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A ward outbreak of Clostridium difficile enterocolitis
Journal of Infection (I982) 5, 277-282
A ward outbreak
of Clostridium
difficile enterocolitis
R o h i n i L. A b e y e s u n d e r e
Department of Microbiology, St Albans City Hospital, St Albans, Herts Summary Sixteen patients from two wards (total 4 2 beds) developed diarrhoea which was ascribed to infection with Clostridium difficile. This organism and/or its toxin was present in stool samples from fifteen patients. One patient (number one) received prolonged antibiotic therapy, her stool contained Clostridium difficile, and this was the source of infection which spread to the other fifteen patients. Factors contributing to the spread of infection were acute shortage of nursing staff, inadequate hand-washing facilities and inadequately functioning bedpan washers. Introduction P s e u d o m e m b r a n o u s colitis ( P M C ) was described as early as i893 .1 Its occurrence after antibiotic therapy is well knownfl, 3.4 and m o r e recently reports of clustering of cases 5 have pointed to P M C p r o b a b l y being a nosocomial infection transmissible b e t w e e n patients. An outbreak of diarrhoea occurred recently in a 3 o - b e d d e d acute orthopaedic ward (Ward A), and in a r 2 - b e d d e d female surgical w a r d ( W a r d B), as a result of w h i c h it was decided to investigate affected patients for the presence of Clostridium difficile. Laboratory m e t h o d s All stool specimens were cultured at the Public Health L a b o r a t o r y situated at the L u t o n and D u n s t a b l e Hospital, as stools are not routinely screened for CI. difficile at St Albans, nor is cytotoxin testing available. Culture and identification o f C1. difficile T h i s was done b y p-cresol p r o d u c t i o n on a selective medium. 6
C1. difficile cytotoxin test 7 T h e stool is s u s p e n d e d in 3-5 ml o f p h o s p h a t e buffered saline (PBS) containing penicillin and s t r e p t o m y c i n in a bijou bottle and centrifuged for approximately t w e n t y m i n u t e s at 3000 r.p.m, to remove the debris. T h e supernatant is then used for inoculation. Clostridium sordelli antitoxin (Wellcome Laboratories) is diluted one in 50 (one drop to i ml of PBS). T h r e e drops o f diluted antitoxin is a d d e d to one t u b e of the cell line M R C V . T h r e e drops of the supernatant is a d d e d to the cell-line antitoxin t u b e and three drops to another t u b e without antitoxin. T h e caps are tightened and the tubes are incubated on a roller. T h e t u b e s are observed at 24 and 48 hours for the presence of characteristic cytopathic effect and its neutralisation in the antitoxin tube. All specimens were cultured for salmonellae, shigellae and campylobacters. All cultures were negative, as were examination for ova and cysts. o 163-4453/82/o6o277 + 06
$O2.OO/O
© 1982 The British Society for the Study of Infection
278
R.L. ABEYESUNDERE Patients and results
Ward A has 30 beds and is situated on the third floor of a four-storey block. It is of m o d e r n ' race track' design and consists of three four-bedded bays with male and female patients on either side. There are six single rooms, four on the male side and two on the female side of the ward (sixteen male and fourteen female beds). T h e treatment, clean utility, kitchen, dirty utility and sluice rooms are situated along the centre of the ward. T h e large sink in the sluice has a mixer tap with elbow-action hot and cold arms. There are no other hand-washing facilities in the sluice room. T e n patients in Ward A were infected with Cl. difficile (Table I). T h e source of the infection was patient one, who was the first patient to be screened because she had diarrhoea thought to be due to prolonged antibiotic therapy. She was discharged home by the time her stool culture results were known. She was subsequently treated with a course ofmetronidazole when seen as an out-patient. During the following two weeks patients two to five in Ward A developed diarrhoea. As the stool cultures were negative for the usual enteric pathogens and the bedpan washer was constantly out of order, it was decided to screen all patients in Ward A for CI. difficile. At this time patients two to five were being nursed in single rooms in Ward A with enteric precautions. Patient six had diarrhoea within eleven hours of admission to Ward A. She was possibly infected via nurses' hands (Table I). At this point Ward A was closed to all admissions and remained closed for seven weeks. As