- Email: [email protected]
HOSPITAL OUTBREAKS OF CLOSTRIDIUM DIFFICILE
751 HOSPITAL OUTBREAKS OF CLOSTRIDIUM DIFFICILE
SIR,-Dr Bender and colleagues (July 5, p 11) describe an outbreak of Clostridium difficile diarrhoea and their attempts to eradicate the organism. We have experienced a similar outbreak in our institution, and for twelve months after its onset new cases were Such outbreaks have been reported with increasing in recent years.2 The finding that C difficile may be endemic in certain institutions does not in itself explain these events. Some vital factor is required which will transform endemic asymptomatic carriage of the organism to an outbreak of symptomatic infection with diarrhoea and pseudomembranous colitis. We suggest that this factor may be unusual virulence in the strain of C difficile. Testing of this hypothesis must await the wider availability of techniques for C difficile serotyping, but did Bender and colleagues observe a higher incidence of symptomatic infections in patients with nosocomially acquired, as opposed to imported,
diagnosed.1 frequency
C difficile?
Vancomycin, because of its efficacy and despite its cost, is the drug of choice in the treatment of pseudomembranous colitis and C difficile associated diarrhoea,3 and we were surprised that metronidazole, a drug which in our experience and that of others,2 is not reliable in the treatment of this disorder, was used. Reports of metronidazole-induced colitis cast further doubts on its suitability 44 We agree with Bender et al that C difficile is very difficult to eradicate after an outbreak. C difficile is a spore former and heavy environmental contamination has been associated with symptomatic cases.s Eradication will thus mean thorough environmental cleaning besides the treatment of all carriers. Environmental decontamination is difficult to achieve, and the ward may have to be closed. This approach has been successful in terminating outbreaks where other measures had failed.2,6 Department of Clinical Medicine, Trinity College Dublin and Sir Patrick Dun’s Hospital, Dublin, Ireland
1.
R. A. O’CONNOR C. P. KELLY T. N. WALSH D. G. WEIR
of any established correlation between serotype, toxigenic potential, or other virulence factor with clinical expression in terms of colonisation rates or disease severity. An especially virulent strain is conceivable, but is not established in either clinical or experimental animal studies. Among the six patients with nosocomially acquired infections four had diarrhoea, compared with two out of nine among the imported cases. Dr Williams (Aug 9, p 350) asks whether our experience represents a true outbreak or increased surveillance. As reflected in the title of our paper, our belief is that C difficile is endemic among the elderly since 22 % of incoming patients were positive for C difficile toxin. This raises the important issue of the aetiology of infectious diarrhoea in the elderly in general and in nursing homes in particular. Numerous studies have been designed to identify enteric pathogens in select populations (such as infants, gay men, international travellers, and populations of developing countries) but there is sparse information on infectious diarrhoea in the elderly. 11 % of the US population is over age 65 years, and there are now as many nursing home beds in the US as there are hospital beds. A has emphasised how little National Institutes of Health we know about infections in the elderly.’ We hope that the points raised about serotyping, strain variations in virulence, treatment choices, and surveillance methods do not obscure our main theme-namely, the risks of this infection associated with ageing and with nursing homes.
workshop
Johns Hopkins Hospital, Division of Infectious Diseases, Baltimore, Maryland 21205, USA and Geriatric Research, Education and Clinical Center, VA Medical Center, Gainesville, Florida 32602, USA
JOHN G. BARTLETT RICHARD BENNETT BARBARA E. LAUGHON BRADLEY S. BENDER
JG: Treatment of Clostridium difficile colitis. Gastroenterology 1985; 89: 1192-95. 2. Anon. Blue book, 1984-1985. New York: Hearst Corporation, 1984. 3. Viscidi R, Willey S, Bartlett JG. Isolation rates and toxigenic potential of Clostridium difficile isolates from various patient populations. Gastroenterology 1981; 81: 8-9. 4. Schneider EL. Infectious diseases in the elderly. Ann Intern Med 1983; 98: 395-400. 1. Bartlett
Kelly CP, O’Connor R, Weir DG. Pseudomembranous colitis and cefotaxime. Lancet 1986;
i:
102-03.
