Tolevamer, an anionic polymer, neutralizes toxins produced by the BI/027 strains of Clostridium difficile

Antimicrobial Agents and Chemotherapy

Volumn 52, Issue 6, 2008, Pages 2190-2195

  Hinkson, Paul L ^a   Dinardo, Carol ^a   DeCiero, Daniel ^a   Klinger, Jeffrey D ^a   Barker Jr , Robert H ^a,b  

^a Genzyme Drug Discovery and Development   (United States)

^b GENZYME CORPORATION   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CLOSTRIDIUM DIFFICILE TOXIN A; CLOSTRIDIUM DIFFICILE TOXIN B; CLOSTRIDIUM TOXIN; METRONIDAZOLE; TOLEVAMER; VANCOMYCIN;

ANIMAL CELL; ANTIBIOTIC THERAPY; ARTICLE; BACTERIAL FLORA; BACTERIUM CULTURE; CELL SHAPE; CLOSTRIDIUM DIFFICILE; COLON FLORA; CYTOPATHOGENIC EFFECT; CYTOTOXICITY; DIARRHEA; HUMAN; HUMAN CELL; MONOLAYER CULTURE; NONHUMAN; PRIORITY JOURNAL; SUPERNATANT; TISSUE CULTURE;

ANIMALS; ANTIBODIES, BACTERIAL; BACTERIAL PROTEINS; BACTERIAL TOXINS; CELL LINE, TUMOR; CERCOPITHECUS AETHIOPS; CLOSTRIDIUM DIFFICILE; ENTEROCOLITIS, PSEUDOMEMBRANOUS; ENTEROTOXINS; HUMANS; NEUTRALIZATION TESTS; POLYMERS; VERO CELLS;

EID: 44449135437     PISSN: 00664804     EISSN: None     Source Type: Journal    
DOI: 10.1128/AAC.00041-08     Document Type: Article

References (56)

