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Hospital-acquired Clostridium difficile infection amongst ICU and burn patients in Kuwait.

OBJECTIVES: To prospectively study the prevalence of nosocomially acquired Clostridium difficile, a major cause of diarrhoea in hospitalized patients, in the intensive care units (ICUs) and burn unit (BUs) of three teaching hospitals in Kuwait. METHODS: During a 1-year prospective study, stool/rectal swabs were obtained from 344 patients admitted into the ICUs of Mubarak Hospital (ICU-1), the Kuwait Cancer Control Centre (ICU-2), and the BU of Ibn Sina Hospital. The presence of C. difficile and/or its toxin was detected by serially culturing the specimens on differential, selective and enriched media and the use of TOX-A/B test, on admission and at subsequent 1-weekly interval until discharge. RESULTS: Out of the 344 patients admitted into these units, over a study period of 1 year, only 263 (77%) were evaluable. All of them had negative stool culture/toxin on admission. Overall, 25 (9.5%) of these 263 patients acquired C. difficile during their hospitalization. Thirteen (7%) of 187 patients acquired C. difficile in ICU-1, 9 (36%) of 25 on ICU-2 and 3 (5.9%) of 51 patients in BU. Eight (32%) developed diarrhoea attributable only to C. difficile and/or toxin, and the remaining 17 (68%) were asymptomatic: none had pseudomembranous colitis. The diarrhoea in these patients was associated with antibiotic use, the main trigger-antibiotics being the third-generation cephalosporins. Acquisition occurred within 4-53 days of admission, with the majority occurring in the first 15 days. CONCLUSION: Overall, the prevalence of hospital-acquired C. difficile infection/colonization was less than 10%. The use of third-generation cephalosporins was high and was related to the development of diarrhoea. Once acquired, diarrhoea developed in about one third of C. difficile-positive cases, an indication that C. difficile infection/colonization endemic in the hospital ICUs studied is usually transmitted among the hospitalized patients.

Adolescent↗

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↗

Clostridium difficile infection in patients discharged from US short-stay hospitals, 1996-2003.

US hospital discharges for which Clostridium difficile-associated disease (CDAD) was listed as any diagnosis doubled from 82,000 (95% confidence interval [CI] 71,000-94,000) or 31/100,000 population in 1996 to 178,000 (95% CI 151,000-205,000) or 61/100,000 in 2003; this increase was significant between 2000 and 2003 (slope of linear trend 9.48; 95% CI 6.16-12.80, p = 0.01). The overall rate during this period was severalfold higher in persons >65 years of age (228/100,000) than in the age group with the next highest rate, 45-64 years (40/100,000; p < or = 0.001). CDAD appears to be increasing rapidly in the United States and is disproportionately affecting older persons. Clinicians should be aware of the increasing risk for CDAD and make efforts to control transmission of C. difficile and prevent disease.

Adolescent↗

Conditions associated with leukocytosis in a tertiary care hospital, with particular attention to the role of infection caused by clostridium difficile.

Few modern studies have enumerated the conditions associated with leukocytosis. Our clinical experience has implicated Clostridium difficile infection in a substantial proportion of patients with leukocytosis. In a prospective, observational study of 400 inpatients with WBC counts of >/=15,000 cells/mm(3), we documented >/=1 infection in 207 patients (53%). Of these 207 patients, 97 (47%) had pneumonia, 60 (29%) had urinary tract infection, 34 (16%) had soft-tissue infection, and 34 (16%) had C. difficile infection. C. difficile infection was present in 25% of patients with WBC counts of >30,000 cells/mm(3) who did not have hematological malignancy. Other causes of leukocytosis in the 400 patients included physiological stress, in 152 patients (38%); medications or drugs, in 42 (11%); hematological disease, in 22 (6%); and necrosis or inflammation, in 22 (6%). C. difficile infection is a prominent cause of leukocytosis and this diagnosis should be considered for patients with WBC counts of >/=15,000 cells/mm(3), even in the absence of diarrheal symptoms.

Adult↗

Clinical manifestations, treatment and control of infections caused by Clostridium difficile.

Clostridium difficile should be suspected in patients who present with nosocomial diarrhoea. It is more common in the elderly or in patients with a debilitating underlying condition who have received antimicrobial agents, and up to 20-25% of patients may experience a relapse. The reference method for diagnosis is the cell culture cytotoxin test which detects the presence of toxin B in a cellular culture of human fibroblasts, but recovering C. difficile in culture allows the performance of a ''second-look" cell culture assay that enhances the potential for diagnosis. Oral metronidazole (500 mg tid or 250 mg every 6 hrs) and oral vancomycin (125 mg every 6 hrs) administered for 1014 days have similar therapeutic efficacy, with response rates near 90-97%. C. difficile strains resistant to metronidazole and with intermediate resistance to vancomycin have been described. The administration of probiotics such as Saccharomyces boulardii, Lactobacillus sp. or brewer's yeast for prophylaxis of CDAD remains controversial.

