Clostridium difficile: Antikörpertherapie und Impfungen

 

 Buy Article Permissions and Reprints

Abstract

Hospital-acquired Clostridium difficile infections have become much more frequent in recent years. Besides treatment with antibiotics and fecal microbiota transplant, new preventive strategies are available now. Bezlotoxumab is an antibody against toxin B and may reduce the risk of relapse by roughly 10 %. Several vaccine candidates against toxins A and B and surface-associated antigens were immunogenic and are tested in clinical trials to investigate the efficacy and safety.

• Literatur

• 1 Bézay N, Ayad A, Dubischar K. et al. Safety, immunogenicity and dose response of VLA84, a new vaccine candidate against Clostridium difficile, in healthy volunteers. Vaccine 2016; 34: 2585-2592
  CrossrefPubMedGoogle Scholar
• 2 Stausberg J. Epidemiology of Clostridium Difficile Infection. Dtsch Arztebl Int 2015; 112: 345
  PubMedGoogle Scholar
• 3 Hogenauer C, Hammer HF, Krejs GJ. et al. Mechanisms and Management of Antibiotic‐Associated Diarrhea. Clin Infect Dis 1998; 27: 702-710
  CrossrefPubMedGoogle Scholar
• 4 de Bruyn G, Saleh J, Workman D. et al. Defining the optimal formulation and schedule of a candidate toxoid vaccine against Clostridium difficile infection: A randomized Phase 2 clinical trial. Vaccine 2016; 34: 2170-2178
  CrossrefPubMedGoogle Scholar
• 5 Leuzzi R, Adamo R, Scarselli M. Vaccines against Clostridium difficile. Hum Vaccin Immunother 2014; 10: 1466-1477
  CrossrefPubMedGoogle Scholar
• 6 Chen S, Sun C, Wang H. et al. The Role of Rho GTPases in Toxicity of Clostridium difficile Toxins. Toxins (Basel) 2015; 7: 5254-5267
  CrossrefPubMedGoogle Scholar
• 7 Guerrant RL, Brunton LL, Schnaitman TC. et al. Cyclic Adenosine Monophosphate and Alteration of Chinese Hamster Ovary Cell Morphology: a Rapid, Sensitive In Vitro Assay for the Enterotoxins of Vibrio cholerae and Escherichia coli. Infect Immun 1974; 10: 320-327
  CrossrefPubMedGoogle Scholar
• 8 Di Bella S, Ascenzi P, Siarakas S. et al. Clostridium difficile Toxins A and B: Insights into Pathogenic Properties and Extraintestinal Effects. Toxins (Basel) 2016; 8: 134
  CrossrefPubMedGoogle Scholar
• 9 Leuzzi R, Spencer J, Buckley A. et al. Protective Efficacy Induced by Recombinant Clostridium difficile Toxin Fragments. Infect Immun 2013; 81: 2851-2860
  CrossrefPubMedGoogle Scholar
• 10 Karczewski J, Zorman J, Wang S. et al. Development of a recombinant toxin fragment vaccine for Clostridium difficile infection. Vaccine 2014; 32: 2812-2818
  CrossrefPubMedGoogle Scholar
• 11 Seregin SS, Aldhamen YA, Rastall DPW. et al. Adenovirus-based vaccination against Clostridium difficile toxin A allows for rapid humoral immunity and complete protection from toxin A lethal challenge in mice. Vaccine 2012; 30: 1492-1501
  CrossrefPubMedGoogle Scholar
• 12 Bertolo L, Boncheff AG, Ma Z. et al. Clostridium difficile carbohydrates: glucan in spores, PSII common antigen in cells, immunogenicity of PSII in swine and synthesis of a dual C. difficile–ETEC conjugate vaccine. Carbohydr Res 2012; 354: 79-86
  CrossrefPubMedGoogle Scholar
• 13 Mattila E, Anttila VJ, Broas M. et al. A randomized, double-blind study comparing Clostridium difficile immune whey and metronidazole for recurrent Clostridium difficile-associated diarrhoea: Efficacy and safety data of a prematurely interrupted trial. Scand J Infect Dis 2008; 40: 702-708
  CrossrefPubMedGoogle Scholar
• 14 Lowy I, Molrine DC, Leav BA. et al. Treatment with Monoclonal Antibodies against Clostridium difficile Toxins. N Engl J Med 2010; 362: 197-205
  CrossrefPubMedGoogle Scholar
• 15 Matsuoka O, Patel DM, Sasaki S. et al. Safety and immunogenicity of Clostridium difficile toxoid vaccine in Japanese adults. Hum Vaccin Immunother 2018; 14: 322-328
  CrossrefPubMedGoogle Scholar
• 16 Tian JH, Fuhrmann SR, Kluepfel-Stahl S. et al. A novel fusion protein containing the receptor binding domains of C. difficile toxin A and toxin B elicits protective immunity against lethal toxin and spore challenge in preclinical efficacy models. Vaccine 2012; 30: 4249-4258
  CrossrefPubMedGoogle Scholar
• 17 Baliban SM, Michael A, Shammassian B. et al. An Optimized, Synthetic DNA Vaccine Encoding the Toxin A and Toxin B Receptor Binding Domains of Clostridium difficile Induces Protective Antibody Responses In Vivo. Infect Immun 2014; 82: 4080-4091
  CrossrefPubMedGoogle Scholar
• 18 Zhang BZ, Cai J, Yu B. et al. A DNA vaccine targeting TcdA and TcdB induces protective immunity against Clostridium difficile. BMC Infect Dis 2016; 16: 596
  CrossrefPubMedGoogle Scholar
• 19 Sheldon E, Kitchin N, Peng Y. et al. A phase 1, placebo-controlled, randomized study of the safety, tolerability, and immunogenicity of a Clostridium difficile vaccine administered with or without aluminum hydroxide in healthy adults. Vaccine 2016; 34: 2082-2091
  CrossrefPubMedGoogle Scholar
• 20 Hogenesch H. Mechanism of Immunopotentiation and Safety of Aluminum Adjuvants. Front Immunol 2013; 3: 1-13
  PubMedGoogle Scholar
• 21 Rabold D, Espelage W, Abu Sin M. et al. The zoonotic potential of Clostridium difficile from small companion animals and their owners. PLoS One 2018; 13: e0193411
  CrossrefPubMedGoogle Scholar