GCJ, Allen E, Millard PH. Clostridium difficile diarrhoea: a highly infectious organism. Age Ageing 1984; 13: 363-66. 3. Silva J, Batts DH, Fekety R, et al. Treatment of Clostridium difficile colitis and diarrhoea with vancomycin. Am J Med 1981; 71: 815-19. 4. Thompson G, Clark AH, Hare K, et al. Pseudomembranous colitis after treatment with metronidazole. Br Med J 1981; 282: 864-65. 5. Fekety R, Kim KH, Batts DH, et al. Studies on the epidemiology of antibiotic associated Clostridium difficile colitis. Am J Clin Nutr 1980; 33 (suppl): 2527-32. 6. Keighley MR. Antibiotic associated pseudomembranous colitis: Pathogenesis and management. Drugs 1980; 20: 49-56.
2. Bennett
**This letter has been shown to Dr Bartlett and his colleagues, reply follows.-ED. L. SiR,—We appreciate the interest of Dr O’Connor and colleagues and other correspondents in our study. Dr Delmee and Professor Michaux (Aug 9, p 350) express concerns about our use of metronidazole rather than vancomycin. Our rationale for metronidazole was based on cost and efficacy data.1,2 Several studies suggest that the two drugs are therapeutically equivalent for patients who are not seriously ill and that the incidence of post-treatment relapse is about the same. However, the relative costs of the drugs for a 10 day course ($600 vs$10) favour metronidazole. Although metronidazole has been reported to cause colitis the denominator is huge. Vancomycin is rarely given orally for any other condition, but the oral route certainly causes Clostridium difficile disease in hamsters. For serotyping we are using several methods (protein patterns, phage typing, antibiograms, ELISA) but the analysis is not yet complete. Antibiograms, toxin B production, and protein patterns whose
B
many of the isolates have not shown a common pattern. O’Connor et al also asks about the possibility of "a particularly virulent strain of C difficile". Our studies and others have shown substantial variation in toxigenic potential for both toxin A (enterotoxin) and toxin B (cytotoxin).3 However, we are not aware on
SIR,-Dr Bender and colleagues suggest that Clostridium difficile is endemic on chronic care wards, though we are not certain whether the isolation of C difficile from their patients’ stools represented true endemicity or a prolonged outbreak despite enteric precautions. Other investigators1 have shown that the C difficile carriage rate in adults who have neither diarrhoea nor previous antibiotic exposure is low. We have looked for C difficile and its toxin in stool samples from 20 geriatric patients on a long-stay ward. No patient had had C difficile associated diarrhoea in the preceding 12 months, only 1 had received antibiotics in the 4 weeks before the study, and none had gastrointestinal symptoms, including diarrhoea or abdominal pain. Of the stool samples 2 were C difficile culture positive and a further 2 contained C difficile toxin. The 1 patient who had received antibiotics (ampicillin and flucloxacillin) in the preceding month was culture positive. These results confirm the suggestion of Bender et al that C difficile may be endemic in patients on long-stay wards, including patients who have not recently received antibiotics. The findings also suggest that the absence of any abdominal symptoms or previous known cases of pseudomembranous colitis on long-stay wards does not preclude the presence of this organism in such patients. C difficile should therefore be considered in any geriatric patient on a long-stay ward as a potential cause for gastrointestinal symptoms. Pavilion One, Department of Medicine (Geriatrics), Victoria Infirmary, Newcastle upon Tyne NE1 4LP; and Department of Microbiology, University of Newcastle upon Tyne 1. Borriello
SP, Larson HE. Antibiotics
K. W. WOODHOUSE T. S. J. ELLIOTT E. STANSFIELD and
Chemother 1981; 7 (suppl A): 53-62.
pseudomembranous
colitis.