Anti-Bacterial Agents↗

Impact of a piperacillin-tazobactam shortage on antimicrobial prescribing and the rate of vancomycin-resistant enterococci and Clostridium difficile infections.

UNLABELLED: States in 2002 on antimicrobial prescribing and associated rates of vancomycin-resistant enterococci (VRE) and Clostridium difficile infections.Design. Retrospective chart review.Setting. University-affiliated medical center. Measurements and Main Results. Microbiologic reports, patient demographics, and antimicrobial utilization were evaluated for patients admitted 6 months before the shortage (March 1-August 31, 2001) and for 6 months during the shortage (March 1-August 31, 2002). Significant increases in usage of alternative mu-lactamase inhibitor combinations, cefepime, levofloxacin, vancomycin, clindamycin, and metronidazole were observed during the shortage; in contrast, a significant decrease in the use of ceftriaxone took place. No change in the rate of VRE infection was observed from before to during the piperacillin-tazobactam shortage. However, a paradoxical 47% decrease in the rate of C. difficile colitis was documented during the shortage. Subsequent multivariate analyses suggested the reduced use of ceftriaxone and increased use of levofloxacin, but not the reduced use of piperacillin-tazobactam, correlated with the decreased rate of C. difficile infections. CONCLUSION: The piperacillin-tazobactam shortage was associated with significant changes in antimicrobial prescribing, which resulted in a significant reduction in the rate of C. difficile but not VRE infections.

Anti-Bacterial Agents↗

Autoantibodies to colon in germfree rats monocontaminated with Clostridium difficile.

Germfree rats monocontaminated with the anaerobic microorganisms Clostridium difficile or another Clostridium species (strain G 62) produce auto-antibodies to colon antigen. The antigen can be extracted with phenol water from the feces of germfree rats. Antibodies, demonstrable by means of passive hemagglutination of antigen sensitized sheep erythrocytes appear after monocontamination for 35 days or longer. The indirect immunofluorescence techniques, applied to sections of germfree rat colon, gave positive mucosal staining. The staining was similar to that obtained with sera from patients with ulcerative colitis or from rats immunized with rabbit colon. No antibodies were found in the sera of germfree rats, germfree rats monocontaminated with various other bacteria, conventional rats of germfree origin, or conventional Sprague-Dawley rats. Although the anti-colon antibodies of the Clostridium infected rats reacted with the same feces extract as the antibodies of ulcerative colitis patients or of rabbit colon immunized rats, their specificity was different. While the latter cross-react with polysaccharide from E. coli O14, those from the Clostridium-infected exgermfree rats did not. Rats monocontaminated with Cl. difficile also developed antibodies to this organism, but no cross-reaction between Cl. difficile antigen and colon antigen could be demonstrated. This speaks against breakage of tolerance by cross-reacting bacterial antigen as the cause of autoimmunity in these rats. Other possible mechanisms for autoantibody production in this model are immunogenic alteration of gastrointestinal mucins by bacterial degradation, adjuvant effects of bacterial products, or both.

Animals↗

Investigation of an outbreak of Clostridium difficile infection in a general hospital by numerical analysis of protein patterns by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

One hundred forty-five cultures of Clostridium difficile, including strains from an apparent nosocomial outbreak of infection, were characterized by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis of whole-cell proteins. Each protein pattern was characterized by the presence of one to three dense bands which were highly reproducible. The first 100 strains (in chronological order) were used as the basis for a numerical analysis which divided the strains into 17 phenons (EP types 1 to 17). The protein patterns of the remaining 45 strains were identified to type by comparing their individual patterns against a data base made up of the protein patterns of the first 100 strains. EP type 1 was the most common, with 70 of 139 (50%) patient isolates having this pattern type, and it accounted for 26 of 35 strains (74%) from patients in a medical teaching ward from which the outbreak was believed to have originated. This type was also found as a high proportion of isolations in a number of other medical and oncology wards, but the majority of these isolates occurred subsequent to the isolations on the initial outbreak ward. This technique can therefore provide a method for tracing the possible spread of epidemic strains in hospitals and other institutions and may contribute to a better understanding of the epidemiology of C. difficile.

Adolescent↗

Clostridium difficile infection in patients with haematological malignant disease. Risk factors, faecal toxins and pathogenic strains.

