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WILL THE REAL CLOSTRIDIUM SPECIES RESPONSIBLE FOR ANTIBIOTIC-ASSOCIATED COLITIS PLEASE STEP FORWARD?
338 After treatment with tetracycline for 7 days, both patients recovered fully. The history of acute diarrhoea before the onset of malabsorption syndrome in our patients and in three out of five of the patients of Roberts et al. suggests that this is probably an important factor in a predisposed host for the development of bacterial malabsorption syndrome. We feel this may be important and see no reason why it should be restricted to adults. of Texas Health Science Center, Houston, Texas 77025, U.S.A.
University
GUILLERMO M. RUIZ-PALACIOS HERBERT L. DUPONT
BACTERIAL OVERGROWTH SYNDROME WITHOUT BLIND LOOP
SIR,-Dr Roberts and his colleagues’ make the important
point that malabsorption due to bacterial contamination of the small bowel can occur in the absence of a demonstrable anatomical abnormality. Their claim that this had not previously been described must, however, be refuted. In 1971 I suggested that the term "contaminated small bowel syndrome" should be used rather than the earlier term "blind loop syndrome", for this very reason.2 Examples include cholangitis where the infected biliary tree acts as a reservoir for bacteria to contaminate the upper gut,3 infants with temporary monosaccharide malabsorption,4 and infants and children with malnutrition.5,6 Princess Margaret Children’s Medical Research Foundation. Perth, Western Australia 6001
MICHAEL GRACEY
SIR,-We also have seen patients with bacterial contamination of the small bowel but no demonstrable anatomical sump.7 Five patients had a specific motor disorder of stomach and small intestine, characterised by absence of the cyclically recurring fronts of propulsive motor activity that are found in all normal individuals. All five had evidence of jejunal bacterial overgrowth, with abnormal 14C-glycocholic-acid breath tests that returned to normal after a 5-day course of antibiotics. A blind loop or organic stenosis was not demonstrable, but one patient had systemic sclerosis and dilated jejunal loops. Although we cannot be certain that the motility disorder caused the bacterial overgrowth in these patients, it might be worth looking for this motility disorder in elderly patients with the syndrome described by Roberts et al. Department of Medical Research, University of Leuven, St. Rafaël, B-3000 Leuven,
Belgium
G. VANTRAPPEN
WILL THE REAL CLOSTRIDIUM SPECIES RESPONSIBLE FOR ANTIBIOTIC-ASSOCIATED COLITIS PLEASE STEP FORWARD?
SIR,-Two recent Lancet papers have noted that stools from patients with antibiotic-associated colitis contain a toxin which is cytopathic in tissue culture.8,9 The cytopathic effects of the toxin were neutralised with Clostridium sordellii antitoxin. The conclusion is that Cl,. sordellii is responsible for antibiotic-associated colitis. 1. 2. 3. 4. 5.
Roberts, S. H., James, O., Jarvis, G. H. Lancet, 1977, ii, 1193. Gracey, M. Gut, 1971, 12, 403. Scott, A. J., Khan, G. A. ibid. 1968, 9, 187. Gracey, M., Burke, V., Anderson, C. M. Lancet, 1969, ii, 384. Gracey, M., Suharjono, Sunoto, Stone, D. E. Am. J. clin. Nutr. 1973, 26,
1170. 6. Heyworth, B., Brown, J. Archs. Dis. Childh. 1975, 50, 27. 7. Vantrappen, G., Janssens, J., Hellemans, J., Ghoos, Y. J. clin. Invest.
59, 1158. 8. Rifkin, G. D., Fekety, F. R., Silva, J. Jr. Lancet, 9. Larson, H. E., Price, A. B. ibid. p. 1312.
1977, ii, 1103.
1977,
Similar results have been noted in our laboratory using Cl. sordellii antitoxin to neutralise colitis toxin. However, we have been reluctant to ascribe a pathogenic role to this organism because Cl. sordellii has not been recovered in stool cultures by us or by others,8,9 because intracoccal injections of reference strains of Cl. sordellii kill hamsters but necropsies reveal no intestinal lesions, and because the cell-free supernatant of toxinproducing Cl. sordellii strains fail to produce cytotoxicity in tissue culture. Wel0,l1 have found another clostridial species which seems to satisfy these criteria. Cultures of stools from patients with antibiotic-associated colitis yielded Cl. difficile, an organism which is rarely encountered in the normal flora of healthy persons. Broth cultures of these isolates injected intracxcally into hamsters caused an enterocolitis which simulates the anatomical features of the disease encountered clinically. Furthermore, the cell-free supernatant of the Cl. difficile isolates are cytopathic in tissue culture and cytotoxicity is neutralised when the broth supernatants of these strains are mixed with either gasgangrene polyvalent antitoxin or Cl. sordellii antitoxin.’ Our conclusion is that Cl. sordellii antitoxin does indeed neutralise the toxin found in stools from patients with antibiotic-associated colitis. However, this may represent antigenic cross-reactivity between clostridial toxins. Other clostridial species may cause this disease, but the weight of evidence strongly supports the pathogenic role of Cl. difficile. Infectious Disease Research Laboratory, Boston Veterans Administration Hospital, and Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts, U.S.A.
