New agents for clostridium difficile-associated disease

Expert Opinion on Investigational Drugs

Volumn 17, Issue 11, 2008, Pages 1671-1683

  Guiles, Joseph ^a   Critchley, Ian ^a   Sun, Xicheng ^a  

^a Replidyne Inc   (United States)

Author keywords

CDA 1; CDAD; Clostridium difficile; Fusidic acid; MDX 1388; Nitazoxanide; OPT 80; Oritavancin; Ramoplanin; REP3123; Rifalazil; Rifampin; Rifaximin; Tolevamer; Toxoid

Indexed keywords

ACTIMEL; ANTIBIOTIC AGENT; ANTIINFECTIVE AGENT; BACTERIAL VACCINE; CLINDAMYCIN; CLOSTRIDIUM DIFFICILE TOXOID VACCINE; DANACTIVE; FUSIDIC ACID; METRONIDAZOLE; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY MDX 066; MONOCLONAL ANTIBODY MDX 1388; MOXIFLOXACIN; NITAZOXANIDE; ORITAVANCIN; PLACEBO; POLYPEPTIDE ANTIBIOTIC AGENT; PROBIOTIC AGENT; QUINOLINE DERIVED ANTIINFECTIVE AGENT; RAMOPLANIN; REP 3123; RIFALAZIL; RIFAMYCIN; RIFAXIMIN; TIACUMICIN B; TOLEVAMER; UNCLASSIFIED DRUG; VANCOMYCIN;

ABSENCE OF SIDE EFFECTS; ANTIBIOTIC THERAPY; BACTERIAL INFECTION; CLINICAL PROTOCOL; CLINICAL TRIAL; CLOSTRIDIUM DIFFICILE; COLITIS; COLON RESECTION; DISEASE SEVERITY; DISTRIBUTION VOLUME; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG ELIMINATION; DRUG EXCRETION; DRUG HALF LIFE; DRUG MECHANISM; DRUG MEGADOSE; DRUG POTENCY; DRUG SAFETY; DRUG TOLERABILITY; HUMAN; INCIDENCE; LOW DRUG DOSE; MINIMUM INHIBITORY CONCENTRATION; MORBIDITY; NONHUMAN; PRESCRIPTION; RECOMMENDED DRUG DOSE; RELAPSE; REVIEW; SINGLE DRUG DOSE;

ANIMALS; ANTI-BACTERIAL AGENTS; CLOSTRIDIUM DIFFICILE; DRUG EVALUATION, PRECLINICAL; ENTEROCOLITIS, PSEUDOMEMBRANOUS; HUMANS; PRODRUGS;

EID: 54949141851     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.17.11.1671     Document Type: Review

References (109)

