Erika J Goldberg1, Sumit Bhalodia1, Sherin Jacob1, Hatil Patel1, Ken V Trinh1, Blessy Varghese1, Jungmo Yang1, Sean R Young1, Robert B Raffa2. 1. Erika J. Goldberg is a Pharm.D. student; Sumit Bhalodia is a Pharm.D. student; Sherin Jacob is a Pharm.D. student; Hatil Patel is a Pharm.D. student; Ken V. Trinh is a Pharm.D. student; Blessy Varghese is a Pharm.D. student; Jungmo Yang is a Pharm.D. student; Sean R. Young is a Pharm.D. student; and Robert B. Raffa, Ph.D., is Professor, Temple University School of Pharmacy, Philadelphia, PA. 2. Erika J. Goldberg is a Pharm.D. student; Sumit Bhalodia is a Pharm.D. student; Sherin Jacob is a Pharm.D. student; Hatil Patel is a Pharm.D. student; Ken V. Trinh is a Pharm.D. student; Blessy Varghese is a Pharm.D. student; Jungmo Yang is a Pharm.D. student; Sean R. Young is a Pharm.D. student; and Robert B. Raffa, Ph.D., is Professor, Temple University School of Pharmacy, Philadelphia, PA. robert.raffa@temple.edu.
Abstract
PURPOSE: Established and investigational antibiotic, monoclonal antibody, vaccine, and microbe-based approaches to the prevention and treatment of Clostridium difficile infection (CDI) are reviewed. SUMMARY: CDI is increasingly prevalent in the United States and other countries, particularly among hospitalized patients and the elderly, who are at high risk for potentially fatal CDI-related enterotoxic diarrhea. Established therapies for CDI such as vancomycin and metronidazole (an off-label use) are limited by poor efficacy and high recurrence rates. An investigational antibiotic with potent in vitro activity against all C. difficile strains (including the hypervirulent BI/NAP1/027 strain) has yielded encouraging results in early clinical trials. Another promising approach involves the use of monoclonal antibodies with selective activity against toxins responsible for CDI-associated diarrhea; in a small Phase II clinical trial, a single monoclonal antibody infusion in combination with vancomycin or metronidazole therapy was more effective than antibiotic therapy alone in preventing CDI relapse. Other emerging approaches to CDI treatment and prophylaxis include the use of vaccines against C. difficile toxins (several C. difficile-targeted vaccines are under development in Europe and the United States); microbe-based strategies such as fecal microbiota transplants, "microbial ecosystem therapeutics," and probiotic supplements; and an investigational encapsulated form of β-lactamase designed to prevent C. difficile colonization from progressing to CDI. CONCLUSION: The current antibiotic therapies for CDI, mainly vancomycin and (off-label) metronidazole and the newer agent fidaxomicin, have limitations with respect to efficacy, recurrence rates, and adverse effects, but a variety of promising approaches are emerging.
PURPOSE: Established and investigational antibiotic, monoclonal antibody, vaccine, and microbe-based approaches to the prevention and treatment of Clostridium difficile infection (CDI) are reviewed. SUMMARY: CDI is increasingly prevalent in the United States and other countries, particularly among hospitalized patients and the elderly, who are at high risk for potentially fatal CDI-related enterotoxic diarrhea. Established therapies for CDI such as vancomycin and metronidazole (an off-label use) are limited by poor efficacy and high recurrence rates. An investigational antibiotic with potent in vitro activity against all C. difficile strains (including the hypervirulent BI/NAP1/027 strain) has yielded encouraging results in early clinical trials. Another promising approach involves the use of monoclonal antibodies with selective activity against toxins responsible for CDI-associated diarrhea; in a small Phase II clinical trial, a single monoclonal antibody infusion in combination with vancomycin or metronidazole therapy was more effective than antibiotic therapy alone in preventing CDI relapse. Other emerging approaches to CDI treatment and prophylaxis include the use of vaccines against C. difficile toxins (several C. difficile-targeted vaccines are under development in Europe and the United States); microbe-based strategies such as fecal microbiota transplants, "microbial ecosystem therapeutics," and probiotic supplements; and an investigational encapsulated form of β-lactamase designed to prevent C. difficile colonization from progressing to CDI. CONCLUSION: The current antibiotic therapies for CDI, mainly vancomycin and (off-label) metronidazole and the newer agent fidaxomicin, have limitations with respect to efficacy, recurrence rates, and adverse effects, but a variety of promising approaches are emerging.
Authors: Jennifer K Spinler; Aaron Brown; Caná L Ross; Prapaporn Boonma; Margaret E Conner; Tor C Savidge Journal: Anaerobe Date: 2016-05-11 Impact factor: 3.331