1. Akerlund, T., B. Svenungsson, A. Lagergren, and L. G. Burman. 2006. Correlation of disease severity with fecal toxin levels in patients with Clostridium difficile-associated diarrhea and distribution of PCR ribotypes and toxin yields in vitro of corresponding isolates. J. Clin. Microbiol. 44:353-358.
2. Archibald, L. K., S. N. Banerjee, and W. R. Jarvis. 2004. Secular trends in hospital-acquired Clostridium difficile disease in the United States, 1987-2001. J. Infect. Dis. 189:1585-1588.
3. Barbut, F., D. Deere, V. Lalande, B. Burghoffer, L. Noussair, A. Gigandon, F. Espinasse, L. Raskine, J. Robert, A. Mangeol, C. Branger, and J. C. Petit. 2005. Clinical features of Clostridium difficile-associated diarrhoea due to binary toxin (actin-specific ADP-ribosyltransferase)-producing strains. J. Med. Microbiol. 54:181-185.
4. Barbut, F., B. Gariazzo, L. Bonne, V. Lalande, B. Burghoffer, R. Luiuz, and J. C. Petit. 2007. Clinical features of Clostridium difficile-associated infections and molecular characterization of strains: results of a retrospective study, 2000-2004. Infect. Control Hosp. Epidemiol. 28:131-139.
5. Barker, R. H., Jr., R. Dagher, D. M. Davidson, and J. K. Marquis. 2006. Tolevamer, a novel toxin-binding polymer: overview of preclinical pharmacology and physiochemical properties. Aliment. Pharmacol. Ther. 24:1525-1534.
6. Borriello, S. P., J. M. Ketley, T. J. Mitchell, F. E. Barclay, A. R. Welch, A. B. Price, and J. Stephen. 1987. Clostridium difficile - a spectrum of virulence and analysis of putative virulence determinants in the hamster model of antibiotic-associated colitis. J. Med. Microbiol. 24:53-64.
7. Braun, M., C. Herholz, R. Straub, B. Choisat, J. Frey, J. Nicolet, and P. Kuhnert. 2000. Detection of the ADP-ribosyltransferase toxin gene (cdtA) and its activity in Clostridium difficile isolates from Equidae. FEMS Microbiol. Lett. 184:29-33.
8. Braunlin, W., Q. Xu, P. Hook, R. Fitzpatrick, J. D. Klinger, R. Burrier, and C. B. Kurtz. 2004. Toxin binding of tolevamer, a polyanionic drug that protects against antibiotic-associated diarrhea. Biophys. J. 87:534-539.
9. Centers for Disease Control and Prevention. 2005. Severe Clostridium difficile-associated disease in populations previously at low risk-four states, 2005. MMWR Morb. Mortal. Wkly. Rep. 54:1201-1205.
10. Chaves-Olarte, E., M. Weidmann, C. Eichel-Streiber, and M. Thelestam. 1997. Toxins A and B from Clostridium difficile differ with respect to enzymatic potencies, cellular substrate specificities, and surface binding to cultured cells. J. Clin. Investig. 100:1734-1741.
11. Curry, S. R., J. W. Marsh, C. A. Muto, M. M. O'Leary, A. W. Pasculle, and L. H. Harrison. 2007. tcdC genotypes associated with severe TcdC truncation in an epidemic clone and other strains of Clostridium difficile. J. Clin. Microbiol. 45:215-221.
12. Drummond, L. J., D. G. Smith, and I. R. Poxton. 2003. Effects of sub-MIC concentrations of antibiotics on growth of and toxin production by Clostridium difficile. J. Med. Microbiol. 52:1033-1038.
13. Dupuy, B., and A. L. Sonenshein. 1998. Regulated transcription of Clostridium difficile toxin genes. Mol. Microbiol. 27:107-120.
14. Eggertson, L., and B. Sibbald. 2004. Hospitals battling outbreaks of C. difficile. CMAJ 171:19-21.
15. Fekety, R., L. V. McFarland, C. M. Surawicz, R. N. Greenberg, G. W. Elmer, and M. E. Mulligan. 1997. Recurrent Clostridium difficile diarrhea: characteristics of and risk factors for patients enrolled in a prospective, randomized, double-blinded trial. Clin. Infect. Dis. 24:324-333.
16. Fekety, R., and A. B. Shah. 1993. Diagnosis and treatment of Clostridium difficile colitis. JAMA 269:71-75.
17. George, W. L., R. D. Rolfe, and S. M. Finegold. 1982. Clostridium difficile and its cytotoxin in feces of patients with antimicrobial agent-associated diarrhea and miscellaneous conditions. J. Clin. Microbiol. 15:1049-1053.
18. Geric, B., R. J. Carman, M. Rupnik, C. W. Genheimer, S. P. Sambol, D. M. Lyerly, D. N. Gerding, and S. Johnson. 2006. Binary toxin-producing, large clostridial toxin-negative Clostridium difficile strains are enterotoxic but do not cause disease in hamsters. J. Infect. Dis. 193:1143-1150.