1. Hall IC, O'Toole E. Intestinal flora of new-born infants. Am J Dis Child 1935;49:390-402
2. Bartlett JG, Chang T, Taylor NS, Onderdonk AB. Colitis induced by Clostridium difficile. Rev Infect Dis 1979;1:370-8
3. Kyne L, Farrell RJ, Kelly CP. Clostridium difficile. Gastroenterol Clin North Am 2001;30:753
4. Bartlett JG. Antimicrobial agents implicated in Clostridium difficile toxin-associated diarrhea of colitis. Johns Hopkins Med J 1981;149:6-9
5. Donskey CJ. The role of the intestinal tract as a reservoir and source for transmission of nosocomial pathogens. Clin Infect Dis 2004;39:219-26
6. McFarland LV. Normal flora: diversity and functions. Microb Ecol Health D 2000;12:193-207
7. McFarland LV, Mulligan ME, Kwok RY, Stamm WE. Nosocomial acquisition of Clostridium difficile infection. N Engl J Med 1989;320:204-10
8. Olson MM, Shanholtzer CJ, Lee JT Jr, Gerding DN. Ten years of prospective Clostridium difficile-associated disease surveillance and treatment at the Minneapolis VA Medical Center, 1982-1991. Infect Control Hosp Epidemiol 1994;15:371-81
9. Johnson S, Clabots CR, Linn FV, et al. Nosocomial Clostridium difficile colonisation and disease. Lancet 1990;336:97-100
10. Riley TV, O'Neill GL, Bowman RA, Golledge CL. Clostridium difficile-associared diarrhoea. epidemiological data from Western Australia. Epidemiol Infect 1994;113:13-20
11. McDonald LC, Owings M, Jernigan DB. Clostridium difficile infection in patients discharged from US short-stay hospitals, 1996-2003. Emerg Infect Dis 2006;3:409-15
12. McFarland LV, Beneda HW, Clarridge JE, Raugi GJ. Implications of the changing face of Clostridium difficile disease for health care practitioners. Am J Infect Control 2007;35(4):237-53
13. Shek FW, Stacey BS, Rendell J, et al. The rise of Clostridium difficile: the effect of length of stay, patient age and antibiotic use. J Hosp Infect 2000;45:235-7
14. Riley TV, Codde JP, Rouse IL. Increased length of hospital stay due to Clostridium difficile-associated diarrhoea. Lancet 1995;345(8947):455-6
15. Kyne L, Hamel MB, Polavaram R, Kelly CP. Health care costs and mortality associated with nosocomial diarrhea due to Clostridium difficile. Clin Infect Dis 2002;34(3):346-53
16. McDonald LC, Killgore GE, Thompson A, et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med 2005;353(23):2433-41
17. Zilberberg MD, Shorr AF, Kollef MH. Increase in adult Clostridium difficile-related hospitalizations and case-fatality rate, United States, 2000-2005. Emerg Infect Dis 2008;14(6):929-31
18. Redelings MD, Sorvillo F, Mascola L. Increase in Clostridium difficile-related mortality rates, United States, 1999-2004. Emerg Infect Dis 2007;13(9):1417-9
19. Ryan KJ, Falkow S. Enterbacteriaceae. In: Ryan KJ, editor, Medical microbiology: an introduction to infectious diseases. 3rd edition. New Jersey: McGraw-Hill; 2004; p. 321-44
20. Russmann H, Panthel K, Bader R-C, et al. Evaluation of three rapid assays for detection of Clostridium difficile toxin A and toxin B in stool specimens. Eur J Clin Micro 2007;5:115-9
21. Owens RC. Clostridium difficile-associated disease: an emerging threat to patient safety: insights from the Society of Infectious Diseases Pharmacists. Pharmacotherapy 2006;26(3):299-311
22. Loo VG, Poirier L, Miller MA, et al. A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med 2005;353(23):2442-9
23. Barth H, Aktories K, Popoff MR, Stiles BG. Binary bacterial toxins: biochemistry, biology, and applications of common Clostridium and Bacillus proteins. Microbiol Mol Biol Rev 2004;68(3):373-402, table
24. Owens RC, Valenti AJ. Clostridium difficile-associated disease in the new millennium: 'The perfect storm' has arrived. Infect Dis Clin Pract 2007;15(5):299-315
25. Bartlett JG. Treatment of antibiotic-associated pseudomembranous colitis. Rev Infect Dis 1984;6(Suppl 1):S235-41
26. Teasley DG, Gerding DN, Olson MM, et al. Prospective randomised trial of metronidazole versus vancomycin for Clostridium-difficile-associated diarrhoea and colitis. Lancet 1983;2(8358):1043-6
27. American Society of Health-System Pharmacists: ASHP therapeutic position statement on the preferential use of metronidazole for the treatment of Clostridium difficile-associated disease. Am J Health Syst Pharm 1998;55(13):1407-11