JOHN G. BARTLETT TEWEN CHANG ANDREW B. ONDERDONK
TREATMENT OF ANTIBIOTIC-INDUCED COLITIS BY METRONIDAZOLE
SIR,-Rifkin et al.’ and Dr Modigliani and Dr Delchier (Jan. 14, p. 97) described cases of antibiotic-induced colitis which responded rapidly to oral vancomycin. Your editorial2 prompted us to try metronidazole therapy in a case of severe ampicillin-induced colitis. The patient was a 27-year-old woman, without a history of gastrointestinal disease. 3 days before becoming ill, she had finished a 7-day course of ampicillin (2g/day) for bronchitis. She had colicky abdominal pain, frequent bowel movements, vomiting, and fever (40 °C), which were followed by asthenia, anorexia and mild weight loss. Abdominal signs and fever persisted for 10 days before she was admitted. On examination, the patient was moderately dehydrated and had a distended, tender abdomen. Serum-sodium was 125 mmol/l, hxmoglobin was 9 g/dl, and serum-albumin was 2.2 g/dl. Proctosigmoidoscopy showed numerous yellow-white plaques with intervening normal mucosa. Biopsy confirmed the diagnosis of pseudomembranous colitis. Barium enema showed that the whole colonic wall had a thumb-print pattern. Qualitative stool culture revealed Clostridium perfringens, Cl. butyricum, Bacteroides species, and normal aerobic flora. The patient’s general condition improved after 5 days water-electrolyte replacement and low-residue diet, but diarrhoea persisted with 8-10 liquid, malodorous stools per day. After metronidazole (1-3 g/day) was given, this improved to 3,2, and 1 soft stools/day after 24 h, 48 h, and 72 h treatment, respectively. Proctosigmoidoscopy done 7 days later showed a normal mucosa, confirmed by biopsy, and a second barium enema showed a normal mucosal pattern with only light residual motor disturbances. Metronidazole was 10. Bartlett, J. G., Change, T. W., Gurwith, M., Gorbach, S. L., Onderdonk, A. B. New Engl. J. Med. (in the press). 11. Bartlett, J. G., Onderdonk, A. B., Cisneros, R. L., Kasper, D. L. J. infect. Dis. 1977, 136, 701. 1. Rifkin, G. D., Fekety, F. R., Silva, J., Sack, R. B. Lancet, 1977, ii, 1103.
2. ibid. p. 1113.
University
GUILLERMO M. RUIZ-PALACIOS HERBERT L. DUPONT
BACTERIAL OVERGROWTH SYNDROME WITHOUT BLIND LOOP
SIR,-Dr Roberts and his colleagues’ make the important
point that malabsorption due to bacterial contamination of the small bowel can occur in the absence of a demonstrable anatomical abnormality. Their claim that this had not previously been described must, however, be refuted. In 1971 I suggested that the term "contaminated small bowel syndrome" should be used rather than the earlier term "blind loop syndrome", for this very reason.2 Examples include cholangitis where the infected biliary tree acts as a reservoir for bacteria to contaminate the upper gut,3 infants with temporary monosaccharide malabsorption,4 and infants and children with malnutrition.5,6 Princess Margaret Children’s Medical Research Foundation. Perth, Western Australia 6001
MICHAEL GRACEY
SIR,-We also have seen patients with bacterial contamination of the small bowel but no demonstrable anatomical sump.7 Five patients had a specific motor disorder of stomach and small intestine, characterised by absence of the cyclically recurring fronts of propulsive motor activity that are found in all normal individuals. All five had evidence of jejunal bacterial overgrowth, with abnormal 14C-glycocholic-acid breath tests that returned to normal after a 5-day course of antibiotics. A blind loop or organic stenosis was not demonstrable, but one patient had systemic sclerosis and dilated jejunal loops. Although we cannot be certain that the motility disorder caused the bacterial overgrowth in these patients, it might be worth looking for this motility disorder in elderly patients with the syndrome described by Roberts et al. Department of Medical Research, University of Leuven, St. Rafaël, B-3000 Leuven,
Belgium
G. VANTRAPPEN
WILL THE REAL CLOSTRIDIUM SPECIES RESPONSIBLE FOR ANTIBIOTIC-ASSOCIATED COLITIS PLEASE STEP FORWARD?
SIR,-Two recent Lancet papers have noted that stools from patients with antibiotic-associated colitis contain a toxin which is cytopathic in tissue culture.8,9 The cytopathic effects of the toxin were neutralised with Clostridium sordellii antitoxin. The conclusion is that Cl,. sordellii is responsible for antibiotic-associated colitis. 1. 2. 3. 4. 5.
