Clostridium Difficile Toxin Assay Research Articles

CLOSTRIDIUM DIFFICILE COLITIS MIMICKING ACUTE APPENDICITIS!

Pseudomembranous colitis associated with Clostridium difficile rarely manifests as an acute abdomen and even more rarely as an acute abdomen without abnormal radiological studies. We are presenting a case of 71-year-old female nursing home resident who was sent to the emergency department for evaluation of fever and dysuria. Review of systems was unremarkable. Patient was started on gatifloxacin for a possible urinary tract infection. However, she soon developed abdominal pain. On physical examination, she was febrile with temperature of 103°F and tachycardiac. Abdominal examination revealed a significant right lower quadrant tenderness with signs of peritoneal irritation. Her white count was surprisingly normal (8700 cells/mcl). A presumptive diagnosis of acute appendicitis was made. CT scan of her abdomen at this time was normal. In view of her clinical signs and symptoms and suspicion of a possible appendicitis, urgent exploratory laprotomy was performed. The laprotomy was essentially benign with no evidence of appendicitis or intestinal perforation. A plasma Clostridium difficile toxin assay sent during hospitalization was found to be positive. She was started on metronidazole postoperatively and showed dramatical improvement over next 48 hours. Patient had a follow up colonoscopy, which showed diffuse pseudomembranes with typical histologic lesions. Cultures of the colonic tissue sample grew clostridium difficile. Pseudomembranous colitis may present as acute abdomen mimicking bowel perforation or peritonitis and in our case as acute appendicitis. Emergency colonoscopy maybe useful for diagnosis and treatment especially when there are no radiological signs. Treatment with metronidazole is effective. Colitis due to C. difficile should be considered in the differential diagnosis of acute abdomen in patients treated with prior antibiotics or living in nursing homes. A high index of suspicion is the key.

Do infection control measures work for methicillin-resistant Staphylococcus aureus?

To review evidence regarding the effectiveness of control measures in reducing transmission of methicillin-resistant Staphylococcus aureus (MRSA) in hospitals. Literature review and surveillance cultures of hospitalized patients at high risk for MRSA colonization or infection. A 500-bed, university-affiliated, community teaching hospital. The percentage of nosocomial S. aureus infections caused by MRSA increased significantly between 1982 and 2002, despite the use of various isolation and barrier precaution policies. The apparent ineffectiveness of control measures may be due to several factors including the failure to identify patients colonized with MRSA. For example, cultures of stool specimens submitted for Clostridium difficile toxin assays at one hospital found that 12% of patients had MRSA in their stool, and 41% of patients with unrecognized colonization were cared for without using barrier precautions. Other factors include the use of barrier precaution strategies that do not account for multiple reservoirs of MRSA, poor adherence of healthcare workers (HCWs) to recommended barrier precautions and handwashing, failure to identify and treat HCWs responsible for transmitting MRSA, and importation of MRSA by patients admitted from other facilities. Control programs that include active surveillance cultures (ASCs) of high-risk patients and use of barrier precautions have reduced MRSA prevalence rates and have been cost-effective. Using a staged approach to implementing ASCs can minimize logistic problems. MRSA control programs are effective if they include ASCs of high-risk patients, use of barrier precautions when caring for colonized or infected patients, hand hygiene, and treating HCWs implicated in MRSA transmission.

Clostridium difficile toxin and faecal lactoferrin assays in adult patients

Clostridium difficile is the primary aetiological agent of antibiotic-associated diarrhoea. The faecal lactoferrin (FL) assay is a simple in vitro test which is highly sensitive to the presence of a marker of polymorphonuclear cells. We evaluated the use of the FL assay in conjunction with the C. difficile toxin assay in faecal samples obtained from 231 adult patients. The relationship between C. difficile toxin and FL in both negative and positive status was highly significant statistically ( P < 0.001). Therefore, the FL assay performed simultaneously with the C. difficile toxin assay can help rule out asymptomatic carriage of C. difficile.

Clostridium difficile infection is a risk factor for bacteremia due to vancomycin-resistant enterococci (VRE) in VRE-colonized patients with acute leukemia.