Two hundred and forty-eight patients from shared oncology and general medical wards were prospectively studied over a 6-month period for carriage of Clostridium difficile during an outbreak of clinical disease with an epidemic strain of the organism. Risk factors for infection were assessed. Acute leukaemia and/or its treatment were identified as significantly increasing the risk of infection. The relationship between the type of C. difficile isolated (as defined by a typing system based on the incorporation of [35S]methionine into bacterial proteins followed by gel electrophoresis), the presence of faecal toxins A and B and clinical symptoms were analysed. Carriage of the epidemic strain, type X, had a significant association with symptoms amongst oncology patients, with two thirds of these patients having detectable faecal toxin A and one third detectable faecal toxin B. During an outbreak of C. difficile-associated disease, typing the organism and assaying for both faecal toxins in symptomatic patients may be of benefit in determining which patients require specific, urgent treatment.

Adolescent↗

Clostridium piliforme infection in two farm-raised white-tailed deer fawns (Odocoileus virginianus) and association with copper toxicosis.

Necropsy of 2 white-tailed deer fawns who died acutely revealed diarrhea and melena in case No. 1 and no gross changes in case No. 2. Histologically, the livers of both deer displayed multifocal coagulative necrosis, with infiltrations of neutrophils, macrophages, and lymphocytes. By Warthin-Starry staining, bundles of filamentous bacteria were identified within hepatocytes at the periphery of the necrotic foci in case No. 1. There was multifocal myocardiocyte necrosis in case No. 1 and multifocal lymphoid necrosis of the Peyer's patches in case No. 2. Clostridium piliforme 16S ribosomal ribonucleic acid gene was detected in both livers by polymerase chain reaction (PCR) with C. piliforme-specific primers. The liver copper levels in both cases were normal to slightly elevated. The kidney copper level in case No. 2 was elevated. This represents the first published cases of Tyzzer's disease in deer, a novel use of PCR for the diagnosis of C. piliforme infection, and a possible association between copper toxicosis and Tyzzer's disease.

Animal Diseases↗

CNS Clostridium perfringens infection: a rare complication of preoperative embolization of meningioma.

Gas gangrene is a severe form of gangrene (tissue death) that usually is caused by Clostridium perfringens. It generally occurs at the site of trauma or a recent surgical wound. We report the case of a 45-year-old woman with sphenoid-ridged meningioma who received preoperative transarterial embolization with polyvinyl alcohol. The patient later developed an intratumoral C perfringens infection and died despite intensive medical care. The case represents an extremely rare complication following transarterial embolization of meningioma.

Clostridium perfringens↗

Clostridium perfringens wound infection associated with elastic bandages.

Clostridium perfringens wound infections were associated with the use of nonsterile elastic outer bandages in diabetic patients who had undergone lower extremity amputation for vascular insufficiency. In each case a second surgical procedure was required. Elastic bandages similar to those used in these procedures were found to contain C perfringens and other clostridial species. This report illustrates the need for maintenance of a sterile, nonpermeable inner barrier to prevent transudation of bacteria into the wound and the potential benefit of using sterile elastic outer bandages after amputation for vascular insufficiency.

Aged↗

Molecular epidemiology of endemic Clostridium difficile infection and the significance of subtypes of the United Kingdom epidemic strain (PCR ribotype 1).

We previously identified two subtypes of the epidemic strain Clostridium difficile PCR ribotype 1, one clindamycin-sensitive strain (arbitrarily primed PCR [AP-PCR] type Ia) and a closely related clindamycin-resistant strain (AP-PCR type Ib) in our institution. We have now carried out prospective epidemiological surveillance for 4 years, immediately following the relocation of two acute medicine wards for elderly patients (wards A and B), to determine the clinical epidemiology of subtypes of the epidemic C. difficile PCR ribotype 1 group. To maximize the chance of strain discrimination, we used three DNA fingerprinting methods, AP-PCR, ribospacer PCR (RS-PCR), and pulsed-field gel electrophoresis (PFGE), to analyze C. difficile isolates recovered from symptomatic patients and from repeated environmental samplings. On ward B the incidence of C. difficile infection correlated significantly with the prevalence of environmental C. difficile both in ward areas closely associated with patients and health care personnel (r = 0.53; P < 0.05) and in high-reach sites (r = 0.85; P < 0.05). No such relationships were found on ward A. Seventeen distinct C. difficile genotypes were identified, 17 by AP-PCR, 12 by PFGE, and 11 by RS-PCR, but only 4 of 17 genotypes caused patient infection. Isolates recovered from the hospital ward environment were much more diverse (14 genotypes). AP-PCR type Ia represented >90% of the C. difficile isolates. In addition to this genotype, only two others were isolated from both patient feces and environmental surfaces. AP-PCR type Ib (clindamycin-resistant PCR ribotype 1 clone) was not associated with any cases of C. difficile infection and was isolated from the environment on only two occasions, after having been implicated in a cluster of six C. difficile infections 5 months before this study. The disappearance of this strain implies that differences in virulence and/or selective pressures may exist for this strain and the closely related, widespread C. difficile AP-PCR type Ia strain. Our findings emphasize the need to understand the epidemiology and virulence of clinically significant strains to determine successful control measures for C. difficile infections.

Aged↗