28. Centers for Disease Control. Recommendations for preventing the spread of vancymycin resistance, Recommendations of the Hospital Infection Control Practices Advisory Committee (HICPAC). MMWR 1995;44(No. RR-12):1-20
29. Bourgault AM, Lamothe F, Loo VG, Poirier L. In vitro susceptibility of Clostridium difficile clinical isolates from a multi-institutional outbreak in Southern Quebec, Canada. Antimicrob Agents Chemother 2006;50(10):3473-5
30. Gerding DN. Metronidazole for Clostridium difficile-associated disease: is it okay for Mom? Clin Infect Dis 2005;40(11):1598-600
31. Bricker E, Garg R, Nelson R, et al. Antibiotic treatment for Clostridium difficile-associated diarrhea in adults. Cochrane Database Syst Rev 2005;CD004610
32. Barbut F, Decre D, Burghoffer B, et al. Antimicrobial susceptibilities and serogroups of clinical strains of Clostridium difficile isolated in France in 1991 and 1997. Antimicrob Agents Chemother 1999;43(11):2607-11
33. Biavasco F, Manso E, Varaldo PE. In vitro activities of ramoplanin and four glycopeptide antibiotics against clinical isolates of Clostridium difficile. Antimicrob Agents Chemother 1991;35(1):195-7
34. Cheng SH, Chu FY, Lo SH, Lu JJ. Antimicrobial susceptibility of Clostridium difficile by E test. J Microbiol Immunol Infect 1999;32(2):116-20
35. Dzink J, Bartlett JG. In vitro susceptibility of Clostridium difficile isolates from patients with antibiotic-associated diarrhea or colitis. Antimicrob Agents Chemother 1980;17(4):695-8
36. Jamal WY, Mokaddas EM, Verghese TL, Rotimi VO. In vitro activity of 15 antimicrobial agents against clinical isolates of Clostridium difficile in Kuwait. Int J Antimicrob Agents 2002;20(4):270-4
37. Marchese A, Salerno A, Pesce A, et al. In vitro activity of rifaximin, metronidazole and vancomycin against Clostridium difficile and the rate of selection of spontaneously resistant mutants against representative anaerobic and aerobic bacteria, including ammonia-producing species. Chemotherapy 2000;46(4):253-66
38. Wong SS, Woo PC, Luk WK, Yuen KY. Susceptibility testing of Clostridium difficile against metronidazole and vancomycin by disk diffusion and Etest. Diagn Microbiol Infect Dis 1999;34(1):1-6
39. Wallace JF, Smith RH, Petersdorf RG. Oral administration of vancomycin in the treatment of staphylococcal enterocolitis. N Engl J Med 1965;272:1014-5
40. Musher DM, Aslam S, Logan N, et al. Relatively poor outcome after treatment of Clostridium difficile colitis with metronidazole. Clin Infect Dis 2005;40(11):1586-90
41. Fekety R, Shah AB. Diagnosis and treatment of Clostridium difficile colitis. JAMA 1993;269(1):71-5
42. Pepin J, Routhier S, Gagnon S, Brazeau I. Management and outcomes of a first recurrence of Clostridium difficile-associated disease in Quebec, Canada. Clin Infect Dis 2006;42(6):758-64
43. Gerard L, Garey KW, Dupont HL. Rifaximin: a nonabsorbable rifamycin antibiotic for use in nonsystemic gastrointestinal infections. Expert Rev Antiinfect Ther 2005;3(2):201-11
44. Lagrotteria D, Holmes S, Smieja M, et al. Prospective, randomized inpatient study of oral metronidazole versus oral metronidazole and rifampin for treatment of primary episode of Clostridium difficile-associated diarrhea. Clin Infect Dis 2006;43(5):547-52
45. Scarpignato C, Pelosini I. Rifaximin, a poorly absorbed antibiotic: pharmacology and clinical potential. Chemotherapy 2005;51(Suppl 1):36-66
46. Gerding DN, Johnson S, Osmolski JR, et al. In vitro activity of ramoplanin, rifalazil, rifaximin, metronidazole, and vancomycin against 110 unique toxigenic clostridium difficile clinical isolates. 45th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy 2005; Washington, DC: American Society for Microbiology; December 16-19 2005 E-1439 p171
47. Kokkotou E, Moss AC, Michos A, et al. Comparative efficacies of rifaximin and vancomycin for treatment of Clostridium difficile-associated diarrhea and prevention of disease recurrence in hamsters. Antimicrob Agents Chemother 2008;52(3):1121-6
48. Hecht DW, Galang MA, Sambol SP, et al. In vitro activities of 15 antimicrobial agents against 110 toxigenic Clostridium difficile clinical isolates collected from 1983 to 2004. Antimicrob Agents Chemother 2007;51(8):2716-9