A cohort study was conducted in a cancer center to identify risk factors for bacteremia with vancomycin-resistant enterococci (VRE) in neutropenic cancer patients colonized with VRE. There were 10 patients with VRE bacteremia among 56 colonized with VRE, of whose charts 51 were available for review. One hundred percent of patients with VRE bacteremia (10 of 10) vs. 56% of patients without VRE bacteremia (23 of 41) had acute leukemia (P = .01, Fisher's exact test). Four of the 10 patients with VRE bacteremia had a positive Clostridium difficile toxin assay within 6 days of their first positive VRE blood culture. Both C. difficile infection and antimicrobial (vancomycin and ciprofloxacin) use during VRE colonization were significant risk factors for VRE bacteremia in univariate analysis. When a Cox proportional hazards model was used to account for differences in follow-up time, C. difficile infection was the only statistically significant risk factor (risk ratio, 8.2; P = .007) for VRE bacteremia in VRE-colonized patients with acute leukemia.

Surgical antibiotic prophylaxis and Clostridium difficile toxin positivity.

To examine a possible relationship between prophylactic antibiotic therapy (PAT) and the development of Clostridium difficile toxin (CDT) positivity. Retrospective case-control study. Tertiary care medical center in New York, NY. A total of 357 patients, admitted from November 1992 to April 1994, with positive. CDT assays. Of these, 23 patients (6%) received only PAT for elective surgical procedures. Thirty-nine patients were matched as controls for age, sex, and surgical procedure. Both CDT positivity and inappropriate use of PAT. Appropriate PAT was used in 26 (42%) of 62 patients (17% cases, 56% controls). The Mantel-Haenszel estimator for the summary odds ratio for the development of CDT positivity from inappropriate use of PAT was 5.1 (95% confidence interval, 1.10 to 23.64). Main duration between the operation and the final antibiotic dose was significantly longer in the CDT-positive group compared with the control group (3.1 vs 1.7 days, P < .05). The length of hospital stay was significantly longer in the CDT-positive group compared with the control group (16.5 vs 10.2 days, P < .05). The prolonged use of PAT in elective surgical cases increases the risk of developing CDT positivity. The appropriate use of PAT could significantly reduce health costs by eliminating unnecessary doses of antibiotics, by decreasing the rate of CDT positivity, and by shortening the hospital stay. Restrictive policies may need to be implemented to prevent further antibiotic misuse.

The challenge of vancomycin-resistant enterococci: A clinical and epidemiologic study

Background: Vancomycin-resistant enterococci have been recovered with increasing frequency from hospitalized patients. Risk factors, mode of nosocomial transmission, extent of colonization in hospitalized patients, and treatment options for these organisms have not been completely delineated. Methods: We studied 53 patients (group A) with vancomycin-resistant enterococci isolated from various clinical specimens and also surveyed for vancomycin-resistant enterococci in stool specimens submitted for Clostridium difficile toxin assays (group B). Stool specimens submitted for identification of bacterial pathogens and stool specimens from hospital employees were also analyzed for vancomycin-resistant enterococci. Results: Seventy-six isolates of vancomycin-resistant enterococci were recovered in group A. Five of these patients harbored vancomycin-resistant enterococci on admission. Fifty-three of 289 group B stool specimens submitted for C. difficile toxin assays yielded vancomycin-resistant enterococci. Cephalosporins and vancomycin were the most common antimicrobial agents received by both groups of patients. Enterococcus faecium isolates were more resistant than Enterococcus faecalis isolates to antimicrobial agents. All isolates exhibited high-level aminoglycoside resistance and were not β-lactamase producers. There were at least 15 different molecular clones of E. faecium and three of E. faecalis. Vancomycin-resistant enterococcal bacteremia was associated with a 100% in-hospital mortality rate. Conclusions: Multidrug-resistant and vancomycin-resistant enterococci have become important nosocomial pathogens that are difficult to treat. Vancomycin-resistant enterococcal bacteremia was associated with a poor prognosis. We found a high rate of colonization in patients with suspected C. difficile toxin colitis. Judicious use of vancomycin and broad-spectrum antibiotics is recommended, and strict infection control measures must be implemented to prevent nosocomial transmission of these organisms.