J Antimicrob
SIR,-Dr Bender and colleagues (July 5, p 11) describe an outbreak of Clostridium difficile diarrhoea and their attempts to eradicate the organism. We have experienced a similar outbreak in our institution, and for twelve months after its onset new cases were Such outbreaks have been reported with increasing in recent years.2 The finding that C difficile may be endemic in certain institutions does not in itself explain these events. Some vital factor is required which will transform endemic asymptomatic carriage of the organism to an outbreak of symptomatic infection with diarrhoea and pseudomembranous colitis. We suggest that this factor may be unusual virulence in the strain of C difficile. Testing of this hypothesis must await the wider availability of techniques for C difficile serotyping, but did Bender and colleagues observe a higher incidence of symptomatic infections in patients with nosocomially acquired, as opposed to imported,
diagnosed.1 frequency
C difficile?
Vancomycin, because of its efficacy and despite its cost, is the drug of choice in the treatment of pseudomembranous colitis and C difficile associated diarrhoea,3 and we were surprised that metronidazole, a drug which in our experience and that of others,2 is not reliable in the treatment of this disorder, was used. Reports of metronidazole-induced colitis cast further doubts on its suitability 44 We agree with Bender et al that C difficile is very difficult to eradicate after an outbreak. C difficile is a spore former and heavy environmental contamination has been associated with symptomatic cases.s Eradication will thus mean thorough environmental cleaning besides the treatment of all carriers. Environmental decontamination is difficult to achieve, and the ward may have to be closed. This approach has been successful in terminating outbreaks where other measures had failed.2,6 Department of Clinical Medicine, Trinity College Dublin and Sir Patrick Dun’s Hospital, Dublin, Ireland
1.
R. A. O’CONNOR C. P. KELLY T. N. WALSH D. G. WEIR
of any established correlation between serotype, toxigenic potential, or other virulence factor with clinical expression in terms of colonisation rates or disease severity. An especially virulent strain is conceivable, but is not established in either clinical or experimental animal studies. Among the six patients with nosocomially acquired infections four had diarrhoea, compared with two out of nine among the imported cases. Dr Williams (Aug 9, p 350) asks whether our experience represents a true outbreak or increased surveillance. As reflected in the title of our paper, our belief is that C difficile is endemic among the elderly since 22 % of incoming patients were positive for C difficile toxin. This raises the important issue of the aetiology of infectious diarrhoea in the elderly in general and in nursing homes in particular. Numerous studies have been designed to identify enteric pathogens in select populations (such as infants, gay men, international travellers, and populations of developing countries) but there is sparse information on infectious diarrhoea in the elderly. 11 % of the US population is over age 65 years, and there are now as many nursing home beds in the US as there are hospital beds. A has emphasised how little National Institutes of Health we know about infections in the elderly.’ We hope that the points raised about serotyping, strain variations in virulence, treatment choices, and surveillance methods do not obscure our main theme-namely, the risks of this infection associated with ageing and with nursing homes.
workshop
Johns Hopkins Hospital, Division of Infectious Diseases, Baltimore, Maryland 21205, USA and Geriatric Research, Education and Clinical Center, VA Medical Center, Gainesville, Florida 32602, USA
JOHN G. BARTLETT RICHARD BENNETT BARBARA E. LAUGHON BRADLEY S. BENDER
JG: Treatment of Clostridium difficile colitis. Gastroenterology 1985; 89: 1192-95. 2. Anon. Blue book, 1984-1985. New York: Hearst Corporation, 1984. 3. Viscidi R, Willey S, Bartlett JG. Isolation rates and toxigenic potential of Clostridium difficile isolates from various patient populations. Gastroenterology 1981; 81: 8-9. 4. Schneider EL. Infectious diseases in the elderly. Ann Intern Med 1983; 98: 395-400. 1. Bartlett
Kelly CP, O’Connor R, Weir DG. Pseudomembranous colitis and cefotaxime. Lancet 1986;
i:
102-03.
