- Email: [email protected]
Response to Drs. Famularo et al.
AJG – July, 2001
4. Schwan A, Sjolin S, Trottestam U, et al. Relapsing Clostridium difficile enterocolitis cured by rectal infusion of homologous feces. Lancet 1983;2(8354):845. 5. Tvede M, Rask-Madsen J. Bacteriotherapy for chronic relapsing Clostridium difficile diarrhoea in six patients. Lancet 1989;1(8648):1156 – 60. 6. Gustafsson A, Lund-Tonnesen A, Berstad A, et al. Faecal short-chain fatty acids in patients with antibiotic-associated diarrhoea, before and after faecal enema treatment. Scand J Gastroenterol 1998;33:721–7. 7. Borody TJ. “Flora power”—fecal bacteria cure chronic C. difficile diarrhea. Am J Gastroenterol 2000;95:3028 –9 (editorial). 8. Banerjee S, Lamont JT. Non-antibiotic therapy for Clostridium difficile infection. Curr Opin Infect Dis 2000;13: 215–9. 9. Campieri M, Gionchetti P. Probiotics in inflammatory bowel disease: New insight to the pathogenesis of the disease or a possible therapeutic alternative? Gastroenterology 1999;116: 1246 –50. 10. Venturi A, Gionchetti P, Rizzello F, et al. Impact on the composition of the faecal flora by a new probiotic preparation: Preliminary data on maintenance treatment of patients with ulcerative colitis. Aliment Pharmacol Ther 1999;13:1103– 8. 11. Gionchetti P, Rizzello F, Venturi A, et al. Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: A double-blind, placebo-controlled trial. Gastroenterology 2000; 119:305–9. 12. Gionchetti P, Rizzello F, Cifone G, et al. In-vivo effect of a highly concentrated probiotic on IL-10 pelvic pouch tissue levels. Gastroenterology 1999;116:A723 (abstract). 13. Famularo G, De Simone C, Gionchetti P, et al. The role of digestive microflora and probiotics in inflammatory bowel disease. Microb Ecol Health Dis 2000;2(suppl 2):138 – 45. Reprint requests and correspondence: Giuseppe Famularo, Department of Medical Sciences, Ospedale San Camillo, Circonvallazione Gianicolense, 00152 Rome, Italy. Received Dec. 26, 2000; accepted Mar. 5, 2001.
Response to Drs. Famularo et al. TO THE EDITOR: We thank Famularo et al. for their well written and erudite letter and are glad that our case study generated some hypotheses. We agree that the fecal flora of each individual are unique and also that fecal bacteriotherapy (because of this reason) may succeed in some individuals, as it did in our patient, and fail in others. It would be preposterously difficult, however, as suggested by the authors, to determine beforehand the bacterial composition of the fecal enema to be used. It has been said it would take one laboratory technician a lifetime to characterize fully the entire bacterial population of feces. Hyperbole? Perhaps, but the point is made. We did not, as stated by Famularo et al., suggest that fecal enemas are “better” than probiotics for the treatment of Clostridium difficile colitis. Indeed, the future in C. difficile treatment belongs to probiotics, and we look forward to “dissection” of the properties of organisms we administer. Since our previous report we have successfully treated
Letters to the Editor
2263
another patient with a 10-month history of recurrent C. difficile infection resistant to conventional therapies. The patient has been asymptomatic for 5 months with negative C. difficile toxin assays after receiving one fecal instillation donated by her husband. Lawrence J. Brandt, M.D. Seth E. Persky, M.D. Division of Gastroenterology Montefiore Medical Center Bronx, New York Reprint requests and correspondence: Lawrence J. Brandt, M.D., Division of Gastroenterology, Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467. Received Apr. 5, 2001; accepted Apr. 5, 2001.
Response to Drs. Famularo et al. TO THE EDITOR: Persky and Brandt (1) may have generated hypotheses— one reason case reports are published— but did not set out to prove anything, as asserted by Famularo et al. Rather, they alerted us to a mechanism of action of fecal flora that now demands further study to answer the many questions this case report generated. In their letter the authors raise the issue of “fecal heterogeneity” and then state that fecal enemas from different individuals cannot be standardized. No one will disagree with this view, but similarly, it has long been known that blood transfusion cannot be standardized, as different blood groups occur—yet, generally blood transfusions give the same result, and this seems to hold true for fecal enemas. Unlike the authors’ unfounded claims, published reports suggest that feces from subjects A, B, and C are indeed likely to prove effective against Clostridium difficile (2). This is probably because feces possess antibiotic activity, a property that can be abolished by heat treatment (3). Furthermore, rather than failing “in a substantial proportion of a statistically significant sample of patients” or showing a “marginal effectiveness” in C. difficile colitis, the published results are totally opposite. Famularo et al. attempt to support their statement by quoting Bowden et al. (4), Schwan et al. (5), Tvede and Rask-Madsen (6), and Gustafsson et al. (7). Here, the authors need to be taken to task, because upon rereading these papers it is clear that results of fecal bacteriotherapy quoted in these articles are anything but “marginal.” Bowden et al. (4) state in their abstract that “the patients responded dramatically.” In pseudomembranous colitis at the time of Bowden’s series the death rate was around 74% (8). Meanwhile, 13 of 16 patients in Bowden’s series were cured very rapidly, and the three who died may have been cured had the treatment not been delayed. In fact, two of these three did not have a pseudomembrane at death, and one had involvement of the small bowel where a fecal enema did not reach. Schwan and