19. Geric, B., M. Rupnik, D. N. Gerding, M. Grabnar, and S. Johnson. 2004. Distribution of Clostridium difficile variant toxinotypes and strains with binary toxin genes among clinical isolates in an American hospital. J. Med. Microbiol. 53:887-894.
20. Gonçalves, C., D. Decré, F. Barbut, B. Burghoffer, and J.-C. Petit. 2004. Prevalence and characterization of a binary toxin (actin-specific ADP-ribosyltransferase) from Clostridium difficile. J. Clin. Microbiol. 42:1933-1939.
21. Haslam, S. C., J. M. Ketley, T. J. Mitchell, J. Stephen, D. W. Burden, and D. C. A. Candy. 1986. Growth of Clostridium difficile and production of toxins A and B in complex and defined media. J. Med. Microbiol. 21:293-297.
22. Hogenauer, C., H. F. Hammer, G. J. Krejs, and E. C. Reisinger. 1998. Mechanisms and management of antibiotic-associated diarrhea. Clin. Infect. Dis. 27:702-710.
23. Hookman, P., and J. S. Barkin. 2007. Review: Clostridium difficile-associated disorders/diarrhea and Clostridium difficile colitis: the emergence of a more virulent era. Dig. Dis. Sci. 52:1071-1075.
24. Karlsson, S., A. Lindberg, E. Norin, L. G. Burman, and T. Akerlund. 2000. Toxins, butyric acid, and other short-chain fatty acids are coordinately expressed and down-regulated by cysteine in Clostridium difficile. Infect. Immun. 68:5881-5888.
25. Kelly, C. P., C. Pothoulakis, and J. T. LaMont. 1994. Clostridium difficile colitis. N. Engl. J. Med. 330:257-262.
26. Kuijper, E. J., R. J. van den Berg, S. Debast, C. E. Visser, D. Veenendaal, A. Troelstra, T. van der Kooi, S. van den Hof, and D. W. Notermans. 2006. Clostridium difficile ribotype 027, toxinotype III, the Netherlands. Emerg. Infect. Dis. 12:827-830.
27. Kurtz, C. B., E. P. Cannon, A. Brezzani, M. Pitruzzello, C. Dinardo, E. Rinard, D. W. K. Acheson, R. Fitzpatrick, P. Kelly, K. Shackett, A. T. Papoulis, P. J. Goddard, R. H. Barker, Jr., G. P. Palace, and J. D. Klinger. 2001. GT160-246, a toxin binding polymer for treatment of Clostridium difficile colitis. Antimicrob. Agents Chemother. 45:2340-2347.
28. Loo, V. G., L. Poirier, M. A. Miller, M. Oughton, M. D. Libman, S. Michaud, A. M. Bourgault, T. Nguyen, C. Frenette, M. Kelly, A. Vibien, P. Brassard, S. Fenn, K. Dewar, T. J. Hudson, R. Horn, P. Rene, Y. Monczak, and A. Dascal. 2005. A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N. Engl. J. Med. 353:2442-2449.
29. Louie, T. J., M. Gerson, S. Johnson, L. Poirier, K. Weiss, J. Peppe, J. Donovan, and D. Davidson. 2007. Results of a phase III trial comparing tolevamer, vancomycin and metronidazole in patients with Clostridium difficile-associated diarrhea (CDAD), abstr. 425a. Abstr. 47th. Intersci. Conf. Antimicrob. Agents Chemother., Chicago, IL.
30. Louie, T. J., J. Peppe, C. K. Watt, D. Johnson, R. Mohammed, G. Dow, K. Weiss, S. Simon, J. F. John, Jr., G. Garber, S. Chasan-Taber, and D. M. Davidson. 2006. Tolevamer, a novel nonantibiotic polymer, compared with vancomycin in the treatment of mild to moderately severe Clostridium difficile-associated diarrhea. Clin. Infect. Dis. 43:411-420.
31. Lyerly, D. M., D. E. Lockwood, S. H. Richardson, and T. D. Wilkins. 1982. Biological activities of toxins A and B of Clostridium difficile. Infect. Immun. 35:1147-1150.
32. Matamouros, S., P. England, and B. Dupuy. 2007. Clostridium difficile toxin expression is inhibited by the novel regulator TcdC. Mol. Microbiol. 64:1274-1288.
33. McDonald, L. C., G. E. Killgore, A. Thompson, R. C. Owens, Jr., S. V. Kazakova, S. P. Sambol, S. Johnson, and D. N. Gerding. 2005. An epidemic, toxin gene-variant strain of Clostridium difficile. N. Engl. J. Med. 353:2433-2441.
34. McFarland, L. V. 2000. Normal flora: diversity and functions. Microb. Ecol. Health Dis. 12:193-207.
35. McFarland, L. V., G. W. Elmer, W. E. Stamm, and M. E. Mulligan. 1991. Correlation of immunoblot type, enterotoxin production, and cytotoxin production with clinical manifestations of Clostridium difficile infection in a cohort of hospitalized patients. Infect. Immun. 59:2456-2462.
36. Musher, D. M., S. Aslam, N. Logan, S. Nallacheru, I. Bhaila, F. Borchert, and R. J. Hamill. 2005. Relatively poor outcome after treatment of Clostridium difficile colitis with metronidazole. Clin. Infect. Dis. 40:1586-1590.
