Immune-based treatment and prevention ofClostridium difficileinfection

Abstract

Clostridium difficile (C. difficile) causes over 500,000 infections per year in the US, with an estimated 15,000 deaths and an estimated cost of $1-3 billion. Moreover, a continual rise in the incidence of severe C. difficile infection (CDI) has been observed worldwide. Currently, standard treatment for CDI is the administration of antibiotics. While effective, these treatments do not prevent and may contribute to a disease recurrence rate of 15-35%. Prevention of recurrence is one of the most challenging aspects in the field. A better knowledge of the molecular mechanisms of the disease, the host immune response and identification of key virulence factors of C. difficilenow permits the development of immune-based therapies. Antibodies specific for C. difficile toxins have been shown to effectively treat CDI and prevent disease relapse in animal models and in humans. Vaccination has been recognized as the most cost-effective treatment/prevention for CDI. This review will summarize CDI transmission, epidemiology, major virulent factors and highlights the rational and the development of immune-based approaches against this remerging threat.

Oral Immunization with Nontoxigenic Clostridium difficile Strains Expressing Chimeric Fragments of TcdA and TcdB Elicits Protective Immunity against C. difficile Infection in Both Mice and Hamsters

“…No vaccine against CDI is currently licensed. Tremendous efforts have been devoted to developing vaccines targeting both toxins (32)(33)(34). However, vaccines directed only against toxins do not target the cells and spores that transmit the disease.…”

Infection prevention and control of Clostridium difficile: a global review of guidelines, strategies, and recommendations

“…Given its high cost and transient protection, active immunization is currently viewed as a potentially more cost–effective strategy. Both toxoid–based and peptide vaccines are currently under development [101,102]. Another developing area of research is the prevention of recurrent episodes and severe disease outcomes with more effective antibiotics.…”

Enfermedad asociada a Clostridium difficile (EACD) en el Hospital Escuela Universitario y el IHSS. Enero a mayo 2016

“…El primero y más importante es la alteración de la microbiota intestinal normal, generalmente por el uso de antibióticos, especialmente clindamicina, penicilinas, cefalosporinas y recientemente fluoroquinolonas, aunque prácticamente todos los antibióticos tienen el potencial de predisponer a esta infección (Van Kleef et al 2014). El uso extendido de antibióticos se ha asociado a un aumento de resistencia a antimicrobianos y constituye el factor de riesgo más importante para el desarrollo de diarrea asociada a C. difficile (Amy et al 2015).…”