Use of alternative or adjuvant pharmacologic treatment strategies in the prevention and treatment of Clostridium difficile infection

Abstract

Infection with Clostridium difficile is currently the leading cause of infectious diarrhea in hospitalized patients, and recent surveillance data indicate that C. difficile has surpassed methicillin-resistant Staphylococcus aureus as the number one cause of hospital-acquired infections in some areas of the USA. In addition, concern over C. difficile has increased over the past decade due to the appearance of new hypervirulent strains. Metronidazole and vancomycin have remained the treatments of choice for initial therapy of primary infection with C. difficile for the past 25 years, but the persistence of spores leads to a recurrence of infection in an estimated 20-25% of patients. Patients who have one recurrent episode have up to a 65% chance of having additional recurrence. While the judicious use of antimicrobials in accordance with antibiotic stewardship guidelines remains the most effective method for the control of C. difficile, the high recurrence rate, increasing incidence, and changing epidemiology of C. difficile has led to an increased interest in the study of alternative strategies for the prevention and treatment of C. difficile disease. These alternative strategies attempt to eliminate C. difficile spores, replenish the normal gut flora, reduce the C. difficile toxin load in the bowel, or bolster the patient's own immune response to the C. difficile toxins. To evaluate the available evidence on these alternative strategies, we conducted a literature search of MEDLINE (1966-March 2011) and International Pharmaceutical Abstracts (1970-March 2011). Available citations from these articles were also utilized. The aim of this review is to summarize the available evidence for alternative treatment strategies for C. difficile disease and to make recommendations for their place in therapy.

Fecal microbiota transplantation in relapsing Clostridium difficile infection

“…A long-term, follow-up, multicenter study of interventional colonoscopic FMT for recurrent CDI has demonstrated a primary cure rate of 91% (defined as the resolution of symptoms without recurrence within 90 days of FMT), and a secondary cure rate of 98% (defined as the resolution of symptoms after one further course of vancomycin with or without repeat FMT) [Brandt et al 2012], whereas traditional methods of antibiotic retreatment without FMT have less efficacy [Musgrave et al 2011]. In conventional treatment, once the initial antibiotic course has been completed, recurrence occurs in 6-50% of the time [Aslam et al 2005;Cohen et al 2010;Pepin et al 2005aPepin et al , 2005b, and after one recurrence incident, patients have up to 65% risk of a subsequent episode of CDI [McFarland, 1998;McFarland et al 2002].…”

Principles of DNA-Based Gut Microbiota Assessment and Therapeutic Efficacy of Fecal Microbiota Transplantation in Gastrointestinal Diseases

“…Continued disruption of the normal colonic microflora by repeated cycles of antibiotic therapy used to treat recurrent CDI perpetuates the risk of repeated recurrences. Forty to 45% of them has a second recurrence, and after 2 or 3 recurrences, 60-65% of the patients have multiple recurrences [23,24,27,28]. The recurrence of CDI is difficult to treat, even with pulsed or tapered antibiotic (principally vancomycin-based) regimens.…”

Actualidades en terapéutica: nuevos antibacterianos

“…• Inhibición de la liberación de las toxinas: se podría decir que este mecanismo ha sido aplicado décadas atrás, utilizando colestiramina en la diarrea por para disminuir la sintomatología en la enfermedad leve [99,100,101]. La colestiramina intercambia un ión cloruro y forma un complejo no absorbible con la toxina en el tracto intestinal [99,100].…”

“…La colestiramina intercambia un ión cloruro y forma un complejo no absorbible con la toxina en el tracto intestinal [99,100]. Recientemente, el sistema de secreción tipo III (T3SS) ha cobrado interés, ya q común a bacterias como Yersinia aeruginosa, E. coli, Shigella spp., spp.…”

“…En la directa, se bloquea directamente la toxina (por ejemplo, el uso de antitoxinas); en la indirecta se modula la respuesta del hospedero ante la toxina (por ejemplo, la inhibición de los canales de cloruro en el tratamiento de la diarrea por Inhibición de la liberación de las toxinas: se podría decir que este mecanismo ha sido aplicado décadas atrás, utilizando colestiramina en la diarrea por C. difficile ntomatología en la enfermedad leve [99,100,101]. La colestiramina intercambia un ión cloruro y forma un complejo no absorbible con la toxina en el tracto intestinal [99,100]. Recientemente, el sistema de secreción tipo III (T3SS) ha cobrado interés, ya que es Yersinia spp., P.…”