culture results took two to three days to be completed all patients with diarrhoea were treated with vancomycin (5oo mg six-hourly for fourteen days) after the admission of patient six. Patient four, who had severe diarrhoea, was transferred to an isolation unit. Culture and toxin results showed that a total of ten patients in Ward A had been infected. There were fifteen uninfected patients, six male and nine female, in Ward A at the time of closure. O f the male patients, five were between I8 and 3o years old and had all been involved in traffic accidents. All five used bedpans and four were receiving antibiotics, ampicillin or cephradine. T h e remaining male patient was 7o years old, did not use a bedpan and was not given antibiotics. H e was admitted for exploration of a wound sinus. O f the nine female patients, seven used bedpans and only two of them were receiving antibiotics. O f these one was a 7o-year-old who received flucloxacillin and was persistently constipated, and the other was a 63-year-old who received cotrimoxazole for one week. With the exception of the latter all the uninfected females were in their 7os and had all been admitted for clinical conditions similar to the infected cases, e.g. fractured femur. T w o weeks after Ward A was closed patient one, who had initially been discharged from Ward A, was admitted to Ward B where she was on complete bed rest because of a swollen knee joint. Ward B had eight patients at the time of her admission. T h e fact that she had been re-admitted was not known by the laboratory staff until two days later when a stool specimen was screened for CI. difficile (Table II). She was then given a course ofvancomycin. One week after her admission five patients in Ward B developed diarrhoea. F o u r of the five patients had both toxin- and culture-positive stools and the sample from the other patient (No. I6) gave a non-specific reaction to the toxin test.
Cl. difficile i n f e c t i o n
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Cl. difficile infection
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T h e three uninfected patients in Ward B did not use a bedpan and were not receiving antibiotics. One was a patient with leg ulcers, another was admitted for back pain but was mobile and the third patient was convalescent after surgery. Patient seven in Ward A and patients I3 and 14 in Ward B relapsed in spite of treatment. All three had a return of diarrhoea with recurring cytotoxinpositive stool (Tables I and II). Ward B is situated by itself five hundred yards from Ward A and is a Nightingale ward with fourteen male beds on one side and twelve female beds on the other. T h e sluices are situated at el{her end of the male and female wards and the bedpan washers have only a cold wash cycle. There are no hand-washing facilities in the sluices, the only hand washbasin being situated in the middle of each male and female ward. There was no movement of either nursing or domestic staff between Ward A and Ward B. Only patient one and the medical staff had at times been in both wards. W h e n the circumstances of the outbreak became apparent all patients from Ward B with positive cultures were transferred to Ward A, which was made an isolation ward. Discussion
Only one patient was sigmoidoscoped; biopsy was not done as the rectal mucosa appeared normal. In view of the advanced age of many of the patients and because a number of them were being treated by traction, sigmoidoscopy was not performed. Sigmoidoscopy is not always diagnostic?, 9 T h e rapidity of spread of Cl. difficile in both wards was probably due to a combination of factors. Seventy per cent of patients in Ward A and sixty per cent of patients in Ward B were receiving antibiotics when they were infected. In Ward A there was an acute shortage of nursing staff before the ward was closed. Often there were only three nurses to nurse 28 to 30 patients, the majority of whom were on bed rest or traction. Other factors were the inadequate hand-washing facilities, non-functioning bedpan washers and the advanced age of the patients. T h e excretion of the organism appears to be intermittent. Patients three, eight and 13 each had two negative stools before a positive result was obtained. T h e excretion of the organism and toxin production did not necessarily occur together. Both culture and toxin production were positive in only nine of the sixteen patients. In four patients only cultures were positive, and one patient (number six) had only a toxin-positive stool (Tables I and II). Patient one had both