Fecal leukocytes in stool specimens submitted for Clostridium difficile toxin assay

To determine their diagnostic utility, fecal leukocytes were sought by methylene blue stain in 502 consecutive stool specimens submitted for Clostridium difficile toxin assay. In addition, the stability of fecal leukocytes was assessed by daily examination of 23 stool specimens stored at 4°C and room temperature. The sensitivity, specificity, and positive and negative predictive values of fecal leukocytes in predicting C. difficile toxin assay results were 28%, 92%, 27%, and 93%, respectively. At 4°C, fecal leukocytes retained morphology for a minimum of 3 days. Leukocytes survived as long in stool specimens containing either C. difficile toxin or an enteric pathogen as they did in stool specimens with neither finding. We conclude that testing stool specimens for fecal leukocytes is not useful for predicting the presence of C. difficile toxin, because 72% of stool specimens positive for C. difficile toxin are negative for fecal leukocytes despite their stability.

Inappropriate Testing for Diarrheal Diseases in the Hospital

To assess the degree to which routine stool cultures, ova and parasite examinations, and Clostridium difficile toxin assays may be inappropriately ordered on hospitalized patients, we conducted a retrospective study to determine the relative yield of these tests on specimens collected from outpatients and inpatients as a function of time after admission. During a 3-year period, only 1 of 191 positive stool cultures and none of the 90 ova and parasite examinations with positive results were from the group of patients who had stool specimens submitted after 3 days of hospitalization. Analysis of laboratory work load for a 1-year period showed that specimens from this patient group contributed nearly 50% of the more than 3000 specimens received each year. In contrast, approximately 25% (range, 17% to 33%) of samples, regardless of admission status, were positive for C difficile toxin. Eliminating routine stool cultures and ova and parasite examinations on hospitalized patients would significantly reduce hospital and patient costs without altering patient care. Nationwide, such a policy might achieve a cost savings of +20 to +30 million per year.

Diarrhea in tube-fed patients: Feeding formula not necessarily the cause

PURPOSE: This study of diarrhea in tube-fed patients was undertaken to determine the proportion of cases in which feeding formula is not responsible for the diarrhea, the causes other than the feeding formula, and the diagnostic approach to diarrhea in tube-fed patients. patients and methods: Inpatients at the Truman Memorial Veterans Hospital who received nasoenteric feeding during the time period from October 1986 through May 1988 were eligible for this study. Of 123 patients who received nasoenteric feeding, 32 patients had documented diarrhea (greater than 500 mL per day for at least two consecutive days) and were enrolled. Three of these patients received hypertonic feeding formula, whereas the remaining 29 received isotonic feeding formula. Prospective determinations of the causes of diarrhea were performed. Laboratory tests included fecal leukocytes, stool osmolality, stool electrolytes, and Clostridium difficile toxin assay. Diarrhea was considered osmotic if the stool osmotic gap was greater than 100 mmol/L. Clinical management involved reducing or stopping the feeding formula, stopping suspected medications, or administering appropriate antibiotics. results: There were 32 episodes of diarrhea in tube-fed patients during the study period. A single cause could be specified in 29 cases. The tube feeding formula was responsible for diarrhea in only 21% of these cases. Medications were directly responsible in 61% and C. difficile in 17% of cases. Stool osmotic gap correctly distinguished osmotic from non-osmotic diarrhea in all cases. conclusion: When diarrhea develops in properly tube-fed patients, the feeding formula is usually not responsible for the diarrhea. Patients receiving nasoenteric tube feeding are frequently placed on liquid forms of medications. Many medicinal elixirs contain sorbitol, which is often the cause of diarrhea in tube-fed patients. Review of the medications and determination of the stool osmotic gap are the initial diagnostic steps of highest yield.

A role for colonic stasis in the pathogenesis of disease related to Clostridium difficile.