49. O'Connor JR, Galang MA, Sambol SP, et al. Rifampin and rifamixin resistance in clinical isolates of Clostridium difficile. Antimicrob Agents Chemother 2008;52(8):2813-7
50. Boero M, Berti E, Morgando A, Verme G. Terapia della coite da Clostridium difficile: risultati di uno studio randomizzato aperto rifaximina vs. vancomicinia. Microbiol Med 1990;5(2):74-7
51. Johnson S, Schriever C, Galang M, et al. Interruption of recurrent Clostridium difficile-associated diarrhea episodes by serial therapy with vancomycin and rifaximin. Clin Infect Dis 2007;44(6):846-8
52. Cavalleri B, Pagani H, Volpe G, et al. A-16686, a new antibiotic from Actinoplanes. I. Fermentation, isolation and preliminary physico-chemical characteristics. J Antibiot (Tokyo) 1984;37(4):309-17
53. Pallanza R, Berti M, Scotti R, et al. A-16686, a new antibiotic from Actinoplanes. II. Biological properties. J Antibiot (Tokyo) 1984;37(4):318-24
54. Citron DM, Merriam CV, Tyrrell KL, et al. In vitro activities of ramoplanin, teicoplanin, vancomycin, linezolid, bacitracin, and four other antimicrobials against intestinal anaerobic bacteria. Antimicrob Agents Chemother 2003;47(7):2334-8
55. Farver DK, Hedge DD, Lee SC. Ramoplanin: a lipoglycodepsipeptide antibiotic. Ann Pharmacother 2005;39(5):863-8
56. Pullman J, Prieto J, Leach TS. Ramoplanin vs vancomycin in the treatment of C. difficile diarrhea: a phase 2 study. 44th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy 2004; Washington, DC: American Society for Microbiology
57. Theriault RJ, Karwowski JP, Jackson M, et al. Tiacumicins, a novel complex of 18-membered macrolide antibiotics. I. Taxonomy, fermentation and antibacterial activity. J Antibiot (Tokyo) 1987;40(5):567-74
58. Sergio S, Pirali G, White R, Parenti F. Lipiarmycin, a new antibiotic from Actinoplanes III. Mechanism of action. J Antibiot (Tokyo) 1975;28(7):543-9
59. Swanson RN, Hardy DJ, Shipkowitz NL, et al. In vitro and in vivo evaluation of tiacumicins B and C against Clostridium difficile. Antimicrob Agents Chemother 1991;35(6):1108-11
60. Okumu F, Walsh RB, Sears P, Shue YK. Safety and pharmacokinetics of OPT-80, a novel antibiotic for treatment of Clostridium difficle associated Diarrhea (CDAD). 44th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy 2004; Washington, DC; F-726 p204
61. Ackermann G, Loffler B, Adler D, Rodloff AC. In vitro activity of OPT-80 against Clostridium difficile. Antimicrob Agents Chemother 2004;48(6):2280-2
62. Finegold SM, Molitoris D, Vaisanen ML, et al. In vitro activities of OPT-80 and comparator drugs against intestinal bacteria. Antimicrob Agents Chemother 2004;48(12):4898-902
63. Shangle S, Lee C, Okumu F, et al. Safety and pharmacokinetics of OPT-80 in human volunteers. 44th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy 2004; Washington, DC: American Society for Microbiology, abstract A-5 1
64. Louie T, Miller M, Donskey CJ. Safety, pharmacokinetics and outcomes of PAR-101 in healthy subjects and patients with Clostridium difficile-associated diarrhea (CDAD). 45th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy 2005; Washington, DC: American Society for Microbiology, LB2-29
65. Fox LM, Saravolatz LD. Nitazoxanide: a new thiazolide antiparasitic agent. Clin Infect Dis 2005;40(8):1173-80
66. White CA Jr. Nitazoxanide: a new broad spectrum antiparasitic agent. Expert Rev Antiinfect Ther 2004;2(1):43-9
67. Dubreuil L, Houcke I, Mouton Y, Rossignol JF. In vitro evaluation of activities of nitazoxanide and tizoxanide against anaerobes and aerobic organisms. Antimicrob Agents Chemother 1996;40(10):2266-70
68. McVay CS, Rolfe RD. In vitro and in vivo activities of nitazoxanide against Clostridium difficile. Antimicrob Agents Chemother 2000;44(9):2254-8
69. Broekhuysen J, Stockis A, Lins RL, et al. Nitazoxanide: pharmacokinetics and metabolism in man. Int J Clin Pharmacol Ther 2000;38(8):387-94
70. Musher DM, Logan N, Hamill RJ, et al. Nitazoxanide for the treatment of Clostridium difficile colitis. Clin Infect Dis 2006;43(4):421-7