37. Muto, C. A., M. Pokrywka, K. Shutt, A. B. Mendelsohn, K. Nouri, K. Posey, T. Roberts, K. Croyle, S. Krystofiak, S. Patel-Brown, A. W. Pasculle, D. L. Paterson, M. Saul, and L. H. Harrison. 2005. A large outbreak of Clostridium difficile-associated disease with an unexpected proportion of deaths and colectomies at a teaching hospital following increased fluoroquinolone use. Infect. Control Hosp. Epidemiol. 26:273-280.
38. Nachamkin, I., L. Lotz-Nolan, and D. Skalina. 1986. Evaluation of a commercial cytotoxicity assay for detection of Clostridium difficile toxin. J. Clin. Microbiol. 23:954-955.
39. National Clostridium difficile Standards Group. 2004. National Clostridium difficile Standards Group: report to the Department of Health. J. Hosp. Infect. 56(Suppl. 1):1-38.
40. Onderdonk, A. B., B. R. Lowe, and J. G. Bartlett. 1979. Effect of environmental stress on Clostridium difficile toxin levels during continuous cultivation. Appl. Environ. Microbiol. 38:637-641.
41. Peled, N., S. Pitlik, Z. Samra, A. Kazakov, Y. Bloch, and J. Bishara. 2007. Predicting Clostridium difficile toxin in hospitalized patients with antibiotic-associated diarrhea. Infect. Control Hosp. Epidemiol. 28:377-381.
42. Pepin, J., M. E. Alary, L. Valiquette, E. Raiche, J. Ruel, K. Fulop, D. Godin, and C. Bourassa. 2005. Increasing risk of relapse after treatment of Clostridium difficile colitis in Quebec, Canada. Clin. Infect. Dis. 40:1591-1597.
43. Pepin, J., L. Valiquette, M. E. Alary, P. Villemure, A. Pelletier, K. Forget, K. Pepin, and D. Chouinard. 2004. Clostridium difficile-associated diarrhea in a region of Quebec from 1991 to 2003: a changing pattern of disease severity. CMAJ 171:466-472.
44. Pepin, J., L. Valiquette, and B. Cossette. 2005. Mortality attributable to nosocomial Clostridium difficile-associated disease during an epidemic caused by a hypervirulent strain in Quebec. CMAJ 173:1037-1042.
45. Perelle, S., M. Gibert, P. Bourlioux, G. Corthier, and M. R. Popoff. 1997. Production of a complete binary toxin (actin-specific ADP-ribosyltransferase) by Clostridium difficile CD196. Infect. Immun. 65:1402-1407.
46. Popoff, M. R., E. J. Rubin, D. M. Gill, and P. Boquet. 1988. Actin-specific ADP-ribosyltransferase produced by a Clostridium difficile strain. Infect. Immun. 56:2299-2306.
47. Pothoulakis, C., and J. T. LaMont. 1993. Clostridium difficile colitis and diarrhea. Gastroenterol. Clin. N. Am. 22:623-637.
48. Rupnik, M., V. Avesani, M. Jane, C. von Eichel-Streiber, and M. Delmee. 1998. A novel toxinotyping scheme and correlation of toxinotypes with serogroups of Clostridium difficile isolates. J. Clin. Microbiol. 36:2240-2247.
49. Stubbs, S., M. Rupnik, M. Gibert, J. Brazier, B. Duerden, and M. Popoff. 2000. Production of actin-specific ADP-ribosyltransferase (binary toxin) by strains of Clostridium difficile. FEMS Microbiol. Lett. 186:307-312.
50. Terhes, G., E. Urban, J. Soki, K. A. Hamid, and E. Nagy. 2004. Community-acquired Clostridium difficile diarrhea caused by binary toxin, toxin A, and toxin B gene-positive isolates in Hungary. J. Clin. Microbiol. 42:4316-4318.
51. Torres, J., M. Camorlinga-Ponce, and O. Munoz. 1992. Sensitivity in culture of epithelial cells from rhesus monkey kidney and human colon carcinoma to toxins A and B from Clostridium difficile. Toxicon 30:419-426.
52. Valiquette, L., D. E. Low, J. Pepin, and A. McGeer. 2004. Clostridium difficile infection in hospitals: a brewing storm. CMAJ 171:27-29.
53. van den Berg, R. J., H. A. Ameen, T. Furusawa, E. C. Claas, E. R. van der Vorm, and E. J. Kuijper. 2005. Coexistence of multiple PCR-ribotype strains of Clostridium difficile in faecal samples limits epidemiological studies. J. Med. Microbiol. 54:173-179.
54. Voth, D. E., and J. D. Ballard. 2005. Clostridium difficile toxins: mechanism of action and role in disease. Clin. Microbiol. Rev. 18:247-263.
55. Warny, M., J. Pepin, A. Fang, G. E. Killgore, J. Thompson, J. Brazier, E. Frost, and L. C. McDonald. 2005. Toxin production by an emerging strain of Clostridium difficile associated with outbreaks of severe disease in North America and Europe. Lancet 366:1079-1084.
56. Wren, B. W., S. R. Heard, and S. Tabaqchili. 1987. Association between production of toxins A and B and types of Clostridium difficile. J. Clin. Pathol. 40:1397-1401.