The records of 133 consecutive patients (65 men, 68 women; age range, 15 months to 88 years; median, 57 years) with either a positive Clostridium difficile stool culture or toxin assay from 1982 to 1984 were reviewed in order to assess the pattern of this disease in a large hospital and to examine the type of patient at risk. All patients had diarrhea and/or bloody stools (121 and 36, respectively). Less specific symptoms were common. Most patients had been exposed to multiple antibiotics, but of those who had received only one agent, cephalosporins were most common (21/43). Nineteen patients had cancer chemotherapy. C. difficile toxin assay was positive in 106, culture was positive in 74, and pseudomembranes were seen in six of the 39 patients who underwent endoscopy. Treatment consisted of stopping antibiotic therapy alone (86 percent response), oral vancomycin (88 percent response) or metronidazole (82 percent response). The overall mortality rate was 23 percent, due to C. difficile colitis in three of 31 cases. Many patients were receiving medications or had other diseases associated with fecal stasis. There is much circumstantial evidence to support a role for fecal stasis in the pathogenesis of C. difficile disease. Patients predisposed to colonic stasis who are receiving antibiotics should be considered at risk for this disease, and preventative measures should be taken to decrease stool transit times.

The significance of quantitative results of C. difficile cultures and toxin assays in patients with diarrhea.

The clinical courses of 114 patients with positive Clostridium difficile cultures or toxin assays performed between 1981 and 1984 were reviewed to determine the relationship between outcome of treatment and quantitative bacteriologic test results. C. difficile culture was positive in 60 of 91 patients while toxin assay was positive in 99 of 114. One third of the patients received supportive therapy only, and 30 percent of these failed to resolve their symptoms. Ninety-one percent of the patients treated with vancomycin resolved, although 11 percent of these suffered relapse. Patients with high toxin titers receiving supportive treatment alone showed a lower response rate than patients with lower toxin titers. This effect was not seen in patients treated with specific therapy nor with different culture quantities. C. difficile colitis has a range of clinical and microbiologic manifestations. Endoscopy is not always diagnostic, both culture and toxin assays are needed for diagnosis, and toxin titer may help in planning treatment. Patients with low toxin titers may be treated supportively, but high toxin titers are an indication for specific therapy. Quantitative culture results have little diagnostic or therapeutic value.

Increased risk of illness among nursery staff caring for neonates with necrotizing enterocolitis.

In 1983 an outbreak of necrotizing enterocolitis (NEC) and hemorrhagic gastroenteritis occurred in our newborn nurseries. Eleven children were ill and three required bowel resections. During the outbreak many of the medical and nursing staff in the nurseries also were ill, prompting a microbiologic and epidemiologic investigation. Bacterial and viral cultures, Clostridium difficile toxin assays, enzyme-linked immunosorbent assays for viral antigens and immunoelectron microscopy of stools identified no associated pathogen. However, using a method of calculating relative risk as an incidence density ratio, we found that nurses who had cared for ill infants were at higher risk for sick call within the 9 days following exposure than nurses who had cared for babies without NEC (relative risk, 1.96; P = 0.05). These results provide additional evidence that a transmissible agent may be responsible for some cases of NEC and support the recommendation for infection control measures during outbreaks. The epidemiologic methods used in this study may be useful in prospective studies of NEC and may help to provide further clues to the cause of this disease.

1087 USE OF A MICOCOMPUTER IN A DIAGNOSTIC VIROLOGY LABORATORY

Aseries of computer programs was developed using an existing data base management system (KnowledgeMan) on a microcomputer to assist with the management of a diagnostic virology lab. The primary purpose was to handle the daily routine: recording specimens and patient data, generating worksheets for the reading and processing of cultures, retrieving culture results or current status, and printing final report forms. It can also handle other lab procedures: Chlamydia cultures, Clostridium difficile toxin assays, and some serologic testing. In addition, the computer facilitates surveillance studies. It can rapidly generate a list of cultures or results for user-defined conditions: ages, hospital location, dates, or a variety of other parameters. A statistics package is included for simple analyses. Security of patient data is always a concern with computer use because of the ease of transporting large volumes of information on floppy disks. Security is provided by KnowledgeMan. All information is stored in scrambled form within files, and cannot be read if accessed from outside KnowledgeMan. On entering the system, each user is assigned a priority status. Each data type, e.g. name, age, result, is assigned up to 16 different access codes to restrict the user to certain pieces of information. The series of programs is menu-driven, and requires no computer knowledge by lab personnel. A computer can decrease significantly the paperwork done by hand, file large amounts of information in a small space, facilitate epidemiologic surveys, and provide a rapid review and analysis of the work performed by the laboratory.