71. Odenholt I, Walder M, Wullt M. Pharmacodynamic studies of vancomycin, metronidazole and fusidic acid against Clostridium difficile. Chemotherapy 2007;53(4):267-74
72. Cronberg S, Castor B, Thoren A. Fusidic acid for the treatment of antibiotic-associated colitis induced by Clostridium difficile. Infection 1984;12(4):276-9
73. Wenisch C, Parschalk B, Hasenhundl M, et al. Comparison of vancomycin, teicoplanin, metronidazole, and fusidic acid for the treatment of Clostridium difficile-associated diarrhea. Clin Infect Dis 1996;22(5):813-8
74. Wullt M, Odenholt. A double-blind randomized controlled trial of fusidic acid and metronidazole for treatment of an initial episode of Clostridium difficile-associated diarrhoea. J Antimicrob Chemother 2004;54(1):211-6
75. Noren T, Wullt M, Akerlund T, et al. Frequent emergence of resistance in Clostridium difficile during treatment of C. difficile-associated diarrhea with fusidic acid. Antimicrob Agents Chemother 2006;50(9):3028-32
76. Babcock GJ, Broering TJ, Hernandez HJ, et al. Human monoclonal antibodies directed against toxins A and B prevent Clostridium difficile-induced mortality in hamsters. Infect Immun 2006;74(11):6339-47
77. Kotloff KL, Wasserman SS, Losonsky GA, et al. Safety and immunogenicity of increasing doses of a Clostridium difficile toxoid vaccine administered to healthy adults. Infect Immun 2001;69(2):988-95
78. Sougioultzis S, Kyne L, Drudy D, et al. Clostridium difficile toxoid vaccine in recurrent C. difficile-associated diarrhea. Gastroenterology 2005;128(3):764-70
79. Seal D, Borriello SP, Barclay F, et al. Treatment of relapsing Clostridium difficile diarrhoea by administration of a non-toxigenic strain. Eur J Clin Microbiol 1987;6(1):51-3
80. Pochapin M. The effect of probiotics on Clostridium difficile diarrhea. Am J Gastroenterol 2000;95(1 Suppl):S11-3
81. Wullt M, Hagslatt ML, Odenholt I. Lactobacillus plantarum 299v for the treatment of recurrent Clostridium difficile-associated diarrhoea: a double-blind, placebo-controlled trial. Scand J Infect Dis 2003;35(6-7):365-7
82. Dendukuri N, Costa V, McGregor M, Brophy JM. Probiotic therapy for the prevention and treatment of Clostridium difficile-associated diarrhea: a systematic review. CMAJ 2005;173(2):167-70
83. McFarland LV. Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. Am J Gastroenterol 2006;101:812-22
84. Doron SI, Hibberd PL, Gorbach SL. Probiotics for prevention of antibiotic-associated diarrhea. J Clin Gastroenterol 2008;42(2):S58-63
85. Braunlin W, Xu Q, Hook P, et al. Toxin binding of tolevamer, a polyanionic drug that protects against antibiotic-associated diarrhea. Biophys J 2004;87(1):534-9
86. Kurtz CB, Cannon EP, Brezzani A, et al. GT160-246, a toxin binding polymer for treatment of Clostridium difficile colitis. Antimicrob Agents Chemother 2001;45(8):2340-7
87. Louie TJ, Peppe J, Watt CK, et al. Tolevamer, a novel nonantibiotic polymer, compared with vancomycin in the treatment of mild to moderately severe Clostridium difficile-associated diarrhea. Clin Infect Dis 2006;43(4):411-20
88. Bouza E, Dryden M, Mohammed R, et al. Results of a phase 3 trial comparing tolevamer, vancomycin and metronidazole in patients with clostridium difficile-associated diarrhoea (CDAD). 18th European Congress of Clinical Microbiology and Infectious Diseases 2008; Apr 19; Barcelona, Spain: European Society of clinical Microbiology and Infectious Diseases
89. McCay GA, Fadhil I, Beaulieu S, et al. Oritavancin disrupts transmembrane potential and membrane integrity concomitantly with cell killing in Staphylococcus aureus and vancomycin-resistant enterococci. 46th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy 2006; San Francisco, CA. American Society for Microbiology. C1-682, p76
90. Arhin FF, Sarmiento I, Parr TR, Moeck G. Mechanisms of action of oritvancin in Staphylococcus aureus. 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy 2007; Chicago, IL. American Society for Microbiology. C1-1471, p85
91. Grover PK, Draghi DC, Moeck G, et al. In vitro activity profile of oritavancin (ORI) against organisms demonstrating key resistance profiles to other antimicrobial agents. 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy 2007; Chicago, IL. American Society for Microbiology. E-1613, p204