Roberts, S. H., James, O., Jarvis, G. H. Lancet, 1977, ii, 1193. Gracey, M. Gut, 1971, 12, 403. Scott, A. J., Khan, G. A. ibid. 1968, 9, 187. Gracey, M., Burke, V., Anderson, C. M. Lancet, 1969, ii, 384. Gracey, M., Suharjono, Sunoto, Stone, D. E. Am. J. clin. Nutr. 1973, 26,
1170. 6. Heyworth, B., Brown, J. Archs. Dis. Childh. 1975, 50, 27. 7. Vantrappen, G., Janssens, J., Hellemans, J., Ghoos, Y. J. clin. Invest.
59, 1158. 8. Rifkin, G. D., Fekety, F. R., Silva, J. Jr. Lancet, 9. Larson, H. E., Price, A. B. ibid. p. 1312.
1977, ii, 1103.
1977,
Similar results have been noted in our laboratory using Cl. sordellii antitoxin to neutralise colitis toxin. However, we have been reluctant to ascribe a pathogenic role to this organism because Cl. sordellii has not been recovered in stool cultures by us or by others,8,9 because intracoccal injections of reference strains of Cl. sordellii kill hamsters but necropsies reveal no intestinal lesions, and because the cell-free supernatant of toxinproducing Cl. sordellii strains fail to produce cytotoxicity in tissue culture. Wel0,l1 have found another clostridial species which seems to satisfy these criteria. Cultures of stools from patients with antibiotic-associated colitis yielded Cl. difficile, an organism which is rarely encountered in the normal flora of healthy persons. Broth cultures of these isolates injected intracxcally into hamsters caused an enterocolitis which simulates the anatomical features of the disease encountered clinically. Furthermore, the cell-free supernatant of the Cl. difficile isolates are cytopathic in tissue culture and cytotoxicity is neutralised when the broth supernatants of these strains are mixed with either gasgangrene polyvalent antitoxin or Cl. sordellii antitoxin.’ Our conclusion is that Cl. sordellii antitoxin does indeed neutralise the toxin found in stools from patients with antibiotic-associated colitis. However, this may represent antigenic cross-reactivity between clostridial toxins. Other clostridial species may cause this disease, but the weight of evidence strongly supports the pathogenic role of Cl. difficile. Infectious Disease Research Laboratory, Boston Veterans Administration Hospital, and Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts, U.S.A.
JOHN G. BARTLETT TEWEN CHANG ANDREW B. ONDERDONK
TREATMENT OF ANTIBIOTIC-INDUCED COLITIS BY METRONIDAZOLE
SIR,-Rifkin et al.’ and Dr Modigliani and Dr Delchier (Jan. 14, p. 97) described cases of antibiotic-induced colitis which responded rapidly to oral vancomycin. Your editorial2 prompted us to try metronidazole therapy in a case of severe ampicillin-induced colitis. The patient was a 27-year-old woman, without a history of gastrointestinal disease. 3 days before becoming ill, she had finished a 7-day course of ampicillin (2g/day) for bronchitis. She had colicky abdominal pain, frequent bowel movements, vomiting, and fever (40 °C), which were followed by asthenia, anorexia and mild weight loss. Abdominal signs and fever persisted for 10 days before she was admitted. On examination, the patient was moderately dehydrated and had a distended, tender abdomen. Serum-sodium was 125 mmol/l, hxmoglobin was 9 g/dl, and serum-albumin was 2.2 g/dl. Proctosigmoidoscopy showed numerous yellow-white plaques with intervening normal mucosa. Biopsy confirmed the diagnosis of pseudomembranous colitis. Barium enema showed that the whole colonic wall had a thumb-print pattern. Qualitative stool culture revealed Clostridium perfringens, Cl. butyricum, Bacteroides species, and normal aerobic flora. The patient’s general condition improved after 5 days water-electrolyte replacement and low-residue diet, but diarrhoea persisted with 8-10 liquid, malodorous stools per day. After metronidazole (1-3 g/day) was given, this improved to 3,2, and 1 soft stools/day after 24 h, 48 h, and 72 h treatment, respectively. Proctosigmoidoscopy done 7 days later showed a normal mucosa, confirmed by biopsy, and a second barium enema showed a normal mucosal pattern with only light residual motor disturbances. Metronidazole was 10. Bartlett, J. G., Change, T. W., Gurwith, M., Gorbach, S. L., Onderdonk, A. B. New Engl. J. Med. (in the press). 11. Bartlett, J. G., Onderdonk, A. B., Cisneros, R. L., Kasper, D. L. J. infect. Dis. 1977, 136, 701. 1. Rifkin, G. D., Fekety, F. R., Silva, J., Sack, R. B. Lancet, 1977, ii, 1103.
2. ibid. p. 1113.