GCJ, Allen E, Millard PH. Clostridium difficile diarrhoea: a highly infectious organism. Age Ageing 1984; 13: 363-66. 3. Silva J, Batts DH, Fekety R, et al. Treatment of Clostridium difficile colitis and diarrhoea with vancomycin. Am J Med 1981; 71: 815-19. 4. Thompson G, Clark AH, Hare K, et al. Pseudomembranous colitis after treatment with metronidazole. Br Med J 1981; 282: 864-65. 5. Fekety R, Kim KH, Batts DH, et al. Studies on the epidemiology of antibiotic associated Clostridium difficile colitis. Am J Clin Nutr 1980; 33 (suppl): 2527-32. 6. Keighley MR. Antibiotic associated pseudomembranous colitis: Pathogenesis and management. Drugs 1980; 20: 49-56.
2. Bennett
**This letter has been shown to Dr Bartlett and his colleagues, reply follows.-ED. L. SiR,—We appreciate the interest of Dr O’Connor and colleagues and other correspondents in our study. Dr Delmee and Professor Michaux (Aug 9, p 350) express concerns about our use of metronidazole rather than vancomycin. Our rationale for metronidazole was based on cost and efficacy data.1,2 Several studies suggest that the two drugs are therapeutically equivalent for patients who are not seriously ill and that the incidence of post-treatment relapse is about the same. However, the relative costs of the drugs for a 10 day course ($600 vs$10) favour metronidazole. Although metronidazole has been reported to cause colitis the denominator is huge. Vancomycin is rarely given orally for any other condition, but the oral route certainly causes Clostridium difficile disease in hamsters. For serotyping we are using several methods (protein patterns, phage typing, antibiograms, ELISA) but the analysis is not yet complete. Antibiograms, toxin B production, and protein patterns whose
B
many of the isolates have not shown a common pattern. O’Connor et al also asks about the possibility of "a particularly virulent strain of C difficile". Our studies and others have shown substantial variation in toxigenic potential for both toxin A (enterotoxin) and toxin B (cytotoxin).3 However, we are not aware on
SIR,-Dr Bender and colleagues suggest that Clostridium difficile is endemic on chronic care wards, though we are not certain whether the isolation of C difficile from their patients’ stools represented true endemicity or a prolonged outbreak despite enteric precautions. Other investigators1 have shown that the C difficile carriage rate in adults who have neither diarrhoea nor previous antibiotic exposure is low. We have looked for C difficile and its toxin in stool samples from 20 geriatric patients on a long-stay ward. No patient had had C difficile associated diarrhoea in the preceding 12 months, only 1 had received antibiotics in the 4 weeks before the study, and none had gastrointestinal symptoms, including diarrhoea or abdominal pain. Of the stool samples 2 were C difficile culture positive and a further 2 contained C difficile toxin. The 1 patient who had received antibiotics (ampicillin and flucloxacillin) in the preceding month was culture positive. These results confirm the suggestion of Bender et al that C difficile may be endemic in patients on long-stay wards, including patients who have not recently received antibiotics. The findings also suggest that the absence of any abdominal symptoms or previous known cases of pseudomembranous colitis on long-stay wards does not preclude the presence of this organism in such patients. C difficile should therefore be considered in any geriatric patient on a long-stay ward as a potential cause for gastrointestinal symptoms. Pavilion One, Department of Medicine (Geriatrics), Victoria Infirmary, Newcastle upon Tyne NE1 4LP; and Department of Microbiology, University of Newcastle upon Tyne 1. Borriello
SP, Larson HE. Antibiotics
K. W. WOODHOUSE T. S. J. ELLIOTT E. STANSFIELD and
Chemother 1981; 7 (suppl A): 53-62.
pseudomembranous
colitis.
J Antimicrob