92. Draghi DC, Sahm DF, Arhin FF, Moeck G. Anti-enterococcal activity profile of oritavancin, a potent lipoglycopeptide under development for use against Gram-positive infections. 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy 2007; Chicago, IL. American Society for Microbiology. E-1615, p205
93. Moeck G, Draghi DC, Arhin FF, Sahm DF. In vitrro activity profile of oritavancin against a broad spectrum of aerobic and anaerobic bacterial pathogens. 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy 2007; Chicago, IL. American Society for Microbiology. E-1612, p204
94. O'Connor R, Freeman J, Baines S, Wilcox M. In vitro susceptibility of genotypically distinct Clostridium difficile strains to oritavancin. 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy 2007; Chicago, IL. American Society for Microbiology. E-1618, p206
95. Baines SD, O'Connor R, Saxon K, et al. Comparison of oritavancin vs vancomycin as treatment for clindamycin-induced C. difficle ribotype 027 infection in a human gut mode. 18th European Congress of Clinical Microbiology and Infectious Diseases 2008; Apr 19; Barcelona, Spain: European Society of clinical Microbiology and Infectious Diseases
96. Ochsner UA, Sun X, Jarvis T, et al. Aminoacyl-tRNA synthetases: essential and still promising targets for new anti-infective agents. Expert Opin Investig Drugs 2007;16(5):573-93
97. Guiles J, Sun X, Strong S, et al. Chroman-containing inhibitors of methionyl tRNA synthestate: identification and synthesis of REP3123, a novel Clostridium difficile agent. 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy 2007; Chicago, IL. American Society for Microbiology. F-2112 p 257
98. Green L, Bullard J, Ribble W, et al. REP3123 is a potent and selective inhibitor of methionyl tRNA synthetase from Clostridium difficile. 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy 2007; Chicago, IL. American Society for Microbiology. F-2113 p 257
99. Citron DM, Goldstein EJC. In vitro activity of REP3123 against Clostridium difficle and other anaerobic intestinal bacteria. 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy 2007; Chicago, IL. American Society for Microbiology. F-2117 p 258
100. Ochsner UA, Stone K, Hoang T, et al. REP3123 inhibits toxin production in C, difficile. 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy 2007; Chicago, IL. American Society for Microbiology. F-2119 p258
101. Young CL, Hoang T, Critchley IA, Janjic N. REP3123: a narrow spectrum antibacterial agent that inhibits growth and prevents sporulation in Clostridium difficile (CD). 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy 2007; Chicago, IL. American Society for Microbiology. F-2118 p258
102. Bell SJ, Drolet D, Dean F. et al. Efficacy of novel MetRS inhibitors in a C. difficile hamster model. 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy 2007; Chicago, IL. American Society for Microbiology. F-2120 p259
103. Saito H, Tomioka H, Sato K, et al. In vitro antimycobacterial activities of newly synthesized benzoxazinorifamycins. Antimicrob Agents Chemother 1991;35(3):542-7
104. Luna-Herrera J, Reddy MV, Gangadharam PR. In vitro activity of the benzoxazinorifamycin KRM-1648 against drug-susceptible and multidrug-resistant tubercle bacilli. Antimicrob Agents Chemother 1995;39(2):440-4
105. Rothstein DM, Hartman AD, Cynamon MH, Eisenstein BI. Development potential of rifalazil. Expert Opin Investig Drugs 2003;12(2):255-71
106. Akada JK, Shirai M, Fujii K, et al. In vitro anti-Helicobacter pylori activities of new rifamycin derivatives, KRM-1648 and KRM-1657. Antimicrob Agents Chemother 1999;43(5):1072-6
107. Hirata T, Saito H, Tomioka H, et al. In vitro and in vivo activities of the benzoxazinorifamycin KRM-1648 against Mycobacterium tuberculosis. Antimicrob Agents Chemother 1995;39(10):2295-303
108. Anton PM, O'Brien M, Kokkotou E, et al. Rifalazil treats and prevents relapse of clostridium difficile-associated diarrhea in hamsters. Antimicrob Agents Chemother 2004;48(10):3975-9
109. Hosoe K, Mae T, Konishi E, et al. Pharmacokinetics of KRM-1648, a new benzoxazinorifamycin, in rats and dogs. Antimicrob Agents Chemother 1996;40(12):2749-55