4. Schwan A, Sjolin S, Trottestam U, et al. Relapsing Clostridium difficile enterocolitis cured by rectal infusion of homologous feces. Lancet 1983;2(8354):845. 5. Tvede M, Rask-Madsen J. Bacteriotherapy for chronic relapsing Clostridium difficile diarrhoea in six patients. Lancet 1989;1(8648):1156 – 60. 6. Gustafsson A, Lund-Tonnesen A, Berstad A, et al. Faecal short-chain fatty acids in patients with antibiotic-associated diarrhoea, before and after faecal enema treatment. Scand J Gastroenterol 1998;33:721–7. 7. Borody TJ. “Flora power”—fecal bacteria cure chronic C. difficile diarrhea. Am J Gastroenterol 2000;95:3028 –9 (editorial). 8. Banerjee S, Lamont JT. Non-antibiotic therapy for Clostridium difficile infection. Curr Opin Infect Dis 2000;13: 215–9. 9. Campieri M, Gionchetti P. Probiotics in inflammatory bowel disease: New insight to the pathogenesis of the disease or a possible therapeutic alternative? Gastroenterology 1999;116: 1246 –50. 10. Venturi A, Gionchetti P, Rizzello F, et al. Impact on the composition of the faecal flora by a new probiotic preparation: Preliminary data on maintenance treatment of patients with ulcerative colitis. Aliment Pharmacol Ther 1999;13:1103– 8. 11. Gionchetti P, Rizzello F, Venturi A, et al. Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: A double-blind, placebo-controlled trial. Gastroenterology 2000; 119:305–9. 12. Gionchetti P, Rizzello F, Cifone G, et al. In-vivo effect of a highly concentrated probiotic on IL-10 pelvic pouch tissue levels. Gastroenterology 1999;116:A723 (abstract). 13. Famularo G, De Simone C, Gionchetti P, et al. The role of digestive microflora and probiotics in inflammatory bowel disease. Microb Ecol Health Dis 2000;2(suppl 2):138 – 45. Reprint requests and correspondence: Giuseppe Famularo, Department of Medical Sciences, Ospedale San Camillo, Circonvallazione Gianicolense, 00152 Rome, Italy. Received Dec. 26, 2000; accepted Mar. 5, 2001.
Response to Drs. Famularo et al. TO THE EDITOR: We thank Famularo et al. for their well written and erudite letter and are glad that our case study generated some hypotheses. We agree that the fecal flora of each individual are unique and also that fecal bacteriotherapy (because of this reason) may succeed in some individuals, as it did in our patient, and fail in others. It would be preposterously difficult, however, as suggested by the authors, to determine beforehand the bacterial composition of the fecal enema to be used. It has been said it would take one laboratory technician a lifetime to characterize fully the entire bacterial population of feces. Hyperbole? Perhaps, but the point is made. We did not, as stated by Famularo et al., suggest that fecal enemas are “better” than probiotics for the treatment of Clostridium difficile colitis. Indeed, the future in C. difficile treatment belongs to probiotics, and we look forward to “dissection” of the properties of organisms we administer. Since our previous report we have successfully treated
Letters to the Editor
2263
another patient with a 10-month history of recurrent C. difficile infection resistant to conventional therapies. The patient has been asymptomatic for 5 months with negative C. difficile toxin assays after receiving one fecal instillation donated by her husband. Lawrence J. Brandt, M.D. Seth E. Persky, M.D. Division of Gastroenterology Montefiore Medical Center Bronx, New York Reprint requests and correspondence: Lawrence J. Brandt, M.D., Division of Gastroenterology, Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467. Received Apr. 5, 2001; accepted Apr. 5, 2001.
Response to Drs. Famularo et al. TO THE EDITOR: Persky and Brandt (1) may have generated hypotheses— one reason case reports are published— but did not set out to prove anything, as asserted by Famularo et al. Rather, they alerted us to a mechanism of action of fecal flora that now demands further study to answer the many questions this case report generated. In their letter the authors raise the issue of “fecal heterogeneity” and then state that fecal enemas from different individuals cannot be standardized. No one will disagree with this view, but similarly, it has long been known that blood transfusion cannot be standardized, as different blood groups occur—yet, generally blood transfusions give the same result, and this seems to hold true for fecal enemas. Unlike the authors’ unfounded claims, published reports suggest that feces from subjects A, B, and C are indeed likely to prove effective against Clostridium difficile (2). This is probably because feces possess antibiotic activity, a property that can be abolished by heat treatment (3). Furthermore, rather than failing “in a substantial proportion of a statistically significant sample of patients” or showing a “marginal effectiveness” in C. difficile colitis, the published results are totally opposite. Famularo et al. attempt to support their statement by quoting Bowden et al. (4), Schwan et al. (5), Tvede and Rask-Madsen (6), and Gustafsson et al. (7). Here, the authors need to be taken to task, because upon rereading these papers it is clear that results of fecal bacteriotherapy quoted in these articles are anything but “marginal.” Bowden et al. (4) state in their abstract that “the patients responded dramatically.” In pseudomembranous colitis at the time of Bowden’s series the death rate was around 74% (8). Meanwhile, 13 of 16 patients in Bowden’s series were cured very rapidly, and the three who died may have been cured had the treatment not been delayed. In fact, two of these three did not have a pseudomembrane at death, and one had involvement of the small bowel where a fecal enema did not reach. Schwan and