culture- and cytotoxin-positive stool in Ward A (Table I). On admission to Ward B only the organism was isolated. However, all the other patients she infected in this ward had stools that were both organism- and cytotoxinpositive. Patient one either carried two strains or the same strain which in a different environment produced the cytotoxin. P r o m p t treatment with vancomycin probably resulted in the majority of patients having only a few days diarrhoea in spite of their age and clinical condition. Patient three had a bone biopsy for a painful left hip which showed secondary deposits due to an oat cell carcinoma of the lung. H e had diarrhoea only for a few days. Only patients four and five had severe watery diarrhoea. Patient
282
R. L. A B E Y E S U N D E R E
four had vomiting and b r o n c h o p n e u m o n i a , the latter being c o n t r i b u t o r y to her death. Patient five was treated for ten days with vancomycin before her diarrhoea settled. N o n e o f the patients had bloody diarrhoea with the single exception of patient 16 on W a r d B. Cl. difficile was never isolated from her stool. T h e cytotoxin test gave a non-specific reaction. As toxin p r o d u c t i o n cannot be ruled out with such a result the patient was treated purely on clinical grounds. She died of p n e u m o n i a and heart failure post-operatively. Patient IO was interesting in that he never had diarrhoea even t h o u g h subsequent stools showed toxin production. Patient two had a secondary carcinomatous deposit in the acetabulum. She had diarrhoea only for a few days which subsided on s y m p t o m a t i c treatment. She was not treated with metronidazole or vancomycin because she was discharged h o m e before the result of stool examination was known. She h a d one stool screened subsequently which was b o t h cytotoxin- and organism-negative. She remains clinically well. I n order to improve hygiene W a r d B has had proper h a n d - w a s h i n g facilities provided in both male and female sluices and b e d p a n washers with a steam cycle installed. T h e sluice r o o m in W a r d A has had ~ proper h a n d washbasin and a n e w b e d p a n washer with a steam cycle maintaining satisfactory temperature installed. Both wards had their walls washed and were t h o r o u g h l y cleaned before being reopened for admissions. D u r i n g the outbreak £8750 was spent on vancomycin alone. T h i s outbreak o f P M C established b e y o n d d o u b t that Cl. difficile is a hospital p a t h o g e n which can be t r a n s m i t t e d rapidly between patients, and also that v a n c o m y c i n is the most suitable antibiotic for the t r e a t m e n t of P M C . ~° (I am greatly indebted to Dr A. T. Willis, Director of the Luton and Dunstable Public Health Laboratory, for screening innumerable stool specimens. I would also like to thank the following: Dr J. H. Darrell and Dr D. Burnett for helpful advice and criticism; the Consultant Orthopaedic Surgeons for allowing me to use their patients: and Mrs R. Jones for typing the manuscript.) References
I. Finney JMT. Gastro-enterostomy for cicatrizing ulcer of the pulorus. In: Proceedings of the Meeting of February 22nd 1893. Johns Hopkins M e d J I893; 4: 53-55. 2. George WL, Suter VL, Finegold SM. Antimicrobial agent-induced diarrhoea - a bacterial disease. J Infect Dis x977; 136: 822-828. 3. Keating JP, Frank AL, Barton LL, Tedesco FJ. Pseudomembranous colitis associated with ampicillin therapy. Am J Dis Child 1974; I28: 369-370. 4. Gurwith MJ, Rabin HR, Love K. Diarrhoea associated with clindamycin and ampicillin therapy: preliminary results of a co-operative study. J Infect (suppl.) 1977; S xo4-S I I o. 5 Greenfield C, Burroughs A, Szawathowski M, Bass N, Noone P, Pounder R. Is pseudomembranous colitis infectious? Lancet 1981; i: 371-372. 6. Phillips KD, Rogers PA. Rapid detection and presumptive identification of Cl. di~eile by p-cresol production on a selective medium. J Clin Pathol 1981; 34: 642-644. 7. Larson HE, Price HB. Pseudomembranous colitis: presence of clostridial toxin. Lancet x977; ii: 1312-1314. 8. Keighley MRB, Alexander-Williams J, Arabi Yet al. Diarrhoea and pseudomembranous colitis after gastro-intestinal operations. Lancet 1978; ii : I I65-1167. 9. Tedesco FJ. Antibodies associated pseudomembraneous colitis with negative proctosigmoidoscopy examination. Gastroenterology 1979; 77: 295-297. IO. Keighley MRB, Burdon DW, Arabi Yet al. Randomised controlled trial of vancomycin for pseudomembranous colitis and post-operative diarrhoea. Br M e d J x978; ii: i667-I669.
