Clostridium difficile colitis associated with chronic renal failure

BACKGROUND: Clostridium difficile-associated diarrhoea (CDAD) is a potentially life-threatening illness which has been shown to be more common and more severe in patients with chronic renal failure (CRF) than in other groups. A review of CDAD in our nephrology unit was carried out. METHODS: A review of microbiology and histology records identified 32 cases of CDAD in the nephrology unit over a 24-month period. Patient notes were reviewed to identify risk factors, clinical features and outcome. Available isolates of C. difficile underwent 16S ribosomal RNA typing. RESULTS: The incidence of CDAD in the nephrology unit was 10.7 per 1000 admissions, compared to 2.7 per 1000 in other areas of the hospital (P<0.0001). CDAD was considered the sole or principal cause of death in six (19%) and was considered a contributing factor in a further seven (22%). Mortality was significantly higher among patients with established CRF (P=0.04). Seven cases occurred as a cluster, over a 1-month period. Isolates from this cluster, along with comparative strains from other areas of the hospital, were found to be PCR type 1. Diarrhoea occurred in 28 (89%) of cases, pyrexia in 17 (53%) and ileus or abdominal pain in 14 (44%). Six patients responded to discontinuation of antibiotics alone and 22 required metronidazole and/or vancomycin. Three patients had colectomy and one caecostomy because of toxic megacolon. Four patients died before specific therapy could be given and in two of these cases the diagnosis was made at autopsy. Twenty-six patients had a record of recent antibiotic therapy. Of these, 15 had at least one agent considered to be inappropriate (excessively broad spectrum agent in 11, excessive duration of therapy in four). Nine patients had only received antibiotics prior to admission. CONCLUSIONS: CDAD carries a high mortality in nephrology patients, especially those with established CRF. The diagnosis may be missed if a careful antibiotic history is not taken, including agents received prior to admission. Rational antibiotic prescribing and adherence to infection control measures are vital to reduce the incidence of this serious condition.     

Single toxin detection is inadequate to diagnose Clostridium difficile diarrhea in pediatric patients

BACKGROUND & AIMS: Clostridium difficile is an important cause of symptomatic diarrhea in pediatric patients. The bacterium produces two toxins, although many laboratories assay for only one. We questioned this diagnostic approach when patients had positive results for C. difficile at our institution, but initially had tested negative at outside laboratories. METHODS: We retrospectively analyzed relative frequencies of C. difficile toxin A alone, toxin B alone, and toxins A and B from pediatric patients with diarrhea. Results were stratified according to toxin detection and patient age. RESULTS: Of 1061 specimens, 276 (26.8%) were positive for C. difficile toxin(s). Fifty-one (18.5%) were positive for toxin A alone, 133 (48.2%) for toxin B alone, and 92 (33.3%) for both toxins. Assaying for toxin B identified C. difficile infection more frequently than did assaying for toxin A (P < 0.0001). The frequency of toxin B detection was significantly higher for older children but not for infants. CONCLUSIONS: Testing for C. difficile toxin A or toxin B alone will result in more frequent misdiagnosis than testing for both toxins. This practice may lead to inappropriate further invasive investigations in children, although this finding may not be applicable to adults.     

Antibacterial activity of teicoplanin against Clostridium difficile

The in vitro inhibitory action of teicoplanin, vancomycin, metronidazole and clindamycin against clinical isolates of Clostridium difficile was investigated. Minimum inhibitory concentrations (MICs) were determined using E test. Teicoplanin (MIC range 0.023-0.75 microgram/ml), vancomycin (MIC range 0.5-3 micrograms/ml) and metronidazole (MIC range 0.19-1 microgram/ml) were all very active against the isolates examined. No resistant strains of C. difficile to those three antimicrobial agents were observed, whereas resistance to clindamycin was found in 39.5% of the tested strains. Teicoplanin was about 4-times more potent than vancomycin. It appears to be a more promising antimicrobial for treatment of C. difficile enteric disease.     

Some aspects of the Clostridium difficile infection

Clostridium difficile is now regarded as the most common nosocomial enteric pathogen. C. difficile infection has a wide spectrum of a clinical presentation ranging from asymptomatic carriage to the fulminant colitis. Antibiotic therapy is the most important risk factor in pathogen contagion, however other factors are also involved. Typical pathophysiology: 1. alteration of the indigenous colonic flora by antibodies, 2. ingestion of spores, 3. colonization by Clostridium difficile, 4. production of its toxins. Both entherotoxin A and cytotoxin B are active in human colon. The mode of action of these toxins is already quite well known. The main treatment includes withdrawal of the inducing agents, supported occasionally by oral Vancomycin and Metronidazole. Relapse is a major complication.     

Physical map of the Clostridium difficile chromosome

The present study was designed to investigate the effect of mercuric chloride administration on copper, zinc, and iron concentrations in the liver, kidney, lung, heart, spleen, and muscle of rats. The results showed that after dose and time exposure to mercuric chloride, the concentration of mercury in the six tissues was significantly elevated. Data showed that there were no interaction between mercury and tissue iron. There was a considerable elevation of the content of copper in the kidney and liver. The most significant changes in the copper concentration took place in the kidneys. About a twofold increase in the copper content of the kidney was noted after exposure to mercuric chloride (3 mg and 5 mg/kg). Only slight elevations in the copper content occurred in the liver especially in high dose and longer exposure time. In the remaining organs, the copper content was not changed significantly (p > 0.05). The most significant changes in the zinc concentration took place in liver, kidney, lung and heart (5 mg/kg). Marked changes in kidney zinc concentrations were observed at any of the specified doses. Zinc concentrations were significantly increased in kidney of rats sacrificed 9-48 h after s.c. injection of HgCl2 (5 mg/kg); in liver obtained from rats at 18, 24 or 48 h after injection; and in lung after 24 or 48 h of treatment. The heart and spleen zinc concentrations were elevated at 24 and 48 h after injection of HgCl2 (5 mg/kg), respectively. The results of this study implicate that effects on copper and zinc concentrations of the target tissues of mercury may play an important role in the pathogenesis of acute mercuric chloride intoxication.