. CONCLUSIONS: The completion of clinical trials will determine whether ramoplanin has a promising role as a treatment option for diarrhea due to C. difficile.

Adult↗