A ward outbreak
of Clostridium
difficile enterocolitis
R o h i n i L. A b e y e s u n d e r e
Department of Microbiology, St Albans City Hospital, St Albans, Herts Summary Sixteen patients from two wards (total 4 2 beds) developed diarrhoea which was ascribed to infection with Clostridium difficile. This organism and/or its toxin was present in stool samples from fifteen patients. One patient (number one) received prolonged antibiotic therapy, her stool contained Clostridium difficile, and this was the source of infection which spread to the other fifteen patients. Factors contributing to the spread of infection were acute shortage of nursing staff, inadequate hand-washing facilities and inadequately functioning bedpan washers. Introduction P s e u d o m e m b r a n o u s colitis ( P M C ) was described as early as i893 .1 Its occurrence after antibiotic therapy is well knownfl, 3.4 and m o r e recently reports of clustering of cases 5 have pointed to P M C p r o b a b l y being a nosocomial infection transmissible b e t w e e n patients. An outbreak of diarrhoea occurred recently in a 3 o - b e d d e d acute orthopaedic ward (Ward A), and in a r 2 - b e d d e d female surgical w a r d ( W a r d B), as a result of w h i c h it was decided to investigate affected patients for the presence of Clostridium difficile. Laboratory m e t h o d s All stool specimens were cultured at the Public Health L a b o r a t o r y situated at the L u t o n and D u n s t a b l e Hospital, as stools are not routinely screened for CI. difficile at St Albans, nor is cytotoxin testing available. Culture and identification o f C1. difficile T h i s was done b y p-cresol p r o d u c t i o n on a selective medium. 6
C1. difficile cytotoxin test 7 T h e stool is s u s p e n d e d in 3-5 ml o f p h o s p h a t e buffered saline (PBS) containing penicillin and s t r e p t o m y c i n in a bijou bottle and centrifuged for approximately t w e n t y m i n u t e s at 3000 r.p.m, to remove the debris. T h e supernatant is then used for inoculation. Clostridium sordelli antitoxin (Wellcome Laboratories) is diluted one in 50 (one drop to i ml of PBS). T h r e e drops o f diluted antitoxin is a d d e d to one t u b e of the cell line M R C V . T h r e e drops of the supernatant is a d d e d to the cell-line antitoxin t u b e and three drops to another t u b e without antitoxin. T h e caps are tightened and the tubes are incubated on a roller. T h e t u b e s are observed at 24 and 48 hours for the presence of characteristic cytopathic effect and its neutralisation in the antitoxin tube. All specimens were cultured for salmonellae, shigellae and campylobacters. All cultures were negative, as were examination for ova and cysts. o 163-4453/82/o6o277 + 06
$O2.OO/O
© 1982 The British Society for the Study of Infection
278
R.L. ABEYESUNDERE Patients and results
Ward A has 30 beds and is situated on the third floor of a four-storey block. It is of m o d e r n ' race track' design and consists of three four-bedded bays with male and female patients on either side. There are six single rooms, four on the male side and two on the female side of the ward (sixteen male and fourteen female beds). T h e treatment, clean utility, kitchen, dirty utility and sluice rooms are situated along the centre of the ward. T h e large sink in the sluice has a mixer tap with elbow-action hot and cold arms. There are no other hand-washing facilities in the sluice room. T e n patients in Ward A were infected with Cl. difficile (Table I). T h e source of the infection was patient one, who was the first patient to be screened because she had diarrhoea thought to be due to prolonged antibiotic therapy. She was discharged home by the time her stool culture results were known. She was subsequently treated with a course ofmetronidazole when seen as an out-patient. During the following two weeks patients two to five in Ward A developed diarrhoea. As the stool cultures were negative for the usual enteric pathogens and the bedpan washer was constantly out of order, it was decided to screen all patients in Ward A for CI. difficile. At this time patients two to five were being nursed in single rooms in Ward A with enteric precautions. Patient six had diarrhoea within eleven hours of admission to Ward A. She was possibly infected via nurses' hands (Table I). At this point Ward A was closed to all admissions and remained closed for seven weeks. As culture results took two to three days to be completed all patients with diarrhoea were treated with vancomycin (5oo mg six-hourly for fourteen days) after the admission of patient six. Patient four, who had severe diarrhoea, was transferred to an isolation unit. Culture and toxin results showed that a total of ten patients in Ward A had been infected. There were fifteen uninfected patients, six male and nine female, in Ward A at the time of closure. O f the male patients, five were between I8 and 3o years old and had all been involved in traffic accidents. All five used bedpans and four were receiving antibiotics, ampicillin or cephradine. T h e remaining male patient was 7o years old, did not use a bedpan and was not given antibiotics. H e was admitted for exploration of a wound sinus. O f the nine female patients, seven used bedpans and only two of them were receiving antibiotics. O f these one was a 7o-year-old who received flucloxacillin and was persistently constipated, and the other was a 63-year-old who received cotrimoxazole for one week. With the exception of the latter all the uninfected females were in their 7os and had all been admitted for clinical conditions similar to the infected cases, e.g. fractured femur. T w o weeks after Ward A was closed patient one, who had initially been discharged from Ward A, was admitted to Ward B where she was on complete bed rest because of a swollen knee joint. Ward B had eight patients at the time of her admission. T h e fact that she had been re-admitted was not known by the laboratory staff until two days later when a stool specimen was screened for CI. difficile (Table II). She was then given a course ofvancomycin. One week after her admission five patients in Ward B developed diarrhoea. F o u r of the five patients had both toxin- and culture-positive stools and the sample from the other patient (No. I6) gave a non-specific reaction to the toxin test.
Cl. difficile i n f e c t i o n
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Cl. difficile infection
281
T h e three uninfected patients in Ward B did not use a bedpan and were not receiving antibiotics. One was a patient with leg ulcers, another was admitted for back pain but was mobile and the third patient was convalescent after surgery. Patient seven in Ward A and patients I3 and 14 in Ward B relapsed in spite of treatment. All three had a return of diarrhoea with recurring cytotoxinpositive stool (Tables I and II). Ward B is situated by itself five hundred yards from Ward A and is a Nightingale ward with fourteen male beds on one side and twelve female beds on the other. T h e sluices are situated at el{her end of the male and female wards and the bedpan washers have only a cold wash cycle. There are no hand-washing facilities in the sluices, the only hand washbasin being situated in the middle of each male and female ward. There was no movement of either nursing or domestic staff between Ward A and Ward B. Only patient one and the medical staff had at times been in both wards. W h e n the circumstances of the outbreak became apparent all patients from Ward B with positive cultures were transferred to Ward A, which was made an isolation ward. Discussion
Only one patient was sigmoidoscoped; biopsy was not done as the rectal mucosa appeared normal. In view of the advanced age of many of the patients and because a number of them were being treated by traction, sigmoidoscopy was not performed. Sigmoidoscopy is not always diagnostic?, 9 T h e rapidity of spread of Cl. difficile in both wards was probably due to a combination of factors. Seventy per cent of patients in Ward A and sixty per cent of patients in Ward B were receiving antibiotics when they were infected. In Ward A there was an acute shortage of nursing staff before the ward was closed. Often there were only three nurses to nurse 28 to 30 patients, the majority of whom were on bed rest or traction. Other factors were the inadequate hand-washing facilities, non-functioning bedpan washers and the advanced age of the patients. T h e excretion of the organism appears to be intermittent. Patients three, eight and 13 each had two negative stools before a positive result was obtained. T h e excretion of the organism and toxin production did not necessarily occur together. Both culture and toxin production were positive in only nine of the sixteen patients. In four patients only cultures were positive, and one patient (number six) had only a toxin-positive stool (Tables I and II). Patient one had both culture- and cytotoxin-positive stool in Ward A (Table I). On admission to Ward B only the organism was isolated. However, all the other patients she infected in this ward had stools that were both organism- and cytotoxinpositive. Patient one either carried two strains or the same strain which in a different environment produced the cytotoxin. P r o m p t treatment with vancomycin probably resulted in the majority of patients having only a few days diarrhoea in spite of their age and clinical condition. Patient three had a bone biopsy for a painful left hip which showed secondary deposits due to an oat cell carcinoma of the lung. H e had diarrhoea only for a few days. Only patients four and five had severe watery diarrhoea. Patient
282
R. L. A B E Y E S U N D E R E
four had vomiting and b r o n c h o p n e u m o n i a , the latter being c o n t r i b u t o r y to her death. Patient five was treated for ten days with vancomycin before her diarrhoea settled. N o n e o f the patients had bloody diarrhoea with the single exception of patient 16 on W a r d B. Cl. difficile was never isolated from her stool. T h e cytotoxin test gave a non-specific reaction. As toxin p r o d u c t i o n cannot be ruled out with such a result the patient was treated purely on clinical grounds. She died of p n e u m o n i a and heart failure post-operatively. Patient IO was interesting in that he never had diarrhoea even t h o u g h subsequent stools showed toxin production. Patient two had a secondary carcinomatous deposit in the acetabulum. She had diarrhoea only for a few days which subsided on s y m p t o m a t i c treatment. She was not treated with metronidazole or vancomycin because she was discharged h o m e before the result of stool examination was known. She h a d one stool screened subsequently which was b o t h cytotoxin- and organism-negative. She remains clinically well. I n order to improve hygiene W a r d B has had proper h a n d - w a s h i n g facilities provided in both male and female sluices and b e d p a n washers with a steam cycle installed. T h e sluice r o o m in W a r d A has had ~ proper h a n d washbasin and a n e w b e d p a n washer with a steam cycle maintaining satisfactory temperature installed. Both wards had their walls washed and were t h o r o u g h l y cleaned before being reopened for admissions. D u r i n g the outbreak £8750 was spent on vancomycin alone. T h i s outbreak o f P M C established b e y o n d d o u b t that Cl. difficile is a hospital p a t h o g e n which can be t r a n s m i t t e d rapidly between patients, and also that v a n c o m y c i n is the most suitable antibiotic for the t r e a t m e n t of P M C . ~° (I am greatly indebted to Dr A. T. Willis, Director of the Luton and Dunstable Public Health Laboratory, for screening innumerable stool specimens. I would also like to thank the following: Dr J. H. Darrell and Dr D. Burnett for helpful advice and criticism; the Consultant Orthopaedic Surgeons for allowing me to use their patients: and Mrs R. Jones for typing the manuscript.) References
I. Finney JMT. Gastro-enterostomy for cicatrizing ulcer of the pulorus. In: Proceedings of the Meeting of February 22nd 1893. Johns Hopkins M e d J I893; 4: 53-55. 2. George WL, Suter VL, Finegold SM. Antimicrobial agent-induced diarrhoea - a bacterial disease. J Infect Dis x977; 136: 822-828. 3. Keating JP, Frank AL, Barton LL, Tedesco FJ. Pseudomembranous colitis associated with ampicillin therapy. Am J Dis Child 1974; I28: 369-370. 4. Gurwith MJ, Rabin HR, Love K. Diarrhoea associated with clindamycin and ampicillin therapy: preliminary results of a co-operative study. J Infect (suppl.) 1977; S xo4-S I I o. 5 Greenfield C, Burroughs A, Szawathowski M, Bass N, Noone P, Pounder R. Is pseudomembranous colitis infectious? Lancet 1981; i: 371-372. 6. Phillips KD, Rogers PA. Rapid detection and presumptive identification of Cl. di~eile by p-cresol production on a selective medium. J Clin Pathol 1981; 34: 642-644. 7. Larson HE, Price HB. Pseudomembranous colitis: presence of clostridial toxin. Lancet x977; ii: 1312-1314. 8. Keighley MRB, Alexander-Williams J, Arabi Yet al. Diarrhoea and pseudomembranous colitis after gastro-intestinal operations. Lancet 1978; ii : I I65-1167. 9. Tedesco FJ. Antibodies associated pseudomembraneous colitis with negative proctosigmoidoscopy examination. Gastroenterology 1979; 77: 295-297. IO. Keighley MRB, Burdon DW, Arabi Yet al. Randomised controlled trial of vancomycin for pseudomembranous colitis and post-operative diarrhoea. Br M e d J x978; ii: i667-I669.