Clostridium difficile-associated diarrhoea - aspects of hospital epidemiology and treatment

University dissertation from Marlene Wullt, Department of Infectious Diseases, University Hospital MAS, SE-205 02 Malmö, Sweden

Abstract: Clostridium difficile is a spore-forming bacterium that causes antibiotic-associated diarrhoea and is responsible for hospital outbreaks of diarrhoea. In the first study, 173 consecutive isolates of C. difficile collected from 147 patients at Malmö University Hospital during 1995 were typed by AP-PCR to determine whether cross-transmission could explain the increased incidence of Clostridium difficile-associated diarrhoea (CDAD) at our hospital. Overall DNA analysis of the combined AP-PCR data yielded 140 types, of which 130 were unique types, whereas 10 common types occurred repeatedly in 33 patients. In eight of these 33 patients epidemiological data confirmed a high probability of nosocomial transmission. Thus, our study suggested a low frequency of nosocomial transmission of CDAD during the study period. In a follow-up study the same C. difficile isolates were examined by PCR-ribotyping, and results were compared with those generated by AP-PCR. PCR-ribotyping demonstrated a somewhat higher rate of nosocomial transmission of C. difficile than shown by AP-PCR. Hospital environments are considered to be one of the most important reservoirs of C. difficile spores. C. difficile spores are resistant to most commonly used disinfecting chemicals. Spores of four strains of C. difficile were tested against isopropanol 70%, glutaraldehyde 2%, peracetyl ions 1.6% and acidified nitrite 0.1M using a dilution-neutralisation method. Peracetyl ions and acidified nitrite showed highly sporicidal activity independently of organic load conditions. Both agents appear to be suitable for the inactivation of C. difficile spores in hospital environments. There are currently few options for the treatment of CDAD. In an investigator-initiated, randomised controlled, double-blind trial 114 patients with an initial episode of CDAD received either fusidic acid or metronidazole. Of the patients in the fusidic acid group 83% were clinically cured in comparison to 93% in the metronidazole group (P=0.116). Bacteriological cure did not differ between the two groups. Clinical and bacteriological recurrences were noted in 27% and 13% respectively of the patients receiving fusidic acid and in 29% and 10% of those given metronidazole. The results indicate that fusidic acid seems to be equally effective to metronidazole in curing an initial episode of CDAD. It is poorly understood why some individuals in particular suffer multiple recurrences of CDAD. The disturbed colonic microflora in these patients is considered as a main cause for recurrent episodes. Biotherapy aims to restore the commensal gut flora and hence prevent colonisation of C. difficile. A double-blind, placebo-controlled trial was initiated by the author to analyse the ability of Lactobacillus plantarum 299v to prevent further recurrent episodes of CDAD. Recurrence of clinical symptoms was seen in four of eleven patients who received metronidazole in combination with L. plantarum 299v and in six of nine treated with metronidazole in combination with placebo. Although the small sample size does not allow any conclusion to be drawn concerning the efficacy of L. plantarum in patients with RCDAD, the results of this trial may contribute to the ongoing discussion about the benefits of probiotics in patients with RCDAD and encourage the performance